Publications by authors named "Alexander Breitenstein"

47 Publications

Snare technique for coronary sinus cannulation in cardiac resynchronization therapy.

Indian Pacing Electrophysiol J 2020 Nov - Dec;20(6):293-295. Epub 2020 Sep 28.

Electrophysiology, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland. Electronic address:

Purpose: Biventricular pacing is a mainstay of therapy for patients with heart failure. However, lead implantations may fail due to anatomical reasons including the impossibility of coronary sinus cannulation.

Methods And Results: A dual approach from the subclavian vein using a snare through a sheath and from the femoral vein using a steerable electrophysiology catheter was performed. Once the snare hooked the catheter, the latter was advanced into the coronary sinus and finally, the sheath could also be advanced in an "over-the-wire" technique.

Conclusion: The snare technique for coronary sinus cannulation offers a "bail-out" strategy for left ventricular lead implantation.
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http://dx.doi.org/10.1016/j.ipej.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691783PMC
September 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

ILEEM-survey on the Heart Team approach and team training for lead extraction procedures.

Cardiol J 2020 Sep 11. Epub 2020 Sep 11.

Green Lane Cardiovascular Service, Auckland City Hospital, and University of Auckland, New Zealand.

Background: The Heart Team approach has become an integral part of modern cardiovascular medicine. To evaluate current opinions and real-world practice among lead extraction practitioners, an online survey was created and distributed among a pool of lead extraction specialists participating in the International Lead Extraction Expert Meeting (ILEEM) 2018.

Methods: The online survey consisted of 10 questions and was performed using an online survey tool (www.surveymonkey.com). The collector link was sent to 48 lead extraction experts via email.

Results: A total of 43 answers were collected (89% return rate) from lead extraction experts in 16 different countries. A great majority (83.7%) of the respondents performed more than 30 lead extraction procedures per year. The most common procedural environment in this survey was the hybrid operating room (67.4%). Most procedures were performed by electrophysiologists and cardiologists (80.9%). Important additional members of the current lead extraction teams were cardiac surgeons (79.1%), anesthesiologists (95.3%) and operating room scrub nurses (76.7%). An extended Heart Team is regarded beneficial for patient care by 86.0%, with potential further members being infectious diseases specialists, intensivists and radiologists. Team training activities are performed in 48.8% of participating centers.

Conclusions: This survey supports the importance of establishing lead extraction Heart Teams in specialized lead extraction centers to potentially improve patient outcomes. The concept of a core and an extended heart team approach in lead extraction procedures is introduced.
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http://dx.doi.org/10.5603/CJ.a2020.0106DOI Listing
September 2020

Familial dilated cardiomyopathy associated with a novel heterozygous RYR2 early truncating variant.

Cardiol J 2020 Aug 4. Epub 2020 Aug 4.

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

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http://dx.doi.org/10.5603/CJ.a2020.0099DOI Listing
August 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

Results of the Patient-Related Outcomes of Mechanical lead Extraction Techniques (PROMET) study: a multicentre retrospective study on advanced mechanical lead extraction techniques.

Europace 2020 07;22(7):1103-1110

Cardiology Clinical Academic Group, St. George's University Hospitals NHS Foundation Trust, London, UK.

Aims: Several large studies have documented the outcome of transvenous lead extraction (TLE), focusing on laser and mechanical methods. To date there has been no large series addressing the results obtained with rotational lead extraction tools. This retrospective multicentre study was designed to investigate the outcomes of mechanical and rotational techniques.

Methods And Results: Data were collected on a total of 2205 patients (age 66.0 ± 15.7 years) with 3849 leads targeted for extraction in six European lead extraction centres. The commonest indication was infection (46%). The targeted leads included 2879 pacemaker leads (74.8%), 949 implantable cardioverter-defibrillator leads (24.6%), and 21 leads for which details were unknown; 46.6% of leads were passive fixation leads. The median lead dwell time was 74 months [interquartile range (IQR) 41-112]. Clinical success was obtained in 97.0% of procedures, and complete extraction was achieved for 96.5% of leads. Major complications occurred in 22/2205 procedures (1%), with a peri-operative or procedure-related mortality rate of 4/2205 (0.18%). Minor complications occurred in 3.1% of procedures. A total of 1552 leads (in 992 patients) with a median dwell time of 106 months (IQR 66-145) were extracted using the Evolution rotational TLE tool. In this subgroup, complete success was obtained for 95.2% of leads with a procedural mortality rate of 0.4%.

Conclusion: Patient outcomes in the PROMET study compare favourably with other large TLE trials, underlining the capability of rotational TLE tools and techniques to match laser methods in efficacy and surpass them in safety.
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http://dx.doi.org/10.1093/europace/euaa103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336182PMC
July 2020

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

Radiother Oncol 2020 Nov 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

Transcatheter aspiration of large pacemaker and implantable cardioverter-defibrillator lead vegetations facilitating safe transvenous lead extraction.

Europace 2020 01;22(1):133-138

Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Augustenburger Platz 1, Berlin, Germany.

Aims: Treatment of patients with systemic cardiac implantable electronic device (CIED) infection with large lead vegetations is challenging and associated with relevant morbidity and mortality. To avoid complications from open surgical extraction, a novel approach with percutaneous aspiration of large vegetations prior to transvenous lead extraction was instituted. The results of this treatment concept were retrospectively analysed in this multicentre study.

Methods And Results: One hundred and one patients [mean age 68.2 ± 13.1 (30-92) years] were treated in four centres for endovascular CIED infection with large lead vegetations. Mean lead vegetation size was 30.7 ± 13.5 mm. Two hundred and forty-seven leads were targeted for extraction (170 pacemaker leads, 77 implantable cardioverter-defibrillator leads). Mean lead implant duration was 81.7 (1-254) months. The transcatheter aspiration system with a specialized long venous drainage cannula and a funnel-shaped tip was based on a veno-venous extracorporeal circuit with an in-line filter. The aspiration of vegetations showed complete procedural success in 94.0% (n = 95), partial success in 5.0% (n = 5). Three major complications (3.0%) were encountered. Complete procedural success (per lead) of the subsequently performed transvenous lead extraction procedure was 99.2% (n = 245). Thirty-day mortality was 3.0% (n = 3). Five patients (5.0%) died in the further course on Days 51, 54, 68, 134, and 182 post-procedure (septic complications: n = 4; heart failure: n = 1).

Conclusion: The percutaneous aspiration procedure is highly effective and is associated with a low complication profile. The aspiration of vegetations immediately prior and during the lead extraction procedure may avoid septic embolization into the pulmonary circulation. This may potentially lead to a long-term survival benefit.
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http://dx.doi.org/10.1093/europace/euz283DOI Listing
January 2020

Extraction of a leadless pacemaker 23 months after implantation.

Eur Heart J 2020 Jun;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

Devices in Heart Failure Patients-Who Benefits From ICD and CRT?

Front Cardiovasc Med 2019 13;6:111. Epub 2019 Aug 13.

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

Despite advances in heart failure treatment, this condition remains a relevant medical issue and is associated with a high morbidity and mortality. The cause of death in patients suffering from heart failure is not only a result of hemodynamic failure, but can also be due to ventricular arrhythmias. Implantable cardioverter defibrillators (ICDs) are these days the only tool to significantly reduce arrhythmic sudden death; but not all patients benefit to the same extend. In addition, cardiac resynchronization therapy (CRT) is another tool which is used in patients suffering from heart fialure. Even though both devices have been investigated in large randomized trials, both ICD and CRT remain underutilized in many countries. This brief review focuses on various aspects in this regard including a short overview on upcoming device novelties in the near future.
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http://dx.doi.org/10.3389/fcvm.2019.00111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700378PMC
August 2019

Fluoroscopy times in electrophysiology and device procedures: impact of single frame location fluoroscopy.

Eur Heart J 2019 03;40(10):857

Department of Cardiology, Barts Heart Centre, West Smithfields, London, UK.

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http://dx.doi.org/10.1093/eurheartj/ehy744DOI Listing
March 2019

A novel technique for performing transseptal puncture guided by a non-fluoroscopic 3D mapping system.

Pacing Clin Electrophysiol 2019 01 28;42(1):4-12. Epub 2018 Nov 28.

Department of Arrhythmia Services, The Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom.

Background: Transseptal puncture (TSP) is commonly performed under fluoroscopic guidance in left atrial ablation procedures. This exposes patients and healthcare professionals to deleterious ionizing radiation. We describe a novel technique for performing TSP non-fluoroscopically using a three-dimensional (3D) mapping system only. The safety and efficacy of this technique is compared to traditional fluoroscopy guided TSP.

Methods: Retrospective, single-center study of patients undergoing TSP for left atrial ablation. Those undergoing TSP using 3D mapping system alone (nonfluoroscopy group) were compared to those undergoing fluoroscopic guided TSP (Fluoroscopy group). Clinical, procedural data and complications were analyzed from a prospective registry.

Results: Twenty patients (32 TSPs) in the nonfluoroscopy (NF) group were compared to 14 patients (25 TSPs) in fluoroscopy (F) group. TSP success rates were similar across the groups (88% vs 96% in the NF and F groups, P = 0.97). In the NF group, there was one cardiac tamponade, two unsuccessful TSPs (previous cardiac surgery-required TOE guided TSP), and one patient required fluoroscopy on a background of CRTD device to avoid lead displacement. The mean fluoroscopy time and dose were significantly lower in the nonfluoroscopy group (0.75  ±  0.50 vs 5.32 ± 3.23 min, P  <  0.001; 92.5 ± 60.7 vs 394.3 ± 182.7 cGy/cm , P < 0.001).

Conclusion: Our study shows that TSPs can be performed safely and effectively using this non-fluoroscopic novel technique in a select group of patients. Radiation exposure is reduced significantly without compromising patient safety. Larger studies are required to substantiate these results. Patients with cardiac implantable devices and previous cardiac surgery may pose a challenge to using this technique.
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http://dx.doi.org/10.1111/pace.13541DOI Listing
January 2019

Ventricular tachycardia ablation in structural heart disease: Impact of ablation strategy and non-inducibility as an end-point on long term outcome.

Int J Cardiol 2019 Feb 1;277:110-117. Epub 2018 Sep 1.

The Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK. Electronic address:

Background: To investigate the long term outcomes after catheter ablation (CA) of ventricular tachycardia (VT) in the context of structural heart disease in a multicenter cohort. The impact of different ablation strategies (substrate ablation versus activation guided versus combined) and non-inducibility as an end-point was evaluated.

Methods: Data was pooled from prospective registries at 5 centres over a 5 year period. Success was defined as survival free from recurrent ventricular arrhythmias (VA). Multivariate analysis of factors predicting survival free from VA was analysed by Cox regression.

Results: Five hundred sixty-six patients underwent CA for VT. Patients were 64 ± 15 years. Left ventricular ejection fraction was 35 ± 15% and 66% had ischaemic heart disease. At 2.3 (IQR 1.0-4.2) years, success was achieved in 44% after a single procedure, rising to 60% after repeat procedures. Mortality at final follow up was 22%. Multivariate analysis showed that higher left ventricular ejection fraction, younger age, ischaemic heart disease, and non-inducibility of VA predicted long term survival free from VA (all p < 0.05). There was no impact of the approach to ablation.

Conclusion: CA eliminates VT in a large proportion of patients long term. Ablation strategy did not impact outcome and hence substrate ablation is a reasonable initial strategy. Non-inducibility of VA predicted survival free from VA and may be worth pursuing as a procedural end-point.
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http://dx.doi.org/10.1016/j.ijcard.2018.08.099DOI Listing
February 2019

Cardiac Resynchronisation Therapy (CRT) Survey II: CRT implantation in Europe and in Switzerland.

Swiss Med Wkly 2018 Aug 22;148:w14643. Epub 2018 Aug 22.

University Hospital Basel, Switzerland.

Aim: Between October 2015 and December 2016, 11,088 patients from 42 countries having cardiac resynchronisation therapy (CRT) devices implanted were included in the CRT II Survey. We compared the characteristics of Swiss CRT recipients with the overall European population.

Methods: Demographic and procedural data from seven Swiss centres recruiting all consecutive patients undergoing either de-novo CRT implantation or an upgrade to a CRT system were collected and compared with the European population.

Results: A total of 320 Swiss patients (24.4% female, mean age 71.0 ± 10.2 years, 47% ischaemic cardiomyopathy) were enrolled, which amounts to 38% of all CRT implantations in Switzerland during this period. Of the patients enrolled, 38% had atrial fibrillation, 27% second- or third-degree atrioventricular block, and 68% complete left bundle-branch block. Swiss patients had significantly less often the classical indication of heart failure with a wide QRS complex (40 vs 61%; odds ratio [OR] 0.44, 95% confidence interval [CI] 0.35-0.55; p <0.001). Compared with the European population, Swiss patients were significantly older (71 vs 68.5 years, p <0.001), less symptomatic from heart failure and had more chronic kidney disease. Swiss patients significantly more often received a CRT-pacemaker (37 vs 30%; OR 1.37; 95% CI 1.09-1.73; p = 0.007) and quadripolar left ventricular leads (69 vs 57%; OR 1.67, 95% CI 1.32-2.13; p <0.001).

Conclusion: Compared with European CRT recipients, Swiss CRT patients are older, less symptomatic and suffer more often from comorbidities. Although two thirds of the implantations were CRT-defibrillator systems, Swiss patients more often received CRT-pacemaker systems than their European counterparts.
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http://dx.doi.org/10.4414/smw.2018.14643DOI Listing
August 2018

Usefulness of a clinical risk score to predict the response to cardiac resynchronization therapy.

Int J Cardiol 2018 06;260:82-87

Clinique Pasteur, Toulouse, France.

Background: Almost 1/3 of heart failure patients fail to respond to cardiac resynchronization therapy (CRT). A simple clinical score to predict who these patients are at the moment of referral or at time of implant may be of importance for early optimization of their management.

Methods: Observational study. A risk score was derived from factors associated to CRT response. The derivation cohort was composed of 1301 patients implanted with a CRT defibrillator in a multi-center French cohort-study. External validation of this score and assessment of its association with CRT response and all-cause mortality and/or heart transplant was performed in 1959 CRT patients implanted in 4 high-volume European centers.

Results: Independent predictors of CRT response in the derivation cohort were: female gender (OR = 2.08, 95% CI 1.26-3.45), NYHA class ≤ III (OR = 2.71, 95% CI 1.63-4.52), left ventricular ejection fraction ≥ 25% (OR = 1.75, 95% CI 1.27-2.41), QRS duration ≥ 150 ms (OR = 1.70, 95% CI 1.25-2.30) and estimated glomerular filtration rate ≥ 60 mL/min (OR = 2.01, 95% CI 1.48-2.72). Each was assigned 1 point. External validation showed good calibration (Hosmer-Lemeshow test-P = 0.95), accuracy (Brier score = 0.19) and discrimination (c-statistic = 0.67), with CRT response increasing progressively from 37.5% in patients with a score of 0 to 91.9% among those with score of 5 (Gamma for trend = 0.44, P < 0.001). Similar results were observed regarding all-cause mortality or heart transplant.

Conclusion: The ScREEN score (Sex category, Renal function, ECG/QRS width, Ejection fraction and NYHA class) is composed of widely validated, easy to obtain predictors of CRT response, and predicts CRT response and overall mortality. It should be helpful in facilitating early consideration of alternative therapies for predicted non-responders to CRT therapy.
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http://dx.doi.org/10.1016/j.ijcard.2018.02.012DOI Listing
June 2018

The subcutaneous implantable cardioverter defibrillator in daily clinical practice.

Swiss Med Wkly 2017 22;147:w14518. Epub 2017 Oct 22.

Department of Cardiology, Electrophysiology and Cardiac Devices, University Heart Centre Zurich, Switzerland.

Introduction: In Switzerland, the first implantation of a subcutaneous implantable cardioverter-defibrillator (S-ICD) took place in November 2012. Up until the end of 2016, a total of 111 S-ICDs have been implanted. The aim of this study was to summarise the experience of a tertiary centre in Switzerland and to discuss the results in the context of international registries.

Methods: All patients in whom an S-ICD was implanted between November 2012 and the end of December 2016 at the University Heart Centre Zurich were included in this study. The clinical records of all patients were reviewed for retrospective collection of baseline characteristics as well as implantation and follow-up data.

Results: A total of 37 S-ICDs were implanted. The majority of patients (81%) were male, the mean age was 47 ± 15 years. The most common underlying cardiac condition was coronary artery disease (30%), followed by hypertrophic cardiomyopathy (24%), inherited channelopathies (19%) and nonischaemic cardiomyopathy (11%). The median left ventricular ejection fraction was 44% (interquartile range 28-61%). There were four peri-interventional complications, all of which were pocket site-related. There were no cases of systemic infection or perioperative death. During a median follow up of 3.7 months, there were three appropriate and successful ICD shocks (8.1%). Two patients (5.4%) experienced a total of three inappropriate shocks, all due to T-wave oversensing.

Conclusion: This first large Swiss experience demonstrates results consistent with available international data. The S-ICD may hence represent an attractive alternative to conventional transvenous ICDs for a variety of patients.
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http://dx.doi.org/10.4414/smw.2017.14518DOI Listing
July 2018

Update Vorhofflimmern 2017.

Praxis (Bern 1994) 2017 Jul;106(14):757-765

1 Elektrophysiologie, Universitäres Herzzentrum Zürich, Zürich.

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http://dx.doi.org/10.1024/1661-8157/a002725DOI Listing
July 2017

Tissue Factor Expression Does Not Predict Mortality in Breast Cancer Patients.

Anticancer Res 2017 06;37(6):3259-3264

Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland

Background: Tissue factor (TF), the trigger of coagulation, not only initiates thrombus formation, but also elicits tumor growth and invasion in breast cancer. However, the characterization of TF expression in breast cancer tissue and its prognostic value remain unclear.

Materials And Methods: Three hundred and three primary breast cancer specimens from the local tumor tissue database were immunostained for TF expression and evaluated semiquantitatively. Tumor characteristics (size, grade, nodal status, and ER expression) as well as patient's survival were assessed.

Results: Expression of TF was detected in 99% of specimens with higher expression in invasive lobular than ductal carcinoma (p=0.008). TF expression correlated with ER expression (p<0.0001) and inversely with tumor grade (p=0.006). Survival analysis did not reveal any prognostic impact of TF expression (p=0.966).

Conclusion: This study - by analyzing TF expression in the largest cohort of breast cancer patients so far - does not support a prognostic impact of TF expression.
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http://dx.doi.org/10.21873/anticanres.11689DOI Listing
June 2017

"Real world" experience in Cardiac Resynchronization Therapy at a Swiss Tertiary Care Center.

Swiss Med Wkly 2017 18;147:w14425. Epub 2017 Apr 18.

University Heart Center Zurich.

Background: Based on a reduction in morbidity and mortality, cardiac resynchronisation therapy (CRT) has evolved as a standard therapy for patients with advanced heart failure.

Objective: To provide insight into patient demographics, safety, echocardiographic remodelling and long-term follow-up of patients treated with CRT in a "real-world" setting at a Swiss tertiary care centre.

Methods: Patients implanted with a CRT device at the University Heart Centre Zurich between 2000 and 2015 were consecutively enrolled. Initial clinical and echocardiographic therapy response as well as long-term follow-up for mortality (defined as all-cause death, heart transplantation or ventricular assist device implantation) and hospitalisation for heart failure were assessed.

Results: A total of 418 patients with a median age of 66 years at the time of CRT implantation (78% male) were enrolled. Serious peri-interventional complications (from the time of implantation up to 14 days thereafter) were rare and included systemic infections in 2.4%, pneumothorax in 3.3% and haematoma requiring revision in 2.2% of cases. Overall, the Kaplan-Meier estimate for 5-year freedom from the composite endpoint (hospitalisation for heart failure or mortality) was 55.8%; the Kaplan-Meier estimate for 5-year freedom from mortality was 64.1%. CRT was associated with a significant symptomatic improvement and left ventricular reverse remodelling. Overall, 3.9% of patients did not respond to cardiac resynchronisation therapy (decline in left ventricular ejection fraction [LVEF] >5%), whereas 35.1% experienced neither a continued decline nor a relevant improvement of LVEF (±5%). In the remaining 61% of patients we observed an improvement in LVEF of more than 5%. Forty percent and 31% of patients were super responders, defined as an absolute LVEF improvement of 10% and by a relative reduction of left ventricular end-diastolic volume index by 20% or more. Super-response to CRT was associated with a significant benefit in terms of survival and rehospitalisation rates.

Conclusion: Our data are consistent with large multicentre trials and indicate that CRT is similarly effective in a real-world setting in Switzerland.
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http://dx.doi.org/10.4414/smw.2017.14425DOI Listing
October 2017

Endothelial LOX-1 activation differentially regulates arterial thrombus formation depending on oxLDL levels: role of the Oct-1/SIRT1 and ERK1/2 pathways.

Cardiovasc Res 2017 Apr;113(5):498-507

Center for Molecular Cardiology, University of Zurich, Winterthurerstr. 190, CH-8057 Zurich, Switzerland.

Aims: The lectin-like oxLDL receptor-1 (LOX-1) promotes endothelial uptake of oxidized low-density lipoprotein (oxLDL) and plays an important role in atherosclerosis and acute coronary syndromes (ACS). However, its role in arterial thrombus formation remains unknown. We investigated whether LOX-1 plays a role in arterial thrombus formation in vivo at different levels of oxLDL using endothelial-specific LOX-1 transgenic mice (LOX-1TG) and a photochemical injury thrombosis model of the carotid artery.

Methods And Results: In mice fed a normal chow diet, time to arterial occlusion was unexpectedly prolonged in LOX-1TG as compared to WT. In line with this, tissue factor (TF) expression and activity in carotid arteries of LOX-1TG mice were reduced by half. This effect was mediated by activation of octamer transcription factor 1 (Oct-1) leading to upregulation of the mammalian deacetylase silent information regulator-two 1 (SIRT1) via binding to its promoter and subsequent inhibition of NF-κB signaling. In contrast, intravenous injection of oxLDL as well as high cholesterol diet for 6 weeks led to a switch from the Oct-1/SIRT1 signal transduction pathway to the ERK1/2 pathway and in turn to an enhanced thrombotic response with shortened occlusion time.

Conclusions: Thus, LOX-1 differentially regulates thrombus formation in vivo depending on the degree of activation by oxLDL. At low oxLDL levels LOX-1 activates the protective Oct-1/SIRT1 pathway, while at higher levels of the lipoprotein switches to the thrombogenic ERK1/2 pathway. These findings may be important for arterial thrombus formation in ACS and suggest that SIRT1 may represent a novel therapeutic target in this context.
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http://dx.doi.org/10.1093/cvr/cvx015DOI Listing
April 2017

Catheter Ablation of Ventricular Tachycardia in Patients With MitraClip Device: Preliminary Findings.

J Cardiovasc Electrophysiol 2017 May 27;28(5):523-530. Epub 2017 Mar 27.

Arrhythmia Unit and Electrophysiology Laboratories, San Raffaele University Hospital, Milan, Italy.

Introduction: Patients with mitral regurgitation are increasingly treated by percutaneous implantation of a MitraClip device (Abbott Park, IL, USA). We investigate the feasibility and safety of the transmitral catheter route for catheter ablation of ventricular tachycardia (VT) in these patients.

Methods: The mitral valve with the MitraClip in situ was crossed under transesophageal 3-dimensional echocardiographic and fluoroscopic guidance using a steerable sheath for ablation of the left ventricle.

Results: Five patients (all males, median age 74.0 ± 16.0 years) who had previously a MitraClip implanted were referred for catheter ablation of VT. The left ventricular ejection fraction was 29.0% ± 24.0%. One patient had both an atrial septal defect and a left atrial appendage occluder device in addition to a MitraClip. The duration between MitraClip implantation and ablation was 1019.0 ± 783.0 days. After transseptal puncture, ablation catheter was successfully steered through the mitral valve with the use of fluoroscopy. A complete high-density map of the substrate in sinus rhythm could be obtained in all patients using multipolar mapping catheters. In 1 patient, mapping was carried out using a mini-basket catheter. Procedural endpoints, noninducibility of all VTs, and abolition of all late potentials were achieved in all patients. Procedure time was 255.0 ± 52.5 minute, fluoroscopy time was 23.0 ± 7.3, and the radiation dose was 61.0 ± 37.5 Gycm . No mitral insufficiency or worsening of regurgitation was documented after the procedure.

Conclusions: This is the first report demonstrating the feasibility and safety of VT ablation in patients with a MitraClip device using the anterograde transmitral catheter route.
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http://dx.doi.org/10.1111/jce.13180DOI Listing
May 2017

Ticagrelor, but not clopidogrel active metabolite, displays antithrombotic properties in the left atrial endocardium.

Eur Heart J 2017 Mar;38(12):916-919

Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.

Aims: Oral anticoagulation is considered standard therapy for stroke prevention in atrial fibrillation (AF). Endocardial activation triggers expression of pro-thrombotic mediators including tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), and contributes to thrombus formation in the left atrial appendage (LAA) of AF patients. Recently, pleiotropic effects of specific P2Y12 receptor antagonists were demonstrated; however, whether these drugs possess antithrombotic effects on LAA endocardial cells currently remains unknown.

Methods And Results: LAA were obtained from 14 patients with known AF undergoing elective cardiac surgery including LAA removal at the University Hospital Zurich. LAA endocardial cells were isolated and pre-incubated with ticagrelor (10-7, 10-6, 10-5M) or clopidogrel active metabolite (CAM) (1.5 × 10-8, 1.5 × 10-7, 1.5 × 10-6 M) before stimulation with tumour necrosis factor-alpha (TNF-α) (10 ng/mL). Finally, TF and PAI-1 expression and activity were analysed. Ticagrelor, unlike CAM, concentration dependently decreased TNF-α-induced TF expression and TF activity in LAA endocardial cells. Further, ticagrelor, but not CAM reduced PAI-1 expression and enzyme activity in TNF-α-stimulated LAA endocardial cells. In contrast, TF pathway inhibitor (TFPI) remained unaffected by both dugs.

Conclusion: Ticagrelor, but not CAM, reduces expression and activity of TF and PAI-1 in LAA endocardial cells isolated from patients with AF, indicating possible local antithrombotic effects. Such pleiotropic properties of ticagrelor may contribute to a reduction in thromboembolic complications in patients with AF.
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http://dx.doi.org/10.1093/eurheartj/ehw578DOI Listing
March 2017

Safety and mid-term outcome of catheter ablation of ventricular tachycardia in octogenarians.

Europace 2017 Aug;19(8):1369-1377

Bristol Heart Institute, Bristol, UK.

Aims: Radiofrequency (RF) catheter ablation (CA) is superior to standard medical therapy in controlling recurrent ventricular tachycardia (VT). The majority of procedures have been performed in a middle-aged population. The outcome of VT ablation in the elderly has not been described.

Methods And Results: We retrospectively studied the outcome and safety of CA of VT in octogenarians performed in four European centres. The population consisted of patients presenting with recurrent VT refractory to medical therapy. Patients aged over 80 years were compared with younger patients undergoing CA. Clinical characteristics, procedural data, complications, and outcomes were examined. Implantable cardioverter-defibrillator (ICD) therapy data were collected. A total of 54 consecutive octogenarian patients underwent RF CA of VT and represented the study group (42 males, age 82.8 ± 2.7 years) compared with a control group of 104 younger patients (85 males, age 66.7 ± 8.9 years). Mean follow-up was 33 ± 48 months. Implantable cardioverter-defibrillators were present in 81 and 86% of patients, respectively (P = 0.93). Left ventricular ejection fraction was 29% ± 8.2 in octogenarians vs. 34% ± 10.2 in the younger group (P < 0.01). More major complications occurred in octogenarians (18 vs. 2%, P < 0.01). During follow-up, there were more ICD shocks in the octogenarians (28 vs. 15%, P < 0.01). The Kaplan-Meier curve of survival after VT ablation confirms comparable survival rates at 1 year, but the elderly have poor survival in the mid-term. Survival in the elderly post VT ablation is comparable with that in an age-matched cohort with ICDs but no VT storm.

Conclusion: Octogenarians undergoing CA of VT have more risk factors, higher risk of complications and ICD shocks, but demonstrate comparable short-term survival rates.
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http://dx.doi.org/10.1093/europace/euw236DOI Listing
August 2017

The MAP kinase JNK2 mediates cigarette smoke-induced arterial thrombosis.

Thromb Haemost 2017 01 20;117(1):83-89. Epub 2016 Oct 20.

Dr. Giovanni G. Camici, PhD, Center for Molecular Cardiology, Wagistrasse 12, 8952 Schlieren, Switzerland, Tel.: +41 44 635 64 68, Fax: +41 44 635 68 27, E-mail:

Despite public awareness of its deleterious effects, smoking remains a major cause of death. Indeed, it is a risk factor for atherothrombotic complications and in line with this, the introduction of smoking ban in public areas reduced smoking-associated cardiovascular complications. Nonetheless, smoking remains a major concern, and molecular mechanisms by which it causes cardiovascular disease are not known. Peripheral blood monocytes from healthy smokers displayed increased JNK2 and tissue factor (TF) gene expression compared to non-smokers (n=15, p<0.05). Similarly, human aortic endothelial cells exposed to cigarette smoke total particulate matter (CS-TPM) revealed increased TF expression mediated by JNK2 (n=4; p<0.05). Wild-type and JNK2 mice were exposed to cigarette smoke for two weeks after which arterial thrombosis was investigated. Wild-type mice exposed to smoke displayed reduced time to thrombotic arterial occlusion (n=8; p<0.05) and increased tissue factor activity (n=7; p<0.05) as compared to wild-type controls (n=6), while JNK2mice exposed to smoke maintained an unaltered thrombotic potential (n=8; p=NS) and tissue factor activity (n=8) comparable to that of JNK2 and wild-type controls (n=6; p=NS). Smoking caused an increased production of reactive oxygen species (ROS) in wild-type but not in JNK2 mice (n=7; p<0.05 for wild-type mice and n=5-6; p=NS for JNK2 mice). In conclusion, the MAP kinase JNK2 mediates cigarette smoke-induced TF activation, arterial thrombosis and ROS production. These results underscore a major role of JNK2 in smoke-mediated thrombus formation and may offer an attractive target to prevent smoke-related thrombosis in those subjects which do not manage quitting.
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http://dx.doi.org/10.1160/TH16-05-0351DOI Listing
January 2017

Efficacy and Safety of Long-Term Imatinib Therapy for Pulmonary Arterial Hypertension.

Respiration 2015 3;89(6):515-24. Epub 2015 Jun 3.

Pulmonary Hypertension Program, Clinic of Pneumology, University Hospital Zurich, Zurich, Switzerland.

Background: Antiproliferative strategies have emerged as a potential therapeutic option for pulmonary arterial hypertension (PAH).

Objective: To evaluate the long-term efficacy and safety of imatinib.

Methods: This is an observational study of 15 patients with idiopathic PAH (n = 13) or PAH associated with connective tissue disease (n = 2) treated off-label with imatinib 400 mg daily. Pulmonary hypertension-specific therapy was established in all patients (triple therapy in 10, dual therapy in 3, and monotherapy in 2 patients).

Results: After 6 months, improvement in hemodynamics (p < 0.01), functional class (p = 0.035), and quality of life (p = 0.005) was observed. After a median follow-up of 37 months, there was a sustained improvement in functional class (p = 0.032), quality of life (p = 0.019), and echocardiographic parameters of right ventricular function (p < 0.05). Three patients (20%) presented with completely normal echocardiography, absent tricuspid regurgitation, and normal pro-brain natriuretic peptide levels, indicative of 'hemodynamic remission'. Of note, however, only 1 case was assessed by invasive hemodynamics. The overall 1- and 3-year survival was 100 and 90%, respectively. Two patients experienced a subdural hematoma (SDH), which in both cases resolved without sequelae. After careful consultation of the potential risks and benefits, all patients as well as a safety cohort of 9 subsequent cases decided to continue the imatinib therapy. After adjusting the target international normalized ratio (INR) to around 2.0, no further cases of SDH occurred during 50 patient-years.

Conclusions: Long-term treatment with imatinib may improve the functional class and quality of life. Single cases might even attain hemodynamic remission. The occurrence of 5% SDH per patient-years is concerning. However, adjusting the INR to around 2.0 might obviate this complication.
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http://dx.doi.org/10.1159/000381923DOI Listing
March 2016

Novel use of the midas rex neurosurgical drill to release silicone glue entrapped pacing leads.

Indian Pacing Electrophysiol J 2015 Jan-Feb;15(1):65-7. Epub 2015 Apr 1.

Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380697PMC
http://dx.doi.org/10.1016/s0972-6292(16)30844-0DOI Listing
April 2015

Increased prothrombotic profile in the left atrial appendage of atrial fibrillation patients.

Int J Cardiol 2015 Apr 11;185:250-5. Epub 2015 Mar 11.

Cardiology, University Heart Center, University Hospital Zurich, Switzerland; Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Center for Integrative Human Physiology (ZHIP), University of Zurich, Switzerland. Electronic address:

Background: Atrial fibrillation (AF) is associated with an increased risk for thromboembolic events. While observational data demonstrated that the majority of clots are formed within the left atrial appendage, the mechanisms behind this finding remain unclear also due to the fact that vitro studies so far have been hampered by the inability to isolate and culture cells from the atrial appendages.

Methods: Patients suffering from AF undergoing cardiac surgery were recruited for this study and endocardial cells from their left (LAA) and right atrial appendage (RAA) were isolated and cultured according to a novel established protocol. Once in culture, cells were stimulated with TNF-α (10 ng/mL) and the expression of prothrombotic as well as proinflammatory markers was analyzed.

Results: FACS analysis confirmed a high purity (98%) of isolated LAA endocardial cells. TNF-α significantly increased tissue factor (TF) and PAI-1 expression (n=5; P<0.005), while TFPI remained unchanged. Similarly, expression of VCAM-1 was significantly higher in the LAA as compared to the RAA (n=5; P<0.0001).

Conclusion: According to our newly established cell isolation protocol, this study reveals that in patients with AF, the endocardium of the LAA displays an increased prothrombotic and proinflammatory profile as compared to the RAA. This novel observation may constitute an important mechanism to explain the increased propensity of the LAA for clot formation, as well as the predominance of LAA-related thromboembolic complications in AF patients, and may have important implications for the development of novel treatment strategies.
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http://dx.doi.org/10.1016/j.ijcard.2015.03.092DOI Listing
April 2015

Haemosiderin-laden sputum macrophages for diagnosis in pulmonary veno-occlusive disease.

PLoS One 2014 12;9(12):e115219. Epub 2014 Dec 12.

Zurich Pulmonary Hypertension Program, Clinic for Internal Medicine, University Hospital Zurich, Zurich, Switzerland; Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland; Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom.

Aims: Pulmonary veno-occlusive disease (PVOD) is a rare condition of pulmonary arterial hypertension (PAH), in which post-capillary veins are affected. Since the therapeutic approach in PVOD differs from other forms of PAH, it is crucial to establish the diagnosis. Due to the fact that affected patients are often hemodynamically unstable, minimal invasive procedures are necessary for the diagnostic work-up. Chronic alveolar haemorrhage has been observed during bronchoalveolar lavage in PVOD cases. This study therefore investigates whether signs of alveolar haemorrhage can also be found in the sputum of these patients.

Methods And Results: Six patients suffering from PVOD were included in this analysis. As controls, patients with idiopathic PAH (n = 11), chronic thromboembolic PH (n = 9) and with sclerodermia-associated PH (n = 10) were assessed. Sputum from every patient was obtained by a non-invasive manner. The amount of haemosiderin-laden macrophages was determined using the Golde score. There were statistically significant more haemosiderin-laden macrophages in the sputum of patients suffering from PVOD as compared to the other groups (P<0.05). Assuming a cut-off of 200 on the Golde score, all of the 6 PVOD patients surpassed this value compared with only 1 out of the 30 cases with precapillary PH. Thus, sensitivity and specificity with respect to the diagnosis of PVOD was 100% and 97%, respectively.

Conclusion: The content of haemosiderin-laden macrophages in the sputum of patients suffering from PVOD is significantly higher as compared to other forms of PH and may be useful in the non-invasive diagnostic work-up of these patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115219PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264865PMC
March 2016

Suitability, efficacy, and safety of vernakalant for new onset atrial fibrillation in critically ill patients.

Crit Care Res Pract 2014 12;2014:826286. Epub 2014 May 12.

Cardiosurgical Intensive Care Unit, Institute of Anesthesiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

Objectives. This study investigates the suitability, safety, and efficacy of vernakalant in critically ill patients with new onset atrial fibrillation (AF) after cardiac surgery. Methods. Patients were screened for inclusion and exclusion criteria according to the manufacturers' recommendations. Included patients were treated with 3 mg/kg of vernakalant over 10 min and, if unsuccessful, a second dose of 2 mg/kg. Blood pressure was measured continuously for 2 hours after treatment. Results. Of the 191 patients screened, 159 (83%) were excluded, most importantly due to hemodynamic instability (59%). Vernakalant was administered to 32 (17% of the screened) patients. Within 6 hours, 17 (53%) patients converted to sinus rhythm. Blood pressure did not decrease significantly 10, 30, 60, and 120 minutes after the vernakalant infusion. However, 11 patients (34%) experienced a transient decrease in mean arterial blood pressure <60 mmHg. Other adverse events included nausea (n = 1) and bradycardia (n = 2). Conclusions. Applying the strict inclusion and exclusion criteria provided by the manufacturer, only a minority of postoperative ICU patients with new onset AF qualified for vernakalant. Half of the treated patients converted to sinus rhythm. The drug was well tolerated, but close heart rate and blood pressure monitoring remains recommended.
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http://dx.doi.org/10.1155/2014/826286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036718PMC
June 2014

Endothelial overexpression of LOX-1 increases plaque formation and promotes atherosclerosis in vivo.

Eur Heart J 2014 Oct 12;35(40):2839-48. Epub 2014 Jan 12.

Cardiovascular Research, Institute of Physiology, University of Zurich; and Cardiovascular Center, Cardiology, University Hospital Zurich, 8091 Zurich, Switzerland Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland

Aims: Lectin-like oxLDL receptor-1 (LOX-1) mediates the uptake of oxidized low-density lipoprotein (oxLDL) in endothelial cells and macrophages. However, the different atherogenic potential of LOX-1-mediated endothelial and macrophage oxLDL uptake remains unclear. The present study was designed to investigate the in vivo role of endothelial LOX-1 in atherogenesis.

Methods And Results: Endothelial-specific LOX-1 transgenic mice were generated using the Tie2 promoter (LOX-1TG). Oxidized low-density lipoprotein uptake was enhanced in cultured endothelial cells, but not in macrophages of LOX-1TG mice. Six-week-old male LOX-1TG and wild-type (WT) mice were fed a high-cholesterol diet (HCD) for 30 weeks. Increased reactive oxygen species production, impaired endothelial nitric oxide synthase activity and endothelial dysfunction were observed in LOX-1TG mice as compared with WT littermates. LOX-1 overexpression led to p38 phosphorylation, increased nuclear factor κB activity and subsequent up-regulation of vascular cell adhesion molecule-1, thereby favouring macrophage accumulation and aortic fatty streaks. Consistently, HCD-fed double-mutant LOX-1TG/ApoE(-/-) displayed oxidative stress and vascular inflammation with higher aortic plaques than ApoE(-/-) controls. Finally, bone marrow transplantation experiments showed that endothelial LOX-1 was sufficient for atherosclerosis development in vivo.

Conclusions: Endothelial-specific LOX-1 overexpression enhanced aortic oxLDL levels, thereby favouring endothelial dysfunction, vascular inflammation and plaque formation. Thus, LOX-1 may serve as a novel therapeutic target for atherosclerosis.
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http://dx.doi.org/10.1093/eurheartj/eht532DOI Listing
October 2014