Publications by authors named "Georg Nickenig"

509 Publications

Fate of Tricuspid Regurgitation in Patients Undergoing Transcatheter Edge-to-Edge Mitral Valve Repair.

EuroIntervention 2021 Mar 2. Epub 2021 Mar 2.

Department of Internal Medicine II, University Hospital Bonn, Bonn, Germany.

Background: Mitral valve repair may lead to alterations of tricuspid regurgitation (TR).

Aims: We investigated alterations, predictors and prognostic relevance of TR evolution in a large-scale multicentre population of patients undergoing transcatheter mitral valve repair (TMVR) via MitraClip.

Methods: In total, we included 531 TMVR-patients with at least one available follow-up echocardiography. TR-improvement was defined as a TR ≥II at baseline, which showed a decline of at least one TR-categorization.

Results: Distribution of pre-procedural TR severity was TR0/I 41% (220/531), TRII 39% (209/531) and TR≥III 19% (102/531), respectively. Follow-up echocardiography was at 308±187days. TR severity improved to TR0/I 49% (259/531), TRII 35% (183/531) and TRIII 17% (89/531), p=0.003. Out of 311 patients with TR≥II at baseline, 41% (127/311) showed TR-improvement. Atrial fibrillation (AF), residual mitral regurgitation ≥II (rMR) and tricuspid annular diameter (TAD) remained variables which prevented TR-improvement [odds ratio 0.49(0.29-0.84), 0.47(0.27-0.81) & 0.97(0.93-0.997), respectively]. TR-improvement was associated with better event-free survival regarding post-procedural heart-failure hospitalization (HHF) [hazard ratio 0.6(0.38-0.94)]. The main changes of TR-severity occurred within 3-month post TMVR (p=0.006), while there were only minor TR-changes between 3 and 12-month of follow-up (p=0.813).

Conclusions: TR-improvement was frequent after TMVR. Predictors preventing TR-improvement were AF, post-procedural rMR, and TAD. Furthermore, TR-improvement was an early phenomenon primarily occurring within the first three months post TMVR and served as a suitable marker of reduced HHF.
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http://dx.doi.org/10.4244/EIJ-D-20-01094DOI Listing
March 2021

Long-term clinical outcome and mortality risks after paclitaxel-coated balloon angioplasty in patients with peripheral artery disease: An observational clinical study.

Health Sci Rep 2021 Mar 26;4(1):e236. Epub 2021 Jan 26.

Department of Internal Medicine II-Cardiology, Pulmonology and Angiology University Hospital Bonn Bonn Germany.

Background And Aims: Drug-eluting devices (DEDs) are usually used as a standard therapy for revascularization in femoropopliteal artery disease. Randomized controlled trails have found that DEDs with paclitaxel result in superior patency rates and decreased target lesion revascularization. A meta-analysis by Katsanos et al indicated an increased long-term mortality in patients treated with paclitaxel-coated devices. The aim of this observational clinical study was to assess the long-term clinical outcomes and mortality risk after paclitaxel-coated balloon angioplasty in patients with symptomatic peripheral artery disease.

Methods: We retrospectively evaluated 287 patients with peripheral interventions, including 173 drug-coated balloon (DCB) angioplasties and 114 plain old balloon angioplasties (POBA), performed at our center between 2015 and 2018.

Results: There were no significant differences in mortality rates between patients who received DCB angioplasty and those who received POBA. In the first year, the hazard ratio (HR) for DCB angioplasty was 0.59 (95% confidence interval [CI] 0.31 to 1.12, = .104). After 2 years, this HR was 0.64 (95% CI 0.36-1.17, = .145), while the 3-year and 4-year HR increased to 0.71 and 1.30 (3-year: 95% CI 0.37-1.33, = ,283; 4-year: 95% CI 0.55-3.08, = .546). No paclitaxel dose-response relationship with mortality rate was identified when adjusted for key predictors of mortality.

Conclusions: Analyses of patient level data identified no significant mortality differences between DCB angioplasty and POBA after 4 years of follow-up. Furthermore, there was no dose-response relationship between paclitaxel and mortality. These findings demonstrate that paclitaxel DCB is safe. Further long-term multicenter studies are needed to determine the risk of late mortality.
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http://dx.doi.org/10.1002/hsr2.236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837675PMC
March 2021

QRS duration is a risk indicator of adverse outcomes after MitraClip.

Catheter Cardiovasc Interv 2021 Feb 1. Epub 2021 Feb 1.

Heart Center Bonn, Department of Medicine II, University Hospital Bonn, Bonn, Germany.

Background: While QRS duration is a known marker of left ventricular (LV) function, little is known about its utility for predicting clinical prognosis after transcatheter mitral valve repair (TMVR). We investigated the association between QRS duration and one-year adverse events after TMVR with the MitraClip system.

Methods: From January 2011 through April 2019, we identified consecutive patients who underwent TMVR. Patients who had prior cardiac resynchronization therapy or a ventricular pacing rhythm were excluded. The patients were divided into two groups according to their QRS duration (<120 or ≥ 120 ms). Cox proportional hazard model was applied to determine the association between QRS duration and the composite outcome (all-cause mortality and re-hospitalization due to heart failure) within 1 year.

Results: A total of 348 patients were analyzed. Prolonged QRS duration (≥120 ms) was associated with an increased risk of the composite outcome (adjusted-HR 2.35, 95%CI 1.30-4.24, p = .005). There was a linear relationship between prolonged QRS duration and the increased risk of the composite outcomes. The observed association was consistent both in patients with left ventricular ejection fraction ≤35% and those with >35%. Furthermore, a QRS duration ≥120 ms was associated with lower improvement of LVEF at follow-up (adjusted-β coefficient - 5.31%, 95%CI -8.17 to -2.46, p < .001).

Conclusions: Prolonged QRS duration was associated with an increased risk of mortality and re-hospitalization and less improvement of LVEF following TMVR. QRS duration could be a useful marker to predict adverse outcomes and LV function after TMVR.
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http://dx.doi.org/10.1002/ccd.29505DOI Listing
February 2021

"Get with the Guidelines Heart Failure Risk Score" for mortality prediction in patients undergoing MitraClip.

Clin Res Cardiol 2021 Jan 31. Epub 2021 Jan 31.

Department of Cardiology, Angiology, Pneumology and Medical Intensive Care, Heart Center of the University of Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany.

Background: Reliable risk scores in patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) are lacking. Heart failure is common in these patients, and risk scores derived from heart failure populations might help stratify TMVR patients.

Methods: Consecutive patients from three Heart Centers undergoing TMVR were enrolled to investigate the association of the "Get with the Guidelines Heart Failure Risk Score" (comprising the variables systolic blood pressure, urea nitrogen, blood sodium, age, heart rate, race, history of chronic obstructive lung disease) with all-cause mortality.

Results: Among 815 patients with available data 177 patients died during a median follow-up time of 365 days. Estimated 1-year mortality by quartiles of the score (0-37; 38-42, 43-46 and more than 46 points) was 6%, 10%, 23% and 30%, respectively (p < 0.001), with good concordance between observed and predicted mortality rates (goodness of fit test p = 0.46). Every increase of one score point was associated with a 9% increase in the hazard of mortality (95% CI 1.06-1.11%, p < 0.001). The score was associated with long-term mortality independently of left ventricular ejection fraction, NYHA class and NTproBNP, and was equally predictive in primary and secondary mitral regurgitation.

Conclusion: The "Get with the Guidelines Heart Failure Risk Score" showed a strong association with mortality in patients undergoing TMVR with additive information beyond traditional risk factors. Given the routinely available variables included in this score, application is easy and broadly possible.
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http://dx.doi.org/10.1007/s00392-021-01804-3DOI Listing
January 2021

Reply to "The endocannabinoid 2-arachidonoylglycerol inhibits endothelial function and repair through cannabinoid 1 (CB1) receptor".

Int J Cardiol 2021 Jan 28. Epub 2021 Jan 28.

Department of Internal Medicine II Cardiology, Pneumology, Angiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.

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http://dx.doi.org/10.1016/j.ijcard.2021.01.033DOI Listing
January 2021

Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches.

J Mol Med (Berl) 2021 Mar 22;99(3):335-348. Epub 2021 Jan 22.

Heart Center, Department of Medicine II, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD). Both conditions are rising in incidence as well as prevalence, creating poor outcomes for patients and high healthcare costs. Recent data suggests CKD to be an independent risk factor for CVD. Accumulation of uremic toxins, chronic inflammation, and oxidative stress have been identified to act as CKD-specific alterations that increase cardiovascular risk. The association between CKD and cardiovascular mortality is markedly influenced through vascular alterations, in particular atherosclerosis and vascular calcification (VC). While numerous risk factors promote atherosclerosis by inducing endothelial dysfunction and its progress to vascular structural damage, CKD affects the medial layer of blood vessels primarily through VC. Ongoing research has identified VC to be a multifactorial, cell-mediated process in which numerous abnormalities like mineral dysregulation and especially hyperphosphatemia induce a phenotype switch of vascular smooth muscle cells to osteoblast-like cells. A combination of pro-calcifying stimuli and an impairment of inhibiting mechanisms like fetuin A and vitamin K-dependent proteins like matrix Gla protein and Gla-rich protein leads to mineralization of the extracellular matrix. In view of recent studies, intercellular communication pathways via extracellular vesicles and microRNAs represent key mechanisms in VC and thereby a promising field to a deeper understanding of the involved pathomechanisms. In this review, we provide an overview about pathophysiological mechanisms connecting CKD and CVD. Special emphasis is laid on vascular alterations and more recently discovered molecular pathways which present possible new therapeutic targets.
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http://dx.doi.org/10.1007/s00109-021-02037-7DOI Listing
March 2021

Transcatheter Edge-to-Edge Repair for Treatment of Tricuspid Regurgitation.

J Am Coll Cardiol 2021 Jan;77(3):229-239

Heart Center University Hospital, Bonn, Germany.

Background: Tricuspid regurgitation (TR) is a frequent disease with a progressive increase in mortality as disease severity increases. Transcatheter therapies for treatment of TR may offer a safe and effective alternative to surgery in this high-risk population.

Objectives: The purpose of this report was to study the 1-year outcomes with the TriClip transcatheter tricuspid valve repair system, including repair durability, clinical benefit and safety.

Methods: The TRILUMINATE trial (n = 85) is an international, prospective, single arm, multicenter study investigating safety and performance of the TriClip Tricuspid Valve Repair System in patients with moderate or greater TR. Echocardiographic assessment was performed by a core laboratory.

Results: At 1 year, TR was reduced to moderate or less in 71% of subjects compared with 8% at baseline (p < 0.0001). Patients experienced significant clinical improvements in New York Heart Association (NYHA) functional class I/II (31% to 83%, p < 0.0001), 6-minute walk test (272.3 ± 15.6 to 303.2 ± 15.6 meters, p = 0.0023) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score (improvement of 20 ± 2.61 points, p < 0.0001). Significant reverse right ventricular remodeling was observed in terms of size and function. The overall major adverse event rate and all-cause mortality were both 7.1% at 1 year.

Conclusion: Transcatheter tricuspid valve repair using the TriClip device was found to be safe and effective in patients with moderate or greater TR. The repair itself was durable at reducing TR at 1 year and was associated with a sustained and marked clinical benefit with low mortality after 1 year in a fragile population that was at high surgical risk. (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR; NCT03227757).
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http://dx.doi.org/10.1016/j.jacc.2020.11.038DOI Listing
January 2021

Transcatheter Aortic Valve Replacement With the LOTUS Edge System: Early European Experience.

JACC Cardiovasc Interv 2021 Jan 25;14(2):172-181. Epub 2020 Nov 25.

Department of Cardiology, Galway University Hospital, Galway, Ireland; National University of Ireland Galway, Galway, Ireland. Electronic address:

Objectives: The aim of this study was to evaluate the short-term safety and efficacy of transcatheter aortic valve replacement (TAVR) with the LOTUS Edge system.

Background: The LOTUS Edge system was commercially re-released in April 2019. The authors report the first European experience with this device.

Methods: A multicenter, single-arm, retrospective registry was initiated to evaluate short-term clinical outcomes. Included cases are the first experience with this device and new implantation technique in Europe. Clinical, echocardiographic, and computed tomographic data were analyzed. Endpoints were defined according to Valve Academic Research Consortium-2 and were site reported.

Results: Between April and November 2019, 286 consecutive patients undergoing TAVR with the LOTUS Edge system at 18 European centers were included. The mean age and Society of Thoracic Surgeons score were 81.2 ± 6.9 years and 5.2 ± 5.4%, respectively. Nearly one-half of all patients (47.9%) were considered to have complex anatomy. Thirty-day major adverse events included death (2.4% [n = 7]) and stroke (3.5% [n = 10]). After TAVR, the mean aortic valve area was 1.9 ± 0.9 cm, and the mean transvalvular gradient was 11.9 ± 5.7 mm Hg. None or trace paravalvular leak (PVL) occurred in 84.4% and moderate PVL in 2.0%. There were no cases of severe PVL. New permanent pacemaker (PPM) implantation was required in 25.9% among all patients and 30.8% among PPM-naive patients.

Conclusions: Early experience with the LOTUS Edge system demonstrated satisfactory short-term safety and efficacy, favorable hemodynamic data, and very low rates of PVL in an anatomically complex cohort. New PPM implantation remained high. Further study will evaluate if increasing operator experience with the device and new implantation technique can reduce the incidence of PPM implantation.
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http://dx.doi.org/10.1016/j.jcin.2020.09.044DOI Listing
January 2021

Moving (re-shaping) the mitral annulus.

EuroIntervention 2021 Jan;16(13):1044-1045

University Hospital Bonn, Bonn, Germany.

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http://dx.doi.org/10.4244/EIJV16I13A190DOI Listing
January 2021

The effect of transcatheter aortic valve implantation approaches on mortality.

Catheter Cardiovasc Interv 2021 Jan 14. Epub 2021 Jan 14.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.

Objectives: We aimed to evaluate the effect of transcatheter aortic valve implantation (TAVI) approaches on mortality and identify effect modifiers and predictors for mortality.

Background: Alternative access routes to transfemoral (TF) TAVI include the surgical intra-thoracic direct-aortic (DA) and transapical (TA) approach. TA TAVI has been associated with a higher mortality rate. We hypothesized that this is related to effect modifiers, in particular the left ventricular ejection fraction (LVEF).

Methods: This multicentre study derived its data from prospective registries. To adjust for confounders, we used propensity-score based, stabilized inverse probability weighted Cox regression models.

Results: In total, 5,910 patients underwent TAVI via TF (N = 4,072), DA (N = 524), and TA (N = 1,314) access. Compared to TF, 30-day mortality was increased among DA (HR 1.87, 95%CI 1.26-2.78, p = .002) and TA (HR 3.34, 95%CI 2.28-4.89, p < .001) cases. Compared to TF, 5-year mortality was increased among TA cases (HR 1.50, 95%CI 1.24-1.83, p < .001). None of the variables showed a significant interaction between the approaches and mortality. An impaired LVEF (≤35%) increased mortality in all approaches.

Conclusions: The surgical intra-thoracic TA and DA TAVI are both associated with a higher 30-day mortality than TF TAVI. TA TAVI is associated with a higher 5-year mortality than TF TAVI. The DA approach may therefore have some advantages over the TA approach when TF access is not feasible.
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http://dx.doi.org/10.1002/ccd.29456DOI Listing
January 2021

Incidence, predictors and outcomes of device-related thrombus after left atrial appendage closure with the WATCHMAN device-Insights from the EWOLUTION real world registry.

Catheter Cardiovasc Interv 2021 Jan 8. Epub 2021 Jan 8.

Cardiology Department, St Antonius Hospital, Nieuwegein, the Netherlands.

Background: In this analysis of the EWOLUTION registry, we evaluated the incidence, relevance and predictors of device-related thrombus in a large multi-center real-world cohort undergoing LAAc with the WATCHMAN device.

Methods And Results: We analyzed the 835 patients who underwent percutaneous LAA closure with the WATCHMAN device in the EWOLUTION registry in whom at least one TEE follow up was performed. Patients were 74 ± 9 y/o and were at high risk for stroke and bleeding (CHA2DS2-VASC-Score 4.3 ± 1.7; HAS-BLED-Score 2.3 ± 1.2). Device-related thrombus was detected in 4.1% (34/835) after a median of 54 days (IQR 42-111 days) with 91.2% (31/34) being detected within 3 months after the procedure or at the time of first TEE. Hereby DRT occurred irrespective of postprocedural anticoagulation. Patients with DRT more frequently had long-standing, non-paroxysmal atrial fibrillation (82.4 vs. 64.9%, p < .01), evidence of dense spontaneous echo contrast (26.5 vs. 11.9%, p = .03) and larger LAA diameters at the ostium (22.8 ± 3.5 vs. 21.1 ± 3.5 mm, p < .01) compared to patients without DRT. Left ventricular ejection fraction, device compression ratio and the incidence of renal dysfunction did not differ between the two groups. In a multivariate analysis, only non-paroxysmal atrial fibrillation identified as an independent predictor of developing DRT. Specific treatment of DRT was initiated in 62% (21/34) of patients whereas resolution was confirmed in 86% (18/21) of cases. Overall, no significant differences in annual rates of stroke/TIA or systemic embolism were observed in patients with or without DRT (DRT 1.7 vs. No-DRT 2.2%/year, p = .8).

Conclusions: In real-world patients undergoing LAAc with the WATCHMAN device, DRT is rare. DRT was most frequently detected within the first 3 months after LAAc regardless of post-procedural regimen and was not associated with an increased risk of stroke or SE. While long-standing atrial fibrillation was the only independent factor associated with DRT, medical treatment of DRT resulted in a resolution of thrombi in most cases.
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http://dx.doi.org/10.1002/ccd.29458DOI Listing
January 2021

Predictors of high residual gradient after transcatheter aortic valve replacement in bicuspid aortic valve stenosis.

Clin Res Cardiol 2021 Jan 3. Epub 2021 Jan 3.

Interventional Cardiology Unit, GVM Care and Research, Maria Cecilia Hospital, via della Corriera 1, 48033, Cotignola, Ravenna, Italy.

Objectives: To define the incidence of high residual gradient (HRG) after transcatheter aortic valve replacement (TAVR) in BAVs and their impact on short term outcome and 1-year mortality.

Background: Transcatheter heart valves (THVs) offer good performance in tricuspid aortic valves with low rate of HRG. However, data regarding their performance in bicuspid aortic valves (BAV) are still lacking.

Methods: The BEAT (Balloon vs Self-Expandable valve for the treatment of bicuspid Aortic valve sTenosis) registry included 353 consecutive patients who underwent TAVR (Evolut R/PRO or Sapien 3 valves) in BAV between June 2013 and October 2018. The primary endpoint was device unsuccess with post-procedural HRG (mean gradient ≥ 20 mmHg). The secondary endpoint was to identify the predictors of HRG following the procedure.

Results: Twenty patients (5.6%) showed HRG after TAVR. Patients with HRG presented higher body mass index (BMI) (30.7 ± 9.3 vs. 25.9 ± 4.8; p < 0.0001) and higher baseline aortic mean gradients (57.6 ± 13.4 mmHg vs. 47.7 ± 16.6, p = 0.013) and more often presented with BAV of Sievers type 0 than patients without HRG. At multivariate analysis, BMI [odds ratio (OR) 1.12; 95% confidence interval (CI) 1.05-1.20, p = 0.001] and BAV type 0 (OR 11.31, 95% CI 3.45-37.06, p < 0.0001) were confirmed as independent predictors of high gradient.

Conclusion: HRG following TAVR in BAVs is not negligible and is higher among patients with high BMI and with BAV 0 anatomy.
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http://dx.doi.org/10.1007/s00392-020-01793-9DOI Listing
January 2021

PASCAL versus MitraClip-XTR edge-to-edge device for the treatment of tricuspid regurgitation: a propensity-matched analysis.

Clin Res Cardiol 2021 Mar 12;110(3):451-459. Epub 2020 Dec 12.

Herzzentrum Bonn, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: Transcatheter tricuspid valve repair (TTVR) is a promising technique for the treatment of tricuspid regurgitation (TR). Data comparing the performance of novel edge-to-edge devices (PASCAL and MitraClip-XTR) are scarce.

Methods: We identified 80 consecutive patients who underwent TTVR using either the PASCAL or MitraClip-XTR system to treat symptomatic TR from July 2018 to June 2020. To adjust for baseline imbalances, we performed a propensity score (PS) 1:1 matching. The primary endpoint was a reduction in TR severity by at least one grade at 30 days.

Results: The PS-matched cohort (n = 44) was at high-surgical risk (EuroSCORE II: 7.5% [interquartile range (IQR) 4.8-12.1%]) with a mean TR grade of 4.3 ± 0.8 and median coaptation gap of 6.2 mm [IQR 3.2-9.1 mm]. The primary endpoint was similarly observed in both groups (PASCAL: 91% vs. MitraClip-XTR: 96%). Multiple device implantation was the most common form (59% vs. 82%, p = 0.19), and the occurrence of SLDA was comparable between the PASCAL and MitraClip-XTR system (5.7% [2 of 35 implanted devices] vs. 4.4% [2 of 45 implanted devices], p = 0.99). No periprocedural death or conversions to surgery occurred, and 30-day mortality (5.0% vs. 5.0%, log-rank p = 0.99) and 3-month mortality (10.0% vs. 5.0%, log-rank p = 0.56) were similar between both groups. During follow-up, functional NYHA class, 6-min walking distance, and health status improved in both groups.

Conclusions: Both TTVR devices, PASCAL and MitraClip-XTR, appeared feasible and comparable for an effective TR reduction. Randomized head-to-head comparisons will help to further define the appropriate scope of application of each system.
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http://dx.doi.org/10.1007/s00392-020-01784-wDOI Listing
March 2021

COPD Does Not Corrupt COAPT.

JACC Cardiovasc Interv 2020 Dec;13(23):2804-2805

Heart Center of the University Hospital Bonn, Bonn, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jcin.2020.10.023DOI Listing
December 2020

German Multicenter Experience With a New Leaflet-Based Transcatheter Mitral Valve Repair System for Mitral Regurgitation.

JACC Cardiovasc Interv 2020 Dec;13(23):2769-2778

Department of Cardiology, Heart Centre, Faculty of Medicine, University of Cologne, Cologne, Germany. Electronic address:

Objectives: The aim of this study was to investigate the procedural and short-term safety and efficacy of a new leaflet-based transcatheter mitral valve repair system.

Background: The PASCAL repair system has been recently approved for percutaneous treatment of mitral regurgitation (MR). Novel characteristics are broad paddles positioned around a central spacer and the ability for independent leaflet capture.

Methods: Procedural and 30-day outcomes were investigated in the first 309 patients with symptomatic MR 3+/4+ treated with the PASCAL repair system at 10 sites. Primary efficacy endpoints were technical success and degree of residual MR at discharge. The primary safety endpoint was the rate of major adverse events (MAE).

Results: Among the 309 patients (mean age 77 ± 10 years, 42% women, mean European System for Cardiac Operative Risk Evaluation II score 5.8 ± 4.5%) included in this study, MR etiology was degenerative in 33%, functional in 52%, and mixed in 16%. Eighty-six percent of patients were in New York Heart Association functional class III or IV. The technical success rate was 96%. Of 308 patients discharged alive, MR was ≤2+ in 93.5%. At 30 days, the MAE rate was 4.1%, with an estimated all-cause mortality rate of 2.0%, and 72% of patients were in New York Heart Association functional class ≤II (p < 0.001). Rates of device success and CLASP (Edwards PASCAL Transcatheter Mitral Valve Repair System Study) trial-defined clinical success were 81.9% and 86.9%, respectively. Single-leaflet device attachment occurred in 7 patients (2.3%).

Conclusions: Mitral valve repair with the PASCAL system in the early post-approval phase was effective and safe, with high procedural success rates and low rates of MAE. MR was significantly reduced, accompanied by significant improvement in functional status.
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http://dx.doi.org/10.1016/j.jcin.2020.08.025DOI Listing
December 2020

AIM2 Stimulation Impairs Reendothelialization and Promotes the Development of Atherosclerosis in Mice.

Front Cardiovasc Med 2020 11;7:582482. Epub 2020 Nov 11.

Department of Internal Medicine II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany.

Atherosclerosis has been shown to result from chronic inflammation caused by constitutive activation of the pattern recognition receptors (PRR), which are principle effectors of the innate immune system. PRR are present in the endosome or on the cellular membrane and can sense the aberrant release of nucleic acids, which is often a sign of acute or chronic cellular damage. Absent in melanoma 2 (AIM2) is a PRR that is expressed by vascular cells and specializes in detecting cytoplasmic double-stranded DNA (dsDNA). Activation of AIM2 leads eventually to activation of the inflammasome, but the role of AIM2 in vascular disease and atherosclerosis has not been well-studied. Therefore, in this study we took advantage of acute and chronic models of vascular injury to determine the biological role of AIM2 in atherogenesis. We were able to induce significant release of proinflammatory cytokines in mice through the intravenous injection of a synthetic ligand for AIM2, double-stranded poly dA:dT. This cytokine release was shown to impair reendothelialization of the carotid artery and increase the number of circulating endothelial microparticles (EMP) after acute denudation, compared to treatment with vehicle. We saw an increase in the production of reactive oxygen species in the aorta, the number of circulating EMP, and, most interestingly, atherosclerotic plaque formation in apolipoprotein E-deficient (ApoE) mice when they received continual subcutaneous poly dA:dT, in contrast to vehicle-treated animals. Finally, treatment with poly dA:dT did not impair vascular reendothelialization in AIM2 mice compared to vehicle controls in the carotid artery injury model. Overall, our data suggest that AIM2, as a known regulator of the inflammasome, is an active participant in atherogenesis, and highlight the importance of fully understanding the pathological mechanisms involved. It seems to be worth of further exploration as a therapeutic target, and future studies focusing on the effects of AIM2 activation as well as its pharmacological inhibition may reveal promising new therapeutic concepts for the treatment of atherosclerosis.
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http://dx.doi.org/10.3389/fcvm.2020.582482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685997PMC
November 2020

Hospital admissions during Covid-19 lock-down in Germany: Differences in discretionary and unavoidable cardiovascular events.

PLoS One 2020 20;15(11):e0242653. Epub 2020 Nov 20.

Department of Cardiology, Heart Center, University of Bonn, Bonn, Germany.

Background: A decline in hospitalization for cardiovascular events and catheter laboratory activation was reported for the United States and Italy during the initial stage of the Covid-19 pandemic of 2020. We report on the deployment of emergency services for cardiovascular events in a defined region in western Germany during the government-imposed lock-down period.

Methods: We examined 5799 consecutive patients who were treated by emergency services for cardiovascular events during the Covid-19 pandemic (January 1 to April 30, 2020), and compared those to the corresponding time frame in 2019. Examining the emergency physicians' records provided by nine locations in the area, we found a 20% overall decline in cardiovascular admissions.

Results: The greatest reduction could be seen immediately following the government-imposed social restrictions. This reduction was mainly driven by a reduction in discretionary admissions for dizziness/syncope (-53%), heart failure (-38%), exacerbated COPD (-28%) and unstable angina (-23%), while unavoidable admissions for ST-elevation myocardial infarction (STEMI), cardiopulmonary resuscitation (CPR) and stroke were unchanged. There was a greater decline in emergency admissions for patients ≥60 years. There was also a greater reduction in emergency admissions for those living in urban areas compared to suburban areas.

Conclusions: During the Covid-19 pandemic, a significant decline in hospitalization for cardiovascular events was observed during the government-enforced shutdown in a predefined area in western Germany. This reduction in admissions was mainly driven by "discretionary" cardiovascular events (unstable angina, heart failure, exacerbated COPD and dizziness/syncope), but events in which admission was unavoidable (CPR, STEMI and stroke) did not change.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242653PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678984PMC
December 2020

Association of heart failure duration with clinical outcomes after transcatheter mitral valve repair for functional mitral regurgitation.

Catheter Cardiovasc Interv 2020 Nov 19. Epub 2020 Nov 19.

Heart Center Bonn, Department of Medicine II, University Hospital Bonn, Bonn, Germany.

Background: Little is known about the association of heart failure (HF) chronicity with clinical outcomes after transcatheter mitral valve repair (TMVR) for functional mitral regurgitation (MR).

Methods: From January 2011 to March 2019, consecutive patients with functional MR who underwent a MitraClip procedure were analyzed. The patients were divided into two groups according to HF duration-those with duration ≤18 months and those with >18 months. The primary outcome measure was a composite of all-cause mortality and re-HF rehospitalization within 1 year after the procedure. These outcomes were also assessed separately. A Cox proportional hazard model was conducted for investigating the association of HF duration with the primary outcome.

Results: A total of 208 patients were analyzed. Patients with HF duration >18 months had a higher rate of the primary outcome compared to those with HF duration ≤18 months (38.1 vs. 19.0%, log-rank p = .003). A longer duration of HF was associated with an increased risk of the primary outcomes (adjusted-HR of >18 months, 2.12 95% CI, 1.14-4.19; p = .03; adjusted-HR (hazard ratios) for 1 year increase, 1.05; 95% CI, 1.02-1.09; p = .004). The association of HF duration with the primary outcomes showed a steep rise during the first 2 years of HF duration and progressive increase after 5 years.

Conclusions: A longer HF duration before TMVR was associated with an increased risk of all-cause mortality or HF rehospitalization. HF duration can be used for the risk stratification marker in patients undergoing TMVR for functional MR.
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http://dx.doi.org/10.1002/ccd.29390DOI Listing
November 2020

Impact of cancer history on clinical outcome in patients undergoing transcatheter edge-to-edge mitral repair.

Clin Res Cardiol 2021 Mar 9;110(3):440-450. Epub 2020 Nov 9.

Department of Medicine II, Heart Center Bonn, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: Little is known about the prevalence of a history of cancer and its impact on clinical outcome in mitral regurgitation (MR) patients undergoing transcatheter mitral valve repair (TMVR).

Objectives: The purpose of this study is to investigate the prevalence of cancer, baseline inflammatory parameters, and clinical outcome in MR patients undergoing TMVR.

Methods: Consecutive patients undergoing a MitraClip procedure were enrolled, and the patients were stratified into two groups: cancer and non-cancer. Baseline complete blood counts (CBC) with differential hemograms were collected prior to the procedure to calculate the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR). All-cause death within a one-year was examined.

Results: In total, 82 out of 446 patients (18.4%) had a history of cancer. Cancer patients had a significantly higher baseline PLR [181.4 (121.1-263.9) vs. 155.4 (109.4-210.4); P = 0.012] and NLR [5.4 (3.5-8.3) vs. 4.0 (2.9-6.1); P = 0.002] than non-cancer patients. A Kaplan-Meier analysis revealed that cancer patients had a significantly worse prognosis than non-cancer (estimated 1-year mortality, 20.2 vs. 9.2%; log-rank P = 0.009), and multivariable analyses of three models showed that cancer history was an independent factor for 1-year mortality. Patients who died during follow-up had a significantly higher baseline PLR [214.2 (124.2-296.7) vs. 156.3 (110.2-212.1); P = 0.007] and NLR [6.4 (4.2-12.5) vs. 4.0 (2.9-6.2); P < 0.001] than survivors.

Conclusions: In MitraClip patients, a history of cancer was associated with higher inflammatory parameters and worse prognosis compared to non-cancer patients. Central Illustration. Clinical outcomes and baseline PLR and NLR values accord-ing to one-year mortality. (Left) Patients who died within the follow-up period had a significantly higher baseline PLR (214.2 [124.2-296.7] vs 156.3 [110.2-212.1]; P = 0.007) and NLR (6.4 [4.2-12.5] vs 4.0 [2.9-6.2]; P < 0.001) than patients who survived. PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio (Right) A Kaplan-Meier analysis revealed that cancer patients had a significantly worse prognosis than non-cancer patients (estimated one-year mortality, 20.2 vs 9.2%; log-rank P = 0.009).
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http://dx.doi.org/10.1007/s00392-020-01770-2DOI Listing
March 2021

Dual antithrombotic therapy with dabigatran in patients with atrial fibrillation after percutaneous coronary intervention for ST elevation myocardial infarction: results from the randomised RE-DUAL PCI trial.

EuroIntervention 2020 Nov 10. Epub 2020 Nov 10.

Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Ludwigshafen, Germany.

Aims: To investigate the safety and efficacy of dabigatran dual therapy (110 or 150 mg twice daily, plus clopidogrel or ticagrelor) vs warfarin triple therapy in patients with atrial fibrillation undergoing PCI for ST elevation myocardial infarction (STEMI).

Methods And Results: In RE-DUAL PCI, 305 patients with STEMI were randomised to dabigatran 110 mg (n=113 versus 106 warfarin) or 150 mg (n=86 versus 84 warfarin). Primary endpoint was time to first major or clinically relevant non-major bleeding event (MBE/CRNMBE). The thrombotic endpoint was a composite of death, thromboembolic events, or unplanned revascularisation. In STEMI patients, dabigatran 110 mg (HR 0.39, 95% CI 0.20-0.74) and 150 mg (0.43, 0.21-0.89) dual therapy reduced the risk of MBE/CRNMBE versus warfarin triple therapy (p interaction vs all other patients = 0.31 and 0.16). Risk of thrombotic events, for dabigatran 110 mg (HR 1.61, 95% CI: 0.85-3.08) and 150 mg (0.56, 0.20-1.51) had p interactions of 0.20 and 0.33, respectively. For net clinical benefit, HRs were 0.74 (95% CI 0.46-1.17) and 0.49 (0.27-0.91) for dabigatran 110 and 150 mg (p interaction = 0.80 and 0.12).

Conclusions: In patients after PCI for STEMI, dabigatran dual therapy had lower risks of bleeding events versus warfarin triple therapy with similar risks of thromboembolic events, supporting the use of dabigatran dual therapy even in patients with high thrombotic risk.
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http://dx.doi.org/10.4244/EIJ-D-20-00799DOI Listing
November 2020

Procedural and clinical outcomes of type 0 versus type 1 bicuspid aortic valve stenosis undergoing trans-catheter valve replacement with new generation devices: Insight from the BEAT international collaborative registry.

Int J Cardiol 2021 Feb 22;325:109-114. Epub 2020 Oct 22.

GVM Care and Research, Maria Cecilia Hospital, Cotignola, Ravenna, Italy; EMO GVM Centro Cuore Columbus, Milan, Italy.

Background: Although bicuspid aortic valve (BAV) is not considered a "sweet spot" to trans-catheter aortic valve replacement (TAVR), a certain number of BAV underwent TAVR. Whether BAV phenotype affects outcomes following TAVR remains debated. We aimed at evaluating the impact of BAV phenotype on procedural and clinical outcomes after TAVR using new generation trans-catheter heart valves (THVs).

Methods: patients included in the BEAT registry were classified according to the BAV phenotype revealed at multi-slice computed tomography (MSCT) in type 0 (no raphe) vs. type 1 (1 raphe). Primary end-point was Valve Academic Research Consortium-2 (VARC-2) device success. Secondary end-points included procedural complications, rate of permanent pacemaker implantation, clinical outcomes at 30-day and 1-year.

Results: Type 0 BAV was present in 25(7.1%) cases, type 1 in 218(61.8%). Baseline characteristics were well balanced between groups. Moderate-severe aortic valve calcifications at MSCT were less frequently present in type 0 vs. type 1 (52%vs.71.1%,p = 0.05). No differences were reported for THV type, size, pre and post-dilation between groups. VARC-2 success tended to be lower in type 0 vs. type 1 BAV (72%vs86.7%;p = 0.07). Higher rate of mean transprosthetic gradient ≥20 mmHg was observed in type 0 vs. type 1 group (24%vs6%,p = 0.007). No differences were reported in the rate of post-TAVR moderate-severe aortic regurgitation and clinical outcomes between groups.

Conclusions: Our study confirms TAVR feasibility in both BAV types, however a trend toward a lower VARC-2 device success and a higher rate of mean transprosthetic gradient ≥20 mmHg was observed in type 0 vs. type 1 BAV.
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http://dx.doi.org/10.1016/j.ijcard.2020.10.050DOI Listing
February 2021

MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease.

Cardiovasc Res 2020 Nov 2. Epub 2020 Nov 2.

Department of Internal Medicine II, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Aims: Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease (CAD). For both, CKD and CAD, the intercellular transfer of microRNAs (miR) through extracellular vesicles (EVs) is an important factor of disease development. Whether the combination of CAD and CKD affects endothelial function through cellular crosstalk of EV-incorporated miRs is still unknown.

Methods And Results: Out of 172 screened CAD patients, 31 patients with CAD+CKD were identified and matched with 31 CAD patients without CKD. Additionally, 13 controls without CAD and CKD were included. Large EVs from CAD+CKD patients contained significantly lower levels of the vasculo-protective miR-130a-3p and miR-126-3p compared to CAD patients and controls. Flow cytometric analysis of plasma-derived EVs revealed significantly higher numbers of endothelial cell-derived EVs in CAD and CAD+CKD patients compared to controls. EVs from CAD+CKD patients impaired target human coronary artery endothelial cell (HCAEC) proliferation upon incubation in vitro. Consistent with the clinical data, treatment with the uremia toxin indoxyl sulfate (IS) reduced miR-130a-3p levels in HCAEC-derived EVs. EVs from IS-treated donor HCAECs reduced proliferation and reendothelialization in EV-recipient cells and induced an anti-angiogenic gene expression profile. In a mouse-experiment, intravenous treatment with EVs from IS-treated endothelial cells significantly impaired endothelial regeneration. On the molecular level, we found that IS leads to an upregulation of the heterogenous nuclear ribonucleoprotein U (hnRNPU), which retains miR-130a-3p in the cell leading to reduced vesicular miR-130a-3p export and impaired EV-recipient cell proliferation.

Conclusions: Our findings suggest that EV-miR-mediated vascular intercellular communication is altered in patients with CAD and CKD, promoting CKD-induced endothelial dysfunction.

Translational Perspective: In the present study we identify a novel hnRNPU-dependent mechanism of how kidney disease and uremia reduce endothelial proliferation. HnRNPU can therefore be used as a target to influence vesicular microRNA levels to improve endothelial healing.
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http://dx.doi.org/10.1093/cvr/cvaa322DOI Listing
November 2020

Risk of mortality following transcatheter aortic valve replacement for low-flow low-gradient aortic stenosis.

Clin Res Cardiol 2021 Mar 14;110(3):391-398. Epub 2020 Oct 14.

Heart Center Bonn, Department of Medicine II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: Low-flow low-gradient (LF-LG) aortic stenosis (AS) is associated with high mortality, even after transcatheter aortic valve replacement (TAVR). Further knowledge of risk indicators is needed and a clinical risk score would be desirable for optimizing patient selection and therapeutic strategy.

Methods: The study cohort comprised of 219 consecutive LF-LG AS patients undergoing TAVR from 2008 to 2018 in two high-volume German centers. Predictive factors for one-year all-cause mortality were defined according to a Cox proportional hazard model.

Results: At one-year follow-up after TAVR, 28% of patients had died. A multivariate model revealed six independent predictors of one-year mortality: history of myocardial infarction (HR 2.05, 95%CI 1.13-3.72), eGFR < 30 ml/min/1.73m (HR 2.75, 95%CI 1.48-5.11), tricuspid regurgitation moderate or more (HR 2.06, 95%CI 1.14-3.72), stroke volume index < 25 mL/m (HR 2.03, 95%CI 1.14-3.62), self-expandable device (HR 2.72, 95%CI 1.17-6.27), and non-transfemoral approach (HR 3.42, 95%CI 1.28-9.14). The Rhineland Risk Score (RRS) consisting of these variables (c statistic 0.75, 95%CI 0.68-0.82, p < 0.001) was superior to the EuroSCORE II (c statistic 0.63) and STS-PROM score (c statistic 0.69) at predicting one-year mortality. Patients with a RRS ≥ 8 had a prohibitive risk of one-year mortality of 67.6% (95%CI 52.0-82.4%).

Conclusion: In patients with LF-LG AS, history of myocardial infarction, renal dysfunction, tricuspid regurgitation, a low stroke volume index, self-expandable device, and non-femoral approach were associated with increased 1-year mortality after TAVR. The RRS might serve as a helpful tool for risk prediction and patient selection for TAVR in patients with LF-LG AS.
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http://dx.doi.org/10.1007/s00392-020-01752-4DOI Listing
March 2021

Tricuspid valve repair with the Cardioband system: two-year outcomes of the multicentre, prospective TRI-REPAIR study.

EuroIntervention 2021 Feb 5;16(15):e1264-e1271. Epub 2021 Feb 5.

University Hospital Bonn, Bonn, Germany.

Aims: Tricuspid regurgitation (TR) is associated with high morbidity and mortality rates with limited treatment options. We report one- and two-year outcomes of the Cardioband tricuspid valve reconstruction system in the treatment of ≥moderate functional TR in the TRI-REPAIR study.

Methods And Results: Thirty patients were enrolled in this single-arm, multicentre, prospective study. Patients were evaluated as having ≥moderate, symptomatic functional TR and deemed inoperable due to unacceptable surgical risk. Clinical, functional, and echocardiographic data were prospectively collected up to two years (mean duration 604±227 days). At baseline, 83% were in NYHA Class III-IV, and the mean LVEF was 58%. Technical success was 100%. At two years, there were eight deaths. Echocardiography showed a significant reduction in septolateral annular diameter of 16% (p=0.006) and 72% of patients (p=0.016) with ≤moderate TR grade; 82% of patients were in NYHA Class I-II (p=0.002). Six-minute walk distance and KCCQ score improved by 73 m (p=0.058) and 14 points (p=0.046), respectively.

Conclusions: These results demonstrate that the Cardioband tricuspid system showed favourable results in patients with symptomatic, ≥moderate functional TR. Annular reduction and TR severity reduction remained significant and sustained at two years. Patients experienced improvements in quality of life and exercise capacity. ClinicalTrials.gov Identifier: NCT02981953.
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http://dx.doi.org/10.4244/EIJ-D-20-01107DOI Listing
February 2021

Impact of Coronary Artery Disease on Outcomes in Patients Undergoing Percutaneous Edge-to-Edge Repair.

JACC Cardiovasc Interv 2020 Sep;13(18):2137-2145

Department of Cardiology, University Hospital Bonn, Bonn, Germany. Electronic address:

Objectives: The aim of this observational study was to evaluate the impact of concomitant coronary artery disease (CAD) on outcomes in patients undergoing percutaneous valve repair with the MitraClip system.

Background: Mitral valve regurgitation and CAD are often coexistent in elderly patients undergoing percutaneous mitral valve repair. The impact of CAD and revascularization on outcomes in this patient cohort, however, remains uncertain.

Methods: In 444 MitraClip patients, CAD severity was assessed, represented by the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS), as well as the residual SS (rSS) and SYNTAX score II (SS-II). Patients were stratified according to CAD severity and SS-II values (SS ≤3 vs. SS >3 and SS-II ≤45 vs. SS-II >45) and according to remaining CAD burden into 2 groups (rSS = 0 vs. rSS >0) to compare 1-year all-cause mortality.

Results: Higher SS, rSS, and SS-II were associated with mortality (22% for SS >3 vs. 9.6% for SS ≤3 [p < 0.001], 31.4% for rSS >0 vs. 9.6% for rSS = 0 [p < 0.001], and 17.1% for SS-II > 45 vs. 11.2% for SS-II ≤45 [p = 0.044]). The rSS was an independent predictor of 1-year all-cause mortality (p = 0.001) in multivariate analysis.

Conclusions: The complexity of CAD, as assessed using the SS, is associated with outcomes in patients undergoing MitraClip procedures. The burden of residual CAD after percutaneous coronary intervention is an independent predictor of 1-year all-cause mortality. Patients undergoing complete revascularization had the most favorable outcomes independent of mitral regurgitation etiology.
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http://dx.doi.org/10.1016/j.jcin.2020.05.031DOI Listing
September 2020

The RNA-binding protein hnRNPU regulates the sorting of microRNA-30c-5p into large extracellular vesicles.

J Extracell Vesicles 2020 Jul 2;9(1):1786967. Epub 2020 Jul 2.

Heart Center Bonn, Medical Department II, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany.

The transfer of microRNAs (miRs) via extracellular vesicles (EVs) is a functionally relevant mechanism of intercellular communication that regulates both organ homoeostasis and disease development. Little is known about the packaging of miRs into EVs. Previous studies have shown that certain miRs are exported by RNA-binding proteins into small EVs, while for other miRs and for large EVs, in general, the export mechanisms remain unclear. Therefore, a proteomic analysis of endothelial cell-derived large EVs was performed, which revealed that heterogeneous nuclear ribonucleoprotein U (hnRNPU) is abundantly present in EVs. EVs were characterized by electron microscopy, immunoblotting and nanoparticle tracking analysis. Taqman microRNA array and single qPCR experiments identified specific miR patterns to be exported into EVs in an hnRNPU-dependent way. The specific role of hnRNPU for vesicular miR-sorting was confirmed independently by gain- and loss-of-function experiments. In our study, miR-30c-5p was the miR whose export was most significantly regulated by hnRNPU. Mechanistically, binding analysis showed that the export of miRs into EVs depends on the binding efficiency of the respective miRs to hnRNPU. Among the exported miRs, a significant enrichment of the sequence motif AAMRUGCU was detected as a potential sorting signal. Experimentally, binding of miR-30c-5p to hnRNPU was confirmed independently by RNA-immunoprecipitation, electrophoretic mobility shift assay and reciprocally by miR-pulldown. Nuclear binding of miR-30c-5p to hnRNPU and subsequent stabilization was associated with a lower cytoplasmatic abundance and consequently reduced availability for vesicular export. hnRNPU-dependent miR-30c-5p export reduced cellular migration as well as pro-angiogenic gene expression in EV-recipient cells. In summary, hnRNPU retains miR-30c-5p and other miRs and thereby prevents their export into large EVs. The data presented provide a novel and functionally relevant mechanism of vesicular miR export.
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http://dx.doi.org/10.1080/20013078.2020.1786967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480565PMC
July 2020

Prognostic value of myeloperoxidase in patients with peripheral artery disease.

Vascular 2020 Sep 14:1708538120957491. Epub 2020 Sep 14.

Department of Medicine II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany.

Objectives: The involvement of myeloperoxidase in the production of dysfunctional high-density lipoproteins and oxidised biomolecules leads to oxidative stress in the blood vessel endothelium. This prospective cohort study aimed to examine the prognostic value of myeloperoxidase in patients with peripheral artery disease in relation to major adverse cardiac events (MACEs), target lesion revascularisation, and major adverse limb events (MALEs) and its association with multi-bed vascular disease, which is defined as any combination of the following: peripheral artery disease and coronary artery disease.

Methods: Myeloperoxidase levels were measured in patients with peripheral artery disease and coronary artery disease during angiography. A total of 94 patients were analysed and followed up regarding their MACEs, target lesion revascularisation, and MALEs from August 2016 until February 2019.

Results: Among patients with peripheral artery disease, the rates of MACE and mortality were higher in patients with high myeloperoxidase levels than in those with low myeloperoxidase levels; the myeloperoxidase levels were 3.68 times higher in these patients ( < 0.0001). Patients with peripheral artery disease and coronary artery disease (multi-bed vascular disease) had higher myeloperoxidase levels than those with only peripheral artery disease and only coronary artery disease (one-bed vascular disease). Peripheral artery disease patients with higher myeloperoxidase levels had significantly higher rates of limb ischaemia, requiring further revascularisation than those with low myeloperoxidase levels.

Conclusions: High myeloperoxidase levels suggest poor outcomes and are associated with MACE and limb ischaemia. Our findings indicated that myeloperoxidase levels could become a prognostic marker and may be used in conjunction with other methods for risk stratification in patients with peripheral artery disease and multi-bed vascular disease.
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http://dx.doi.org/10.1177/1708538120957491DOI Listing
September 2020

Impact of Massive or Torrential Tricuspid Regurgitation in Patients Undergoing Transcatheter Tricuspid Valve Intervention.

JACC Cardiovasc Interv 2020 09;13(17):1999-2009

Department of Cardiac Surgery, University Hospital Zurich, Zurich, Switzerland. Electronic address:

Objectives: The aim of this study was to assess the clinical outcome of baseline massive or torrential tricuspid regurgitation (TR) after transcatheter tricuspid valve intervention (TTVI).

Background: The use of TTVI to treat symptomatic severe TR has been increasing rapidly, but little is known regarding the impact of massive or torrential TR beyond severe TR.

Methods: The study population comprised 333 patients with significant symptomatic TR from the TriValve Registry who underwent TTVI. Mid-term outcomes after TTVI were assessed according to the presence of massive or torrential TR, defined as vena contracta width ≥14 mm. Procedural success was defined as patient survival after successful device implantation and delivery system retrieval, with residual TR ≤2+. The primary endpoint comprised survival rate and freedom from rehospitalization for heart failure, survival rate, and rehospitalization at 1 year.

Results: Baseline massive or torrential TR and severe TR were observed in 154 patients (46.2%) and 179 patients (53.8%), respectively. Patients with massive or torrential TR had a higher prevalence of ascites than those with severe TR (27.3% vs. 20.4%, respectively; p = 0.15) and demonstrated a similar procedural success rate (83.2% vs. 77.3%, respectively; p = 0.21). The incidence of peri-procedural adverse events was low, with no significant between-group differences. Freedom from the composite endpoint was significantly lower in patients with massive or torrential TR than in those with severe TR, which was significantly associated with an increased risk for 1-year death of any cause or rehospitalization for heart failure (adjusted hazard ratio: 1.91; 95% confidence interval: 1.10 to 3.34; p = 0.022). Freedom from the composite endpoint was significantly higher in patients with massive or torrential TR when procedural success was achieved (69.9% vs. 54.2%, p = 0.048).

Conclusions: Baseline massive or torrential TR is associated with an increased risk for all-cause mortality and rehospitalization for heart failure 1 year after TTVI. Procedural success is related to better outcomes, even in the presence of baseline massive or torrential TR. (International Multisite Transcatheter Tricuspid Valve Therapies Registry [TriValve]; NCT03416166).
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http://dx.doi.org/10.1016/j.jcin.2020.05.011DOI Listing
September 2020

Risk modeling in transcatheter aortic valve replacement remains unsolved: an external validation study in 2946 German patients.

Clin Res Cardiol 2021 Mar 26;110(3):368-376. Epub 2020 Aug 26.

Division of Cardiology, Pulmonology and Vascular Medicine, Department of Internal Medicine, Heinrich Heine University, Medical Faculty, Moorenstr. 5, 40225, Düsseldorf, Germany.

Background: Surgical risk prediction models are routinely used to guide decision-making for transcatheter aortic valve replacement (TAVR). New and updated TAVR-specific models have been developed to improve risk stratification; however, the best option remains unknown.

Objective: To perform a comparative validation study of six risk models for the prediction of 30-day mortality in TAVR METHODS AND RESULTS: A total of 2946 patients undergoing transfemoral (TF, n = 2625) or transapical (TA, n = 321) TAVR from 2008 to 2018 from the German Rhine Transregio Aortic Diseases cohort were included. Six surgical and TAVR-specific risk scoring models (LogES I, ES II, STS PROM, FRANCE-2, OBSERVANT, GAVS-II) were evaluated for the prediction of 30-day mortality. Observed 30-day mortality was 3.7% (TF 3.2%; TA 7.5%), mean 30-day mortality risk prediction varied from 5.8 ± 5.0% (OBSERVANT) to 23.4 ± 15.9% (LogES I). Discrimination performance (ROC analysis, c-indices) ranged from 0.60 (OBSERVANT) to 0.67 (STS PROM), without significant differences between models, between TF or TA approach or over time. STS PROM discriminated numerically best in TF TAVR (c-index 0.66; range of c-indices 0.60 to 0.66); performance was very similar in TA TAVR (LogES I, ES II, FRANCE-2 and GAVS-II all with c-index 0.67). Regarding calibration, all risk scoring models-especially LogES I-overestimated mortality risk, especially in high-risk patients.

Conclusions: Surgical as well as TAVR-specific risk scoring models showed mediocre performance in prediction of 30-day mortality risk for TAVR in the German Rhine Transregio Aortic Diseases cohort. Development of new or updated risk models is necessary to improve risk stratification.
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http://dx.doi.org/10.1007/s00392-020-01731-9DOI Listing
March 2021

The endocannabinoid 2-arachidonoylglycerol inhibits endothelial function and repair.

Int J Cardiol 2021 Jan 15;323:243-250. Epub 2020 Aug 15.

Department of Internal Medicine II Cardiology, Pneumology, Angiology, University Hospital Bonn, Venusberg-Campus 1, Bonn 53127, Germany.

Background: Endothelial dysfunction promotes atherogenesis, vascular inflammation, and thrombus formation. Reendothelialization after angioplasty is required in order to prevent stent failure. Previous studies have highlighted the role of 2-arachidonoylglycerol (2-AG) in murine experimental atherogenesis and in human coronary artery disease. However, the impact of 2-AG on endothelial repair and leukocyte-endothelial cell adhesion is still unknown.

Methods: Endothelial repair was studied in two treatment groups of wildtype mice following electrical injury of the common carotid artery. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184, which impairs 2-AG degradation and thus causes elevated 2-AG levels, the other group received DMSO (vehicle). The effect of 2-AG on human coronary artery endothelial cell (HCAEC) viability, leukocyte-endothelial cell adhesion, surface expression of adhesion molecules, and expression of endothelial NO synthase (NOS3) was studied in vitro.

Results: Elevated 2-AG levels significantly impaired reendothelialization in wildtype mice following electrical injury of the common carotid artery. In vitro, 2-AG significantly reduced viability of HCAEC. Additionally, 2-AG promoted adhesion of THP-1 monocytes to HCAEC following pre-treatment of the HCAEC with 2-AG. Adhesion molecules (E-selectin, ICAM-1 and VCAM-1) remained unchanged in arterial endothelial cells, whereas 2-AG suppressed the expression of NOS3 in HCAEC.

Conclusion And Translational Aspect: Elevated 2-AG levels hamper endothelial repair and HCAEC proliferation, while simultaneously facilitating leukocyte-endothelial cell adhesion. Given that 2-AG is elevated in patients with coronary artery disease and non-ST-segment elevation myocardial infarction, 2-AG might decrease reendothelialization after angioplasty and thus impact the clinical outcomes.
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http://dx.doi.org/10.1016/j.ijcard.2020.08.042DOI Listing
January 2021