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BACKGROUND: Bioprosthetic valve thrombosis may have implications for valve function and durability.OBJECTIVES: Using a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves.METHODS: Ex vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT.RESULTS: Flow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake.CONCLUSIONS: Adherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875).

Background Severe tricuspid regurgitation (TR) has limited treatment options and is associated with high morbidity and mortality. Aims We evaluated the safety and effectiveness of the Cardioband tricuspid valve reconstruction system (Edwards Lifesciences, Irvine, CA, USA) from the ongoing European single-arm, multicentre, prospective TriBAND post-market clinical follow-up study. Methods Eligible patients had chronic symptomatic functional TR despite diuretic therapy and were deemed candidates for transcatheter tricuspid repair by the local Heart Team. Results Sixty-one patients had ≥severe functional TR. At baseline, 85% of patients were in NYHA Class III-IV, 94% had ≥severe TR (core laboratory-assessed) with 6.8% EuroSCORE II and 53% LVEF. Device success was 96.7%. At discharge, 59% (pl0.001) of patients achieved ≤moderate TR and 78% had at least one grade TR reduction. At 30 days, all-cause mortality and composite MAE rates were 1.6% and 19.7%, respectively; septolateral annular diameter was reduced by 20%, where 69% of patients achieved ≤moderate TR and 85% of patients had at least one grade TR reduction (all pl0.001). Mid-RVEDD, RA volume, and IVC diameter decreased by 10% (p=0.005), 21% (pl0.001), and 11% (p=0.022), respectively; 74% were in NYHA Class I-II (pl0.001) with improvements in overall KCCQ score by 17 points (pl0.001). Conclusions In the TriBAND study, the Cardioband tricuspid system demonstrated favourable outcomes at discharge and 30 days in a challenging patient population with symptomatic ≥severe functional TR. Results showed significant reductions in annular diameter and TR severity, accompanied by early evidence of right heart remodelling and improvements in functional status and quality of life.

BACKGROUND The Cardioband tricuspid valve reconstruction system is a size-adjustable tricuspid reconstruction device for interventional treatment of tricuspid regurgitation (TR). Contraction of the device after successful implantation can be associated with an acute deformation of the right coronary artery (RCA). AIMS The aim of this study was to provide data on the persistence and clinical significance of acute RCA deformation following Cardioband implant procedures. METHODS Data from all patients with intraprocedural RCA deformation during Cardioband implantation were collected from four centres between October 2018 and January 2020. Control angiographies were performed in all of these patients before discharge. RESULTS RCA deformation occurred in 14 out of 51 patients. Follow-up coronary angiography showed a complete resolution of deformation in all cases while patients remained clinically asymptomatic and had an uneventful post-interventional course. Intraprocedural coronary stent implantation was performed in two of the earlier cases according to the personal assessment of the implanters. CONCLUSIONS RCA deformation is relatively frequent following interventional tricuspid annuloplasty but appears to be completely reversible in the absence of flow impairment or vascular damage. Based on our early experience watchful waiting is the most appropriate strategy to avoid unnecessary coronary interventions.

Background The PASCAL system is a novel device for edge-to-edge treatment of mitral regurgitation (MR). The aim of this study was to compare the safety and efficacy of the PASCAL to the MitraClip system in a highly selected group of patients with complex primary mitral regurgitation (PMR) defined as effective regurgitant orifice area (MR-EROA) ≥ 0.40 cm2, large flail gap (≥ 5 mm) or width (≥ 7 mm) or Barlow’s disease. Methods 38 patients with complex PMR undergoing mitral intervention using PASCAL (n = 22) or MitraClip (n = 16) were enrolled. Primary efficacy endpoints were procedural success and degree of residual MR at discharge. The rate of major adverse events (MAE) according to the Mitral Valve Academic Consortium (MVARC) criteria was chosen as the primary safety endpoint. Results Patient collectives did not differ relevantly regarding pertinent baseline parameters. Patients` median age was 83.0 [77.5–85.3] years (PASCAL) and 82.5 [76.5–86.5] years (MitraClip). MR-EROA at baseline was 0.70 [0.68–0.83] cm2 (PASCAL) and 0.70 [0.50–0.90] cm2 (MitraClip), respectively. 3D-echocardiographic morphometry of the mitral valve apparatus revealed no relevant differences between groups. Procedural success was achieved in 95.5% (PASCAL) and 87.5% (MitraClip), respectively. In 86.4% of the patients a residual MR grade ≤ 1 + was achieved with PASCAL whereas reduction to MR grade ≤ 1 + with MitraClip was achieved in 62.5%. Neither procedure time number of implanted devices, nor transmitral gradient differed significantly. No periprocedural MAE according to MVARC occured. Conclusion In this highly selected patient group with complex PMR both systems exhibited equal procedural safety. MitraClip and PASCAL reduced qualitative and semi-quantitative parameters of MR to an at least comparable extent. Graphic abstract

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

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.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.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).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%).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.

Objectives and background Percutaneous edge-to-edge mitral valve (MV) repair (PMVR) is broadly applied in high-risk patients with relevant mitral regurgitation (MR). We investigated the incidence of cleft-like indentations (CLI) and their impact on PMVR. Methods and results In a retrospective single center analysis including 263 patients undergoing PMVR with the MitraClip®-system between 11/2012 and 7/2016, MV anatomy was assessed by 3-dimensional transesophageal echocardiography. CLI were present in 37/263 patients (14.1%). Of these, 62.2% had 1 CLI, 27% had 2 CLI, and 10.8% had 3 CLI, mostly concerning segment P2 or P2/3 of the MV. Baseline characteristics were similarly distributed. Interestingly, most patients with CLI suffered from secondary MR (n = 29, 78%). The number of deployed MitraClips was higher in patients with CLI (2 [1.25-2] vs. 2 [1, 2], p = .035), whereas procedural as well as clinical success was similar: MR grade (1.2 vs. 1.5, p = .061), vena contracta width (4.2 vs. 4.5 mm, p = .293), dPmean (4.2 vs. 4.0 mmHg, p = .618) at discharge and NYHA class at 30 days did not differ between groups. Periprocedural complications were rare and equally distributed between groups. At 30 days, MR reduction persisted in patients with CLI (95.8% of these selected patients had a MR grade ≤ 2). Conclusions CLI of the MV are common in patients undergoing PMVR, also when presenting mainly with secondary MR. While the number of clips needed to address MR is slightly higher in patients with CLI, procedural success rates appear not to be affected. PMVR seems to be a safe treatment option for patients with CLI.

Background: Severe tricuspid regurgitation (TR) is independently associated with increased morbidity and mortality. Percutaneous transcatheter approaches may offer an alternative for patients not amenable to surgery. Methods: TriCLASP is a prospective, single-arm, multicenter European post-market clinical follow-up study (NCT04614402) to evaluate the safety and performance of the PASCAL system (Edwards Lifesciences) in patients with severe or greater TR. At 30 days, a composite of major adverse events (MAEs) adjudicated by a clinical events committee, echocardiographic parameters adjudicated by core laboratory, and clinical, functional, and quality-of-life measures were evaluated. Results: Mean age of the 74 enrolled patients was 80.3 years, with 58.1% female, 90.5% systemic hypertension, and 77.0% in New York Heart Association (NYHA) class III/IV. Mean Society for Thoracic Surgeons score (MV repair) was 9.0%. TR severity was significantly reduced at discharge (p < 0.001) and sustained at 30 days (p < 0.001), and 90.0% of patients achieved ≤moderate TR. The composite MAE rate at 30 days was 3.0%, including 4 events in 2 patients: cardiovascular mortality 1.5%, stroke 1.5%, renal complications requiring unplanned dialysis or renal replacement therapy 1.5%, and severe bleeding 1.5%. There were no nonelective tricuspid valve reinterventions, major access site and vascular complications, major cardiac structural complications, or device embolizations. NYHA class I/II was achieved in 55.8%, 6-minute walk distance improved by 38.2 m (p < 0.001), and Kansas City cardiomyopathy questionnaire scores improved by 13.4 points (p < 0.001). Conclusion: Experience with the PASCAL transcatheter valve repair system in a European post-market setting confirms favorable safety and effectiveness at 30 days. TR significantly reduced, and clinical, functional, and quality-of-life outcomes significantly improved. This study is ongoing. Clinical Trial Registration: The study is ongoing and registered on ClinicalTrials.gov as NCT04614402. The current analysis is an interim report.

Background/Introduction Bioprosthetic valve thrombosis (BPVT) is an important clinical entity eventually following both bioprosthetic surgical and transcatheter aortic valve replacement. Although dynamic contrast-enhanced 4D-MDCT has improved the diagnosis of BPVT, more sensitive and pathology-specific non-invasive imaging tools are lacking. Recently, the glycoprotein IIb/IIIa receptor targeted, elarofiban-derived PET/CT imaging radiotracer [18F]GP1 has been successfully used for visualization of acute venous and arterial thrombi. Purpose We hypothesized that [18F]GP1 PET/CT imaging is suitable to detect BPVT. Methods In this proof-of-concept study, patients after bioprosthetic aortic valve replacement with symptomatic, severe hemodynamic valve dysfunction and confirmed hypoattenuated leaflet thickening (HALT) in dynamic 4D-MDCT were offered to participate in compassionate use examinations to undergo PET/CT imaging with the investigational [18F]GP1 PET tracer at baseline and after a 12-week course of therapeutic oral anticoagulation. Results This case series reports on three patients after aortic valve replacement. Two patients with symptomatic, obstructive BPVT as confirmed by echocardiography and 4D-MDCT fulfilled specified criteria and underwent [18F]GP1 PET/CT imaging. [18F]GP1 PET/CT clearly distinguished between blood pool activity and thrombotic foci. Clot-to-blood ratios at baseline were 8.2 and 4.5, respectively. A 12-week trial of therapeutic oral anticoagulation was associated with a regression of mean transprosthetic pressure gradient and reversal of HALT. Follow-up 4D-MDCT corroborated thrombus resolution in both patients. Correspondingly, [18F]GP1 PET/CT imaging demonstrated decreased tracer uptake in both patients. Clot-to-blood ratio at follow-up visit decreased to 1.2 and 2.9, respectively. While absent tracer uptake was seen in patient #1, residual tracer uptake was observed in patient #2 suggestive of ongoing platelet aggregation. One asymptomatic SAVR patient was examined with [18F]GP1 PET/CT for a different compassionate use and no thrombotic foci were detected on the leaflets. Conclusions [18F]GP1 PET/CT is a novel imaging technique in patients with obstructive BPVT. In a head-to-head comparison we show that [18F]GP1 PET/CT may have incremental diagnostic value over dynamic contrast-enhanced 4D-MDCT alone by detection of sites of ongoing platelet aggregation at the molecular level. [18F]GP1 PET/CT may serve as a novel, highly sensitive tool to overcome some limitations of current diagnostic imaging modalities for detecting BPVT and may prove useful for the monitoring and guidance of therapeutic interventions. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Life Molecular Imaging provided material for [18F]GP1 radiolabeling free of charge as part of an ongoing research collaboration.

Background Severe tricuspid regurgitation (TR) is associated with high morbidity and mortality despite optimal medical treatment. Transcatheter tricuspid valve intervention (TTVI) is therefore emerging as a novel treatment option, fueling the hope to prolong survival and reduce rehospitalization for heart failure. Obviously, procedural success of TTVI is an important determinant of survival, but predictors for procedural success in patients treated with Cardioband system, which mimics the surgical approach by implanting an annular reduction system and hence targets tricuspid annulus dilatation as the central pathology in most patients, are largely elusive. Purpose This study aims to refine prediction of procedural success in patients with severe TR undergoing TTVI with Cardioband system by employing a random forest algorithm. Methods Procedural success was evaluated in 72 patients enrolled at two tertiary centers in Germany between 2018 and 2020. Key inclusion criterion was TR ≥ III/V° with high symptomatic burden despite optimal medical treatment. Procedural success war defined as patient alive at the end of the procedure, successful Cardioband implantation, and TR reduction ≥ II/V° as assessed on transthoracic echocardiography before discharge. Since 66.7% of patients were classified as “success”, a synthetic minority over-sampling technique was applied in order to train the random forest algorithm on a balanced data set. Results A random forest algorithm reached 85.4% accuracy (AUC: 0.923) in predicting procedural success in a balanced data set using eight parameters from pre-procedural echocardiography as input variables. Partial dependence analysis revealed that enlargement of the tricuspid valve (TV) anteroseptal diameter was most important for model accuracy. Applied to the real-world data set (24 patients classified as “failure” and 48 patients classified as “success”), the now trained random forest algorithm predicted procedural success with high sensitivity (70.8%) and specificity (100.0%), significantly outperforming the no information rate (p-value: 0.0069). Patients with low probability for success were characterized by impaired right ventricular function (TAPSE: 15.5±3.63 mm) and enlarged right sided cardiac diameters (basal right ventricular diameter: 51.6±3.79 mm; TV anteroseptal diameter: 45.0±5.10 mm). Notably, systolic pulmonary artery pressure (sPAP) and TV effective regurgitant orifice area were negatively correlated (R: −0.3004, p-value: 0.0322), and elevation in sPAP was attenuated in patients with low probability for procedural success (sPAP: 34.0±11.7 mmHg). Conclusion A random forest algorithm enables precise prediction of procedural success in patients treated with Cardioband system. TR reduction ≥ II/V° appears less achievable in patients with advanced stages of right heart failure, emphasizing the importance of adequate patient selection and timing of intervention. Funding Acknowledgement Type of funding sources: None.

Background Patients with isolated aortic valve stenosis (AS) at intermediate and even low-risk benefit from an interventional treatment with TAVI as compared to surgical aortic valve replacement. Whether patients with concomitant coronary artery disease have a better outcome with an interventional (PCI plus TAVI) or surgical (CABG plus SAVR) treatment strategy is still unclear. Purpose To evaluate the differences in 30-days (short-term) and one-year (intermediate term) mortality in women and men with CAD and AS undergoing a surgical or catheter-based treatment. Methods All patients were treated in Heart and Diabetes Center Bad Oeynhausen during 2016–2019. The surgical group contained 932 patients, the interventional cohort 360 patients as a result of setting a maximum time interval of 3 months between PCI and TAVR. CABG+SAVR and PCI+TAVR cohorts were compared by using a propensity score analysis including age, left ventricular function, EuroSCORE II and degree of CAD as matching parameters. After matching the total cohort, 406 patients could be obtained. The matched female cohort consisted of 114 patients, the matched male cohort of 284 patients. As a primary endpoint all-cause mortality was analyzed at 30 days and one year after the procedure. Furthermore, procedural and post-procedural outcome were analyzed. Results The studied TAVI cohort was a low to intermediate risk population (EuroScore II of the total cohort: 3.82 [2.49–6.64] in CABG+SAVR vs 4.36 [2.59–7.12] in PCI+TAVR, p=0.38; women: 6.18 [3.43–8.6], p=0.279; men: 4.39 [2.83–8.82], p=0.279). There was no significant difference in 30-days mortality between the surgical and interventional group, regarding the total cohort (3.9% vs 2.5%; p=0.398). Whereas in the male cohort 30-days mortality was comparable between interventional and surgical treatment (2.1% vs 2.1%; p=1), in the female group the surgical treatment showed a trend towards higher mortality without reaching statistical significance (8.8% vs 3.5%; p=0.242). Additionally, one-year mortality did not differ in the three cohorts between CABG+SAVR and PCI+TAVR (total cohort: 11.3% vs 12.8%; p=0.648 women: 14% vs 10.5%; p=0.568; men: 11.3% vs 14.8%; p=0.378). The number of postprocedural permanent pacemaker implantations was statistically higher after TAVR plus PCI (total cohort: 7.4% vs 15.3%; p=0.012; women: 7% vs 19.3%; p=0.052; men: 8.5% vs 19%; p=0.01). Furthermore, a significantly longer length of hospital stay was reported for the surgical cohort (total cohort: 13 [11–17] vs 11 [9–15]; p=0; women: 14 [12–18] vs 12 [10.5–15.5]; p=0.019; men: 13 [11–15] vs 11 [9–15]; p=0). Conclusion In patients with AS and CAD there is no significant difference in short and intermediate term mortality when comparing surgical or interventional treatment. Subsequently, an interventional approach might be a legitimate alternative to CABG+SAVR in these patients. Funding Acknowledgement Type of funding sources: None.

Background: Treatment options for secondary tricuspid regurgitation (TR) remain limited. Early real-world data of a new percutaneous direct annuloplasty system for tricuspid repair were examined. Methods: The first 60 patients treated with the Cardioband tricuspid valve repair system at 4 centers were included in this retrospective study. The primary efficacy end point was technical success with reduction of TR ≥2 grades at discharge. Combined primary safety end point was major adverse events (death, myocardial infarction, cardiothoracic surgery, and stroke) at 30 days. Results: Median patient age was 76 years (73–82), median EuroScore II was 3.9% (2.2–8.1), heart failure with preserved ejection fraction was present in 78%, and 81.7% were in the New York Heart Association class III/IV. Massive or torrential TR was found in 51.7%, and severe TR in 48.3%. The primary efficacy end point was achieved in 45%, while 60.3% of patients had less-than-severe TR at discharge. Vena contracta was reduced by 47% from 12.9±4.8 to 7.0±3.4 mm ( P P P =0.817) when comparing procedure numbers 11 or more to the earliest 5 procedures per center. Conclusions: This first real-world experience suggests that transcatheter treatment of advanced secondary TR using direct annuloplasty is feasible and reasonably safe early in the learning curve, with significant symptomatic benefit. Further studies are warranted to provide data on long-term outcome and patient prognosis.

We sought to unravel pathomechanisms of the transition of maladaptive right ventricular (RV) remodeling to right heart failure (RHF) upon pressure overload. Exposure of C57BL/6J and C57BL/6N mice to pulmonary artery banding disclosed a tight relation of structural remodeling with afterload, but a dissociation from RV systolic function. Reduced release of mitochondrial reactive oxygen species in C57BL/6J mice prevented the development of RHF. In patients with left heart failure, increased oxidative damage in RV sections was associated with severely impaired RV function. In conclusion, reactive oxygen species are involved in the transition of maladaptive RV remodeling to RHF.

Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.

Background Correct sizing of the aortic annulus and determination of coronary height is crucial for the efficacy and safety of trans-catheter aortic valve replacement (TAVR). We aimed to compare 3 different software solutions and manual measurements with respect to MDCT-derived annulus sizing parameters, reproducibility and processing time for TAVR planning and to evaluate the impact on patients' outcome. Methods One-hundred-seventeen patients with severe aortic stenosis prior to TAVR were included. Prosthesis sizes were determined separately using 3 different platforms: i) 3mensio, ii) IntelliSpacePortal V7 (ISP7), and iii) ISP9. In addition, manual measurements were performed. Intra- and inter-observer reproducibility as well as systematic differences were assessed. Finally, hypothetical prosthesis sizing was related to patient outcome using 3mensio as the clinical reference standard. Results Intra- and inter-observer reproducibility were excellent for all annulus parameters (ICCs 0.787–0.994). Distances to coronary ostia showed excellent intra-observer reproducibility except for 3mensio (ICC LCO: 0.655; RCO: 0.020), while inter-observer reproducibility was poor except for ISP9. For annulus parameters, slightly larger values were observed for ISP9 when compared to the other platforms. ISP9 allowed for the fastest and most reproducible measurement of aortic annulus parameters (although it did result in slightly larger annulus sizing). Conclusions Reproducible measurement of aortic annulus parameters can be obtained by all investigated post-processing solutions. All post-processing platforms are likely to result in similar and reliable measurements and thus can be used interchangeably.

Bleeding after cardiac surgery or cardiovascular interventions is associated with worse patient outcome. Only very limited data are available on the subject of bleeding after percutaneous edge-to-edge mitral valve repair (PMVR). We performed a single center analysis including 347 consecutive patients who underwent PMVR. Bleeding was defined according to the Mitral Valve Academic Research Consortium (MVARC) end point definition. The incidence of MVARC bleeding was 21.6% (n = 75), whereas major MVARC bleeding (hemoglobin decrease ≥3 g/dl) occurred in 7.4% (n = 26). Only 33.3% of all bleeding cases were access site-related. In multivariate regression analyses, independent predictors of MVARC bleeding were the presence of coronary artery disease (2.809, 95% CI 1.123 to 7.022, p = 0.027) and intervention duration (1.010, 95% CI 1.002 to 1.018, p = 0.010). Patients experiencing MVARC bleeding had longer hospital stays (p = 0.026); however, neither major nor extensive MVARC bleeding was associated with increased 30-day or 1-year mortality. A decrease in hemoglobin levels ≥3 g/dl without clinically visible bleeding sign-not considered in the MVARC bleeding definition-occurred in 9.5% of patients. A hemoglobin decrease of ≥4 g/dl had a strong association with worse survival in those patients with obscure bleeding. In conclusion, these data show a relevant incidence of bleeding after PMVR. In contrast to other cardiovascular interventions, the majority of bleedings were not access site-related. Particularly, patients with obscure bleeding, which are not included in the MVARC end point definitions, had worse outcomes and should therefore be considered for a more intensive workup.

Interventionelle Therapieverfahren besitzen bereits heute eine entscheidende Bedeutung in der Behandlung von Herzklappenerkrankungen vor allem bei Patienten mit bestehender Herzinsuffizienz. Insbesondere die Behandlung der Aortenklappenstenose wurde durch das TAVI-Verfahren in den letzten Jahren revolutioniert, so sollte bereits heute fur Patienten mit intermediarem und hohem perioperativen Risiko der kathetergestutzte transfemorale Aortenklappenersatz Therapie der ersten Wahl sein. Die Behandlung der Mitralklappeninsuffizienz mit dem MitraClip®-System fuhrt nachweislich bei Patienten mit hochgradig eingeschrankter linksventrikularer Funktion zur Verbesserung der Lebensqualitat sowie Reduktion Herzinsuffizienz-bedingter Symptome und Rehospitalisierungsraten. Auch Patienten mit besserer Ejektionsfraktion konnen von diesem Therapieansatz profitieren, wenn das Operationsrisiko aufgrund von Alter oder Komorbiditaten signifikant erhoht ist. Die kathetergestutzte Behandlung der Trikuspidalklappeninsuffizienz steht derzeit noch am Anfang ihrer Entwicklung – im Einzelfall haben jedoch bereits heute unterschiedliche Therapiestrategien einen Behandlungserfolg bei inoperablen Patienten nachweisen konnen, bei denen therapierefraktare Symptome einer fortgeschrittenen Rechtsherzinsuffizienz vorlagen. Die Entwicklung auf dem Gebiet der kathetergestutzten Herzklappentherapie hat sich in den letzten Jahren rasant vollzogen. Es ist davon auszugehen, dass durch anhaltenden Fortschritt und neue Studien in Zukunft noch weitere Patienten von diesen Therapieansatzen profitieren werden.

Objectives: We evaluated end-tidal CO2 (etCO2), which has been proposed to assess acute hemodynamic changes, to guide percutaneous edge-to-edge mitral valve repair (PMVR) with the MitraClip system. Methods: Thirty-nine patients (aged 78 ± 14 years) undergoing PMVR for moderate-to-severe mitral regurgitation (MR) of primary and secondary etiology were included. General anesthesia was maintained with sevoflurane and constant ventilation parameters to ensure stable etCO2 tension. MR grade was determined semiquantitatively by transesophageal echocardiography by 2 experienced operators blinded to etCO2 measurements. etCO2 levels were measured 3, 5, 10, and 15 min after final MitraClip placement. Results: Overall, etCO2 increased from 32.2 ± 1.7 before to 35.4 ± 3.0, 34.6 ± 2.6, and 34.2 ± 2.4 mm Hg 3, 5, and 10 min after implantation. A significant correlation was noted between the echocardiographic reduction in MR grade and the increase in etCO2. ANOVA for repeated measures confirmed a significant increase in etCO2 after clip implantation (corrected F = 20.0; p < 0.001) and revealed a significantly greater increase in etCO2 in patients with MR reduction ≥2 grades as compared to lesser MR reductions (F = 6.47; p = 0.015). Blood pressure changes did not correlate with the degree of MR reduction. Conclusions: We observed a close correlation between the reduction in MR grade during PMVR and etCO2, which might evolve as a useful parameter to complement treatment guidance during PMVR.

The aim of this study was to identify predictors of permanent pacemaker implantation (PPMI) following transcatheter aortic valve replacement (TAVR) with a balloon-expandable transcatheter valve (Edwards SAPIEN 3).New-onset conduction disturbances requiring PPMI remain a major concern following TAVR. Predictors are not yet well defined.The influence of angiographic implantation depth, device landing zone calcium volume, oversizing, pre- and post-dilation, and baseline conduction disturbances on PPMI rate was analyzed in 229 patients undergoing TAVR with the SAPIEN 3 device.PPMI was performed in 14.4% of patients. Patients requiring PPMI had higher left ventricular outflow tract (LVOT) calcium volume in the area below the left coronary cusp (LVOTLVOT

Pulmonary arterial hypertension (PAH) remains a disease with limited therapeutic options and dismal prognosis. Despite its etiologic heterogeneity, the underlying unifying pathophysiology is characterized by increased vascular tone and adverse remodeling of the pulmonary circulation. Myeloperoxidase (MPO), an enzyme abundantly expressed in neutrophils, has potent vasoconstrictive and profibrotic properties, thus qualifying as a potential contributor to this disease. Here, we sought to investigate whether MPO is causally linked to the pathophysiology of PAH. Investigation of 2 independent clinical cohorts revealed that MPO plasma levels were elevated in subjects with PAH and predicted adverse outcome. Experimental analyses showed that, upon hypoxia, right ventricular pressure was less increased in Mpo-/- than in WT mice. The hypoxia-induced activation of the Rho-kinase pathway, a critical subcellular signaling pathway yielding vasoconstriction and structural vascular remodeling, was blunted in Mpo-/- mice. Mice subjected to i.v. infusion of MPO revealed activation of Rho-kinase and increased right ventricular pressure, which was prevented by coinfusion of the Rho-kinase inhibitor Y-27632. In the Sugen5416/hypoxia rat model, PAH was attenuated by the MPO inhibitor AZM198. The current data demonstrate a tight mechanistic link between MPO, the activation of Rho-kinase, and adverse pulmonary vascular function, thus pointing toward a potentially novel avenue of treatment.

Background: Severe tricuspid regurgitation (TR) is associated with high morbidity and mortality rates with limited treatment options. We report the six-month safety and performance of the Cardioband™ Tricuspid Valve Reconstruction System in the treatment of severe functional TR in 30 patients enrolled in the TRI-REPAIR study. Methods: Between October 2016 and July 2017, 30 patients were enrolled in this single-arm, multicenter, prospective trial. Patients were diagnosed with severe, symptomatic TR in the absence of untreated left-heart disease and deemed inoperable because of unacceptable risk for open-heart surgery by the local heart team. Clinical, functional, and echocardiographic data were prospectively collected before and up to six months post-procedure. An independent core lab assessed all echocardiographic data and an independent Clinical Event Committee adjudicated the safety events. Findings: Mean patient age was 75 years and all patients presented with functional TR. At baseline, 25 (83%) patients were in NYHA Class III-IV and LVEF was 58%. Technical success was 100%. Through six months, three (10%) patients died. Between baseline and 6 months, echocardiography showed average reductions of annular septolateral diameter of 10% (41·9mm vs. 37·9mm; p=0·0014), PISA EROA of 48% (0·78cm2 vs. 0·41cm2, p=0·0004), and mean vena contracta of 28% (1·2cm vs. 0·9cm, p

Rationale: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. Objective: To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. Methods and Results: In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18 integrin–deficient (CD11b −/− ) mice and intravenous myeloperoxidase infusion revealed that neutrophil infiltration is a prerequisite for myocardial myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo −/− ) mice showed less pronounced slowing and decreased heterogeneity of electric conduction in the peri-infarct zone than wild-type mice. Expression of the redox-sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri-infarct area of wild-type compared with Mpo −/− mice. In isolated wild-type cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H 2 O 2 incubation. Mapping of induced pluripotent stem cell–derived cardiomyocyte networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase-dependent activation of matrix metalloproteinase 7. Moreover, Mpo −/− mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases resulting in upregulated collagen generation. In support of our experimental findings, baseline myeloperoxidase plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable cardioverter–defibrillator implantation in a cohort of 2622 stable patients with an ejection fraction >35% undergoing elective diagnostic cardiac evaluation. Conclusions: Myeloperoxidase emerges as a crucial mediator of postischemic myocardial remodeling and may evolve as a novel pharmacological target for secondary disease prevention after myocardial ischemia.

Background Platelet inhibition has been linked to improved endothelial function, a prognostic factor in coronary artery disease. Whether prasugrel, a potent platelet inhibitor, affects endothelial function remains unknown. Methods This was a double-blind, randomized, active-controlled, parallel trial. Patients with unstable angina pectoris undergoing percutaneous coronary intervention (PCI) received either a daily dose of clopidogrel 75mg (n=23) or prasugrel 10mg (n=22). Flow-mediated dilation (FMD), circulating nitrate and nitrite, inflammatory markers and platelet-leukocyte aggregates (PLAs) were assessed the day after PCI and after 3months. Results Baseline patient demographics were well matched between treatment groups. Prasugrel led to a significant improvement of FMD after 3months (9.01±3.64% vs. 6.65±3.24%, p=0.001). In contrast, no significant change was observed in the clopidogrel group (7.21±2.84% vs. 6.30±2.97%, p=0.187). Adjusted for baseline FMD, hyperlipidemia and statin use, the treatment effect on change in FMD favoured prasugrel by an absolute 1.97% (95% CI 0.29% to 3.66%, p=0.023). A significant reduction of plasma hsCRP, myeloperoxidase and neutrophil elastase and an increase of nitrate levels were noted in both treatment arms. Interestingly, only prasugrel significantly reduced sCD40 ligand and RANTES and increased nitrite levels. Prasugrel reduced the ADP-stimulated increase in PLAs by 40% (IR: 82 to 13), whereas clopidogrel revealed no such effect (1% increase (IR: 13 to 50) (p=0.01). Conclusion Prasugrel exhibits beneficial mid-term effects on endothelial nitric oxide bioavailability and inflammatory markers. (EudraCT number: 2009-015406-19).

We evaluated end-tidal CO2 (etCO2), which has been proposed to assess acute hemodynamic changes, to guide percutaneous edge-to-edge mitral valve repair (PMVR) with the MitraClip system.Thirty-nine patients (aged 78 ± 14 years) undergoing PMVR for moderate-to-severe mitral regurgitation (MR) of primary and secondary etiology were included. General anesthesia was maintained with sevoflurane and constant ventilation parameters to ensure stable etCO2 tension. MR grade was determined semiquantitatively by transesophageal echocardiography by 2 experienced operators blinded to etCO2 measurements. etCO2 levels were measured 3, 5, 10, and 15 min after final MitraClip placement.Overall, etCO2 increased from 32.2 ± 1.7 before to 35.4 ± 3.0, 34.6 ± 2.6, and 34.2 ± 2.4 mm Hg 3, 5, and 10 min after implantation. A significant correlation was noted between the echocardiographic reduction in MR grade and the increase in etCO2. ANOVA for repeated measures confirmed a significant increase in etCO2 after clip implantation (corrected F = 20.0; p0.001) and revealed a significantly greater increase in etCO2 in patients with MR reduction ≥2 grades as compared to lesser MR reductions (F = 6.47; p = 0.015). Blood pressure changes did not correlate with the degree of MR reduction.We observed a close correlation between the reduction in MR grade during PMVR and etCO2, which might evolve as a useful parameter to complement treatment guidance during PMVR.

Background: Current surgical and medical treatment options for severe tricuspid regurgitation (TR) are limited, and additional interventional approaches are required. In the present observational study, the safety and feasibility of transcatheter repair of chronic severe TR with the MitraClip system were evaluated. In addition, the effects on clinical symptoms were assessed. Methods: Patients with heart failure symptoms and severe TR on optimal medical treatment were treated with the MitraClip system. Safety, defined as periprocedural adverse events such as death, myocardial infarction, stroke, or cardiac tamponade, and feasibility, defined as successful implantation of 1 or more MitraClip devices and reduction of TR by at least 1 grade, were evaluated before discharge and after 30 days. In addition, functional outcome, defined as changes in New York Heart Assocation class and 6-minute walking distance, were assessed. Results: We included 64 consecutive patients (mean age 76.6±10 years) deemed unsuitable for surgery who underwent MitraClip treatment for chronic, severe TR for compassionate use. Functional TR was present in 88%; in addition, 22 patients were also treated with the MitraClip system for mitral regurgitation as a combined procedure. The degree of TR was severe or massive in 88% of patients before the procedure. The MitraClip device was successfully implanted in the tricuspid valve in 97% of the cases. After the procedure, TR was reduced by at least 1 grade in 91% of the patients, thereof 4% that were reduced from massive to severe. In 13% of patients, TR remained severe after the procedure. Significant reductions in effective regurgitant orifice area (0.9±0.3cm 2 versus 0.4±0.2cm 2 ; P P =0.001), and regurgitant volume (57.2±12.8 mL/beat versus 30.8±6.9 mL/beat; P P P =0.007). Conclusions: Transcatheter treatment of TR with the MitraClip system seems to be safe and feasible in this cohort of preselected patients. Initial efficacy analysis showed encouraging reduction of TR, which may potentially result in improved clinical outcomes.

Background Besides its well-established role in atherosclerosis, myeloperoxidase (MPO) has gained attention as a prognostic indicator in cardiovascular disease. Previous studies assessed MPO retrospectively and at a single time point. The current study aimed to evaluate the prognostic information of MPO prospectively and in consecutive measurements in patients presenting with chest pain. Methods MPO plasma levels were determined in 274 consecutive chest pain patients admitted to the emergency room. Results A total of 100 patients (36.5%) were finally diagnosed for acute myocardial infarction (AMI). Patients with AMI had significantly higher MPO levels than patients without AMI. Importantly, MPO levels were elevated in patients finally diagnosed for AMI even when troponin I (TNI) was negative (cutoff: 0.032ng/ml). Overall, MPO yielded a negative predictive value (NPV) of 85.5% (95% confidence interval (CI): 82.6–88.4) and a sensitivity for diagnosing AMI of 80.0% (95% CI: 75.8–84.2) compared to a NPV of 91.7% (95% CI: 89.5–94.0) and a sensitivity of 85.9% (95% CI: 82.3–89.5) for TNI. For patients with a symptom onset of ≤2h the sensitivity of MPO increased to 95.8% (95% CI: 93.7–97.9) whereas the sensitivity of TNI dropped to 50.0% (95% CI: 44.8–55.2). The negative predictive value of MPO for this group of patients was 95.6% (95% CI: 94.0–97.3) compared to 73.3% (95% CI: 69.8–76.9) for TNI. Discussion The current data underscore the role of MPO as diagnostic marker in acute coronary disease; however the additive information derived from MPO is restricted to patients presenting in the early phase of symptom onset.

Aims Observational studies have suggested a mechanistic link between the leucocyte-derived enzyme myeloperoxidase (MPO) and vasomotor function. Here, we tested whether MPO is systemically affecting vascular tone in humans. Methods and results A total of 12 135 patients were screened for leucocyte peroxidase activity. We identified 15 individuals with low MPO expression and activity (MPOlow), who were matched with 30 participants exhibiting normal MPO protein content and activity (control). Nicotine-dependent activation of leucocytes caused attenuation of endothelial nitric oxide (NO) bioavailability in the control group ( P < 0.01), but not in MPOlow individuals ( P = 0.12); here the MPO burden of leucocytes correlated with the degree of vasomotor dysfunction ( P = 0.008). To directly test the vasoactive properties of free circulating MPO, the enzyme was injected into the left atrium of anaesthetized, open-chest pigs. Myeloperoxidase plasma levels peaked within minutes and rapidly declined thereafter, reflecting vascular binding of MPO. Blood flow in the left anterior descending artery and the internal mammary artery (IMA) as well as myocardial perfusion decreased following MPO injection when compared with albumin-treated animals ( P < 0.001). Isolated IMA-rings from animals subjected to MPO revealed markedly diminished relaxation in response to acetylcholine ( P < 0.01) and nitroglycerine as opposed to controls ( P < 0.001). Conclusion Myeloperoxidase elicits profound effects on vascular tone of conductance and resistance vessels in vivo . These findings not only call for revisiting the biological functions of leucocytes as systemic and mobile effectors of vascular tone, but also identify MPO as a critical systemic regulator of vasomotion in humans and thus a potential therapeutic target.

Recruitment of polymorphonuclear neutrophils (PMNs) remains a paramount prerequisite in innate immune defense and a critical cofounder in inflammatory vascular disease. Neutrophil recruitment comprises a cascade of concerted events allowing for capture, adhesion and extravasation of the leukocyte. Whereas PMN rolling, binding, and diapedesis are well characterized, receptor-mediated processes, mechanisms attenuating the electrostatic repulsion between the negatively charged glycocalyx of leukocyte and endothelium remain poorly understood. We provide evidence for myeloperoxidase (MPO), an abundant PMN-derived heme protein, facilitating PMN recruitment by its positive surface charge. In vitro, MPO evoked highly directed PMN motility, which was solely dependent on electrostatic interactions with the leukocyte's surface. In vivo, PMN recruitment was shown to be MPO-dependent in a model of hepatic ischemia and reperfusion, upon intraportal delivery of MPO and in the cremaster muscle exposed to local inflammation or to intraarterial MPO application. Given MPO's affinity to both the endothelial and the leukocyte's surface, MPO evolves as a mediator of PMN recruitment because of its positive surface charge. This electrostatic MPO effect not only displays a so far unrecognized, catalysis-independent function of the enzyme, but also highlights a principal mechanism of PMN attraction driven by physical forces.

Activation of leukocytes, in particular polymorphonuclear neutrophils (PMN), is considered an early event in unstable coronary disease. Upon activation PMN liberate myeloperoxidase (MPO), an enzyme which binds to the vessel wall and depletes vascular NO bioavailability. Using coronary balloon angioplasty as a trigger to provoke coronary plaque injury, we assessed the time course of neutrophil activation, local and peripheral levels of myeloperoxidase, and systemic vascular NO bioavailability in patients with stable coronary artery disease. Twenty-four patients with stable CAD were enrolled prior to undergoing percutaneous interventions (PCI, n=14) and diagnostic coronary angiography (n=10), respectively. Following angioplasty arterial MPO plasma levels increased (231.5+/-67.6 to 273.8+/-80.4 pg/mg protein; P

Aim Atrial fibrosis, one of the most striking features in the pathology of atrial fibrillation (AF), is promoted by local and systemic inflammation. Electrophilic fatty acid nitroalkenes, endogenously generated by both metabolic and inflammatory reactions, are anti-inflammatory mediators that in synthetic form may be useful as drug candidates. Herein we investigate whether an exemplary nitro-fatty acid can limit atrial fibrosis and AF. Methods and results Wild-type C57BL6/J mice were treated for 2 weeks with angiotensin II (AngII) and vehicle or nitro-oleic acid (10-nitro-octadec-9-enoic acid, OA-NO2, 6 mg/kg body weight) via subcutaneous osmotic minipumps. OA-NO2 significantly inhibited atrial fibrosis and depressed vulnerability for AF during right atrial electrophysiological stimulation to levels observed for AngII-naive animals. Left atrial epicardial mapping studies demonstrated preservation of conduction homogeneity by OA-NO2. The protection from fibrotic remodelling was mediated by suppression of Smad2-dependent myofibroblast transdifferentiation and inhibition of Nox2-dependent atrial superoxide formation. Conclusion OA-NO2 potently inhibits atrial fibrosis and subsequent AF. Nitro-fatty acids and possibly other lipid electrophiles thus emerge as potential therapeutic agents for AF, either by increasing endogenous levels through dietary modulation or by administration as synthetic drugs.

Pulmonary arterial hypertension (PAH) is characterized by adverse remodeling of pulmonary arteries. Although the origin of the disease and its underlying pathophysiology remain incompletely understood, inflammation has been identified as a central mediator of disease progression. Oxidative inflammatory conditions support the formation of electrophilic fatty acid nitroalkene derivatives, which exert potent anti-inflammatory effects. The current study investigated the role of 10-nitro-oleic acid (OA-NO2) in modulating the pathophysiology of PAH in mice. Mice were kept for 28 days under normoxic or hypoxic conditions, and OA-NO2 was infused subcutaneously. Right ventricular systolic pressure (RVPsys) was determined, and right ventricular and lung tissue was analyzed. The effect of OA-NO2 on cultured pulmonary artery smooth muscle cells (PASMCs) and macrophages was also investigated. Changes in RVPsys revealed increased pulmonary hypertension in mice on hypoxia, which was significantly decreased by OA-NO2 administration. Right ventricular hypertrophy and fibrosis were also attenuated by OA-NO2 treatment. The infiltration of macrophages and the generation of reactive oxygen species were elevated in lung tissue of mice on hypoxia and were diminished by OA-NO2 treatment. Moreover, OA-NO2 decreased superoxide production of activated macrophages and PASMCs in vitro. Vascular structural remodeling was also limited by OA-NO2. In support of these findings, proliferation and activation of extracellular signal-regulated kinases 1/2 in cultured PASMCs was less pronounced on application of OA-NO2.Our results show that the oleic acid nitroalkene derivative OA-NO2 attenuates hypoxia-induced pulmonary hypertension in mice. Thus, OA-NO2 represents a potential therapeutic agent for the treatment of PAH.

Atrial fibrosis with enhanced turnover and deposition of matrix proteins leads to inhomogeneous atrial electrical conduction and gives rise to electrical reentry circuits resulting in atrial fibrillation. The multifactorial pathogenesis of atrial fibrosis involves resident cardiac cells as well as infiltrating leukocytes, both generating and sequestering matrix metalloproteinases (MMPs), a key enzyme family involved in fibrosis. A growing body of evidence points toward an important role of reactive oxygen species (ROS) in the release and activation of pro-MMPs and the stimulation of pro-fibrotic cascades. Myeloperoxidase (MPO), a bactericidal enzyme released from activated polymorphonuclear neutrophils (PMN) is not only associated with a variety of cardiovascular diseases, but has also been shown to be mechanistically linked to atrial fibrosis and fibrillation. MPO catalyzes the generation of reactive species like hypochlorous acid, which affect intracellular signaling cascades in various cells and advance activation of pro-MMPs and deposition of atrial collagen resulting in atrial arrhythmias. Thus, inflammatory mechanisms effectively promote atrial structural remodeling and importantly contribute to the initiation and perpetuation of atrial fibrillation.

The pathophysiology of atrial fibrillation (AF) remains incompletely understood, despite its prevalence and contributing role in stroke and heart failure. Whereas previous studies have focused on the electrophysiological characteristics of AF, recent reports shed light on structural remodeling of the atria as a prerequisite for AF. Recent evidence suggests that atrial fibrosis is linked not only to stimulation of myocytes and fibroblasts, but also to the activation state of leukocytes. Recruitment of leukocytes with the release of reactive oxygen species, cytokines and growth factors is followed by increased matrix deposition, which leads to adverse atrial remodeling and suggests that inflammatory pathways are a prerequisite for AF. Here we review current evidence demonstrating the interrelation between inflammation and AF.