BACKGROUND:In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted.STUDY DESIGN:The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke.CONCLUSIONS:The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

OBJECTIVES Both balloon-expandable and self-expanding transcatheter aortic valves are used for transcatheter aortic valve implantation (TAVI). We compared procedural and clinical outcome variables of Sapien 3 and Evolut R/Pro in an all-comers collective. METHODS In this single-center registry, patients were consecutively treated with the Sapien 3 from November 2014 to March 2017 (n = 129) and from April 2017 to December 2018 mainly (>95%) with the Evolut R/Pro (n = 124), due to a switch in the main TAVI supplier driven by hospital management. Data were retrospectively analyzed before and after the switch. RESULTS One-year follow-up data were available for 122 (94%) of the Sapien and 112 (90%) of the Evolut patients. Baseline characteristics were comparable (EuroSCORE: Sapien 21.8 ± 0.9% vs Evolut 22.5 ± 0.8%; P=.20). Evolut implantation was associated with a higher radiation dose (Sapien 35770 ± 2345 mGy•cm² vs Evolut 85072 ± 8202 mGy•cm²; P<.001), more postimplantation balloon dilations (Sapien 17.1% vs Evolut 37.1%; P<.001), but similar procedure time (Sapien 75.2 ± 3.8 min vs Evolut 74.6 ± 3 min; P=.30). In-hospital mortality (Sapien 3.1% vs Evolut 4.0%; P=.70), all-cause mortality (Sapien 13.2% vs Evolut 15.3%; P=.70), all-stroke rate (Sapien 1.5% vs Evolut 6.5%; P=.05), and pacemaker implantation rate (Sapien 13.2% vs Evolut 18.5%; P=.30) were similar at 1 year. Permanent pacemaker rate was numerically higher in the first 6 months with Evolut (<6 months 26.7% vs >6 months 16%; P=.62); furthermore, radiation dose and balloon dilations also suggest a learning curve with Evolut. CONCLUSIONS Switching from Sapien 3 to Evolut R/Pro was not associated with a difference regarding periprocedural or 1-year clinical outcomes.

AIMS:We sought to assess (1) clinical outcomes of second-generation cryoballoon (CB) ablation for persistent atrial fibrillation (AF), and (2) the association of baseline and procedural covariates with atrial arrhythmia recurrence (AAR) after ablation.METHODS:A total of 135 patients (63 ± 11 years, 96 men [71%]) with persistent AF underwent CB ablation at three experienced electrophysiology centers. Freedom from AAR was estimated with the Kaplan-Meier method. A Cox proportional-hazards model was used to estimate the effects of baseline and procedural covariates on the likelihood of AAR.RESULTS:Freedom from AAR at 6, 12, and 18 months was estimated at 91% (95% confidence interval [CI] 86%-96%), 75% (95% CI, 67%-83%), and 53% (95% CI, 43%-65%), respectively. The presence of an implantable cardiac device (Hazard ratio [HR] 3.09; 95% CI, 1.37-7.00; P = .007), a left atrial (LA) diameter > 50 mm (HR 1.69; 95% CI, 1.02-2.79; P = .043), and absence of antiarrhythmic drug (AAD) therapy before the ablation procedure (HR 3.12; 95% CI, 1.72-5.64; P < .001) were associated with AAR. A trend toward an increased risk of AAR was revealed for women (HR 1.73; 95% CI, 0.96-3.11; P = .069).CONCLUSIONS:CB ablation for persistent AF resulted in freedom from AAR about that reported for RF ablation. The presence of an implantable cardiac device, LA size, and absence of AAD therapy at baseline were associated with the risk of AAR.

Background: Second-generation cryoballoon (CB2)-based pulmonary vein isolation (PVI) has demonstrated encouraging results in the treatment of atrial fibrillation (AF). This study sought to assess data on the safety, efficacy and clinical success of CB2-based PVI in patients with heart failure (HF) and reduced ejection fraction (HFrEF). Methods and Results: CB2-based PVI was performed in 551 consecutive patients in 3 highly experienced EP centers. Patients with HF and LVEF <= 40% were included (HFrEF group, n=50/551, 9.1%). Data were compared with propensity score-matched patients without HF and preserved left ventricular EF (LVEF) (n=50, control group). The median LVEF was HFrEF: 37% (35, 40) and control: 55% (55, 55), P<0.0001. Major periprocedural complications were registered in 4/50 (8%, HFrEF group) and 3/50 (6%, control group), P=0.695. The 12-month freedom from AF recurrence was 73.1% (95% confidence interval (CI): 61-88, HFrEF group) and 72.6% (95% CI: 61-87, control group), P=0.25. NYHA class decreased from 2.4 +/- 0.8 (baseline) to 1.7 +/- 0.8 at 12-month follow-up (P<0.0001). LVEF improved from a median of 37% (35, 40) prior to ablation to a median of 55% (40, 55), P<0.0001. Conclusions: CB2-based PVI in patients with HFrEF appeared to be safe, was associated with comparable periprocedural complications and showed promising clinical success rates equal to those for patients with preserved LVEF. NYHA class and LVEF significantly improved at 12-month follow-up.

Background: Cryoballoon (CB)-based pulmonary vein isolation (PVI) is an established treatment modality for patients suffering from paroxysmal or persistent atrial fibrillation (AF). Recently, the novel fourth-generation cryoballoon (CB4) was introduced which mainly provides a 40% shorter distal tip as compared to the second-generation cryoballoon (CB2). This two-centre analysis sought to assess the primary efficacy of the 28 mm CB4 for PVI and the feasibility of real-time signal recordings from the PVs considering the time-to-isolation (TTI).Methods and results: Eighty-four patients with paroxysmal or short-standing persistent AF underwent CB4-based PVI at two different hospitals. Individual freeze-cycle duration was set at TTI + 120 seconds. No bonus freeze was applied. A total of 331 pulmonary veins (PVs) including five left common PVs were identified and all PVs were successfully isolated. Mean freeze-cycle duration was 165.7 ± 31.5 seconds. The mean minimal CB temperature was -45.6 ± 7.6 °C with a real-time PVI visualisation rate of 78% (67/84 (79.8%) RSPVs, 55/84 (65.5%) RIPVs, 67/79 (84.8%) LSPVs, 66/79 (83.5%) LIPVs and 2/5 (40%) LCPV). Transient phrenic nerve palsy occurred in 2/84 (2.4%) patients during cryo-application along the RSPV.Conclusions: The novel CB4 provides both, a high acute efficacy and a high rate of real time electrical PV-recordings, thus facilitating individual ablation strategies based on TTI.

Background: The prevalence of atrial fibrillation (AF) increases with age. Second-generation cryoballoon (CB2)based PVI has demonstrated encouraging clinical results in the treatment of paroxysmal (PAF) and persistent atrial fibrillation (PersAF). The objective of this study was to assess data on safety, efficacy and long-term clinical success of CB2-based pulmonary vein isolation (PVI) in patients =75 years of age. Methods: CB2-based PVI was performed in 104 patients =75 years of age (elderly group) and symptomatic AF (PersAF: n =44, 42.3%) in three highly experienced German EP centers. The data was compared to propensity score matched patients with age b75 years (n =104, control group; PersAF: n =45, 43.3%, p=0.956). Results: Themedian age of the elderly groupwas 77.5 [75, 80] yearswhile itwas 63 [52, 70] years of control group patients (p=0.0001). The median procedure time was 92.5 [75, 120] minutes (elderly group) and 100 [75, 120] (control group), p =0.124. Major complications were registered in 7/ 104 (6.7%) elderly patients and 7/ 104 (6.7%) control group patients (p =0.999). Clinical success in terms of freedom from AF recurrence after oneyear follow-up was 80% (95% CI: 72-88) and 82% (95% CI: 75-90) and after three-year follow-up 59% (95% CI: 47-74) and 49% (95% CI: 37 64) for the elderly group and the control group, respectively (p=0.7). Conclusions: CB2-based PVI in patients =75 years of age appears safe, is associated with low procedure times and shows promising clinical success rates equal to patients of the younger population. (c) 2018 Elsevier B. V. All rights reserved.

Aims:Second-generation cryoballoon (CB2) based pulmonary vein isolation (PVI) has emerged as an effective treatment option for symptomatic atrial fibrillation (AF). The current study sought to assess the impact of different ablation protocols on the incidence and characteristics of procedural complications in a large patient cohort.Methods and results:A total of 563 consecutive patients with symptomatic AF who underwent CB2-based ablation between July 2012 and January 2016, were assessed. Three different ablation protocols were applied and characterized by (#1) a bonus-freeze following PVI, (#2) no bonus-freeze after PVI, and (#3) a 'time-to-effect'-guided strategy. Major complications occurred in 30/563 patients (5.3%) with phrenic nerve palsy (PNP) as the most frequent complication occurring in 2.7% of the cases. The overall incidence of complications was significantly lower in patients treated with a 'time-to-effect' guided ablation strategy compared with the other ablation protocols (8.1% [17/211] (protocol #1+#2) vs. 3.7% [13/352] (protocol #3), respectively; P = 0.026). The 'time-to-effect' guided ablation protocol was associated with less applied freeze-cycles and shorter freeze-cycle durations. Additionally, shorter procedure times, radiation exposures and lower volumes of contrast medium needed were assessed for the 'time-to-effect' guided protocol as compared with the other ablation protocols.Conclusion:The overall incidence of complications was 5.3% in our analysis. The most frequent complication was PNP. The use of a time-to-effect guided ablation protocol was associated with a lower incidence of major complications compared with a bonus-freeze and no bonus-freeze protocol.

Background: In Cryo-PVI real-time observation of pulmonary vein isolation (TTI) by 1st generation spiral mapping catheter (SMC1) enables individual titration of cryoenergy application and thereby reduces procedure duration and fluoroscopy time.The 2nd generation spiral mapping catheter (SMC2) for cryoablation was designed in various diameters (15, 20, 25 mm).Whereas the 15mm and 20mm SMC2 has 8 electrodes, the 25mm SMC2 was designed with 10 electrodes.If these novel features of the 2nd generation spiral mapping catheter influence procedural characteristics of Cryo-PVI is unknown Purpose: To evaluate impact of SMC2 on procedure duration, fluoroscopy time and TTI Observation in patients during Cryo-PVI in comparison with the spiral mapping catheter of the 1st generation (SMC1).Methods and Results: In this prospective case-control trail 98 patients (age: 65.3 611.7 years, female: 44% paroxysmal AF: 62%, CHA2DS2-VASc-Score: 2.8 61.6) undergoing PVI with 2nd generation cryoballoon were included.In 57 patients (58%) the SMC1 was applied (SMC1 group), whereas 41 patients (42%) underwent Cryo-PVI using the SM2 (SMC2 group).Baseline characteristics did not differ significantly between both study groups.All PVs (386/386, 100%) were isolated successfully.Size of SMC2 was determined by the operator after PV angiography.SMC2 with 20 mm diameter was applied in 12 patients, whereas in SMC2 with 25 mm diameter was used in 29 patients.Compared to SMC1 the shaft of SMC2 is much softer which leads to decreased maneuverability in patients with difficult anatomies.However, this did not translate into increased procedure duration or fluoroscopy time.Mean procedure duration was 72.0 618.9min in the SMC1 group and 72.4 621.0min in the SMC2 group (p¼0.93).Also mean fluoroscopy time was statistically not different in both study groups (SMC1: 15.0 65.7 min; SM2: 16.4 67.3; p¼0.66).TTI observation rate in the SMC1 group was 70.8% (160/226), whereas TTI observation rate (83.1%; 133/160PV) was significantly higher in the SMC2 group (p¼0.015).We were able to determine the time-to-isolation in 46/55 LSPVs (84%) in the SM1 group in contrast to 31/37 LSPVs (84%) in the SM2 group (p¼0.79), in 32/55 (58%) LIPVs in the SM1 group versus 32/37 LIPVS (86%) in the SM2 group (p¼0.01), in 42/57 RSPVs (74%) in the SM1 group compared to 33/41 RSPVs (81%) in the SM2 group (p¼0.48) and in 35/57 RIPVs (61%) in the SM1 group versus 35/41 RIPVs (85%) in the SMC2 group (p¼0.01). Conclusion:The novel SMC2 has been designed as a true guidewire with the ability to obtain real time PV electrograms during cryoballoon PVI.Even though the softer shaft of SMC2 leads to decreased maneuverability in patients with difficult anatomies, this does not lead to increased procedure duration or fluoroscopy time.Moreover, the availability of an increased diameter (25mm) with 10 instead of 8 electrodes leads to significant increase in the time-to-isolation observation rate.

BACKGROUND Second-generation cryoballoon (CB2)-based pulmonary vein isolation (PVI) has demonstrated encouraging clinical results for the treatment of paroxysmal atrial fibrillation (AF) and persistent AF. However, rhythm follow-up after PVI is mainly based on Holter electrocardiography of limited duration. OBJECTIVE The purpose of this study was to assess the real AF burden following CB2-based PVI in patients with implanted cardiac devices. METHODS A total of 670 consecutive patients underwent CB2based PVI at 3 electrophysiology centers. In 66 patients (9.9%), an implantable cardiac device with continuous monitor function was independently implanted before the procedure (device group). This patient cohort was compared to propensity score-matched patients without cardiac devices (n = 66; control group). RESULTS A total of 254 of 258 PVs (98.4% 0 in the device group were successfully isolated using only CB2. Postprocedural device interrogation found no device or lead malfunction related to the procedure. Periprocedural complications were registered in 7 of 66 patients (11%) in the device group and in 6 of 66 patients (9%) in the control group (P = .770). Phrenic nerve palsy occurred in 6 of 66 patients (9%) in the device group) and in 2 of 66 patients (3%) in the control group) (P = .274). Clinical success in terms of freedom from AF recurrence after a 1-year follow-up period was 63.8% (95% confidence interval 53-77) in the device group and 77.3% (95% confidence interval 68-88) in the control group (P = .038). In the device group, AF/AT burden decreased from 41.8% +/- 35.0% before the procedure to 10.2% +/- 22.4% after 1 year (P < .0001). CONCLUSION CB2-PVI seems safe and feasible in patients with an implanted cardiac device. A significantly higher AF/AT burden was seen in patients with an implanted cardiac device compared to a control group.

BACKGROUND Second-generation cryoballoon (CB2)-based pulmonary vein isolation (PVI) has demonstrated encouraging clinical results in the treatment of paroxysmal (PAF) and persistent atrial fibrillation (PersAF). However, the CB2 features a maximal diameter of 28 mm, and its adaptability to anatomic variations of the pulmonary veins (PVs) might be challenging.OBJECTIVE The purpose of this study was to assess the acute efficacy, safety, and long-term clinical results of CB2-based PVI in patients with a left common pulmonary vein (LCPV).METHODS Six hundred seventy consecutive patients underwent CB2-based PVI in 3 electrophysiology centers. In 74 patients (11%), an LCPV was identified (LCPV group). The data were compared to those from matched patients (n = 74) with normal PV anatomy and comparable baseline characteristics (control group). An antral occlusion of the complete LCPV ostium was feasible in 50% of patients in the LCPV group. If an antral occlusion could not be obtained, a sequential isolation of the first superior and inferior branches was applied.RESULTS All 74 LCPVs were successfully isolated. A total of 64% patients (LCPV group) and 66% patients (control group) remained in sinus rhythm after mean follow-up of 1.9 +/- 0.9 years (P = .820). In 18 of 26 patients (69%) with atrial tachyarrhythmia recurrence, a repeat procedure using radiofrequency energy was performed, and a total of 56% LCPVs were found to be persistently isolated (control group: 61% of left-sided PVs, P = .801).CONCLUSION Patients with an LCPV undergoing CB2-based PVI demonstrate a high acute success rate. Comparable results with regard to clinical success and durability of PVI were shown when comparing patients of the LCPV group and the control group.

BACKGROUNDPulmonary vein isolation (PVI) using the 2nd-generation cryoballoon (CB2) for the treatment of atrial fibrillation (AF) has demonstrated encouraging acute and mid-term results. However, follow-up data on outcomes beyond 1 year are sparse. We investigated the 3-year outcome after PVI using the CB2.Methods and Results:100 patients with paroxysmal (PAF, 70/100 [70%] patients) or persistent AF (pAF, 30/100 [30%] patients) underwent CB2-based PVI in 2 experienced centers in Germany. Freeze-cycle duration was 240 s. After successful PVI a bonus freeze-cycle of the same duration was applied in the first 71 patients but was omitted in the following 29 patients. Phrenic nerve palsy occurred in 3 patients (3%); 2 patients were lost to follow-up. After a median follow-up of 38 (29-50) months, 59/98 (60.2%) patients remained in stable sinus rhythm (PAF: 48/70 (69%), pAF: 11/28 (39%) P=0.0084). In 32/39 (77%) patients with arrhythmia recurrence, a second ablation procedure using radiofrequency energy was conducted. Persistent PVI was noted in 76/125 (61%) PVs. After a mean of 1.37±0.6 procedures and a median follow-up of 35 (25-39) months, 77/98 (78.6%) patients remained in stable sinus rhythm (PAF: 56/70 (80%), pAF: 20/28 (71%), P=0.0276).CONCLUSIONSCB2-based PVI resulted in a 60.2% single-procedure and a 78.6% multiple-procedure success rate after 3 years. Repeat procedures demonstrated a high rate of durable PVI.

BACKGROUND GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non-vitamin K antagonist oral anticoagulant (NOAC), became available.OBJECTIVES This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1.METHODS During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients' baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics.RESULTS Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA(2)DS(2)-VASc [ Congestive heart failure, Hypertension, Age >= 75 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score >= 2; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment.CONCLUSIONS The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [ GLORIA-AF]; NCT01468701) (C) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Objectives: MitraClip (MC) implantation has become a widely accepted therapeutic option in the treatment of severe mitral regurgitation (MR) in patients unsuitable for surgery. N-terminal B-type natriuretic peptide (NT-proBNP), a biomarker released in the ventricular wall reflecting excessive mechanical stress, is routinely used as a prognostic variable in the setting of heart failure therapy. We sought to evaluate the impact of acute post-procedural changes in NT-proBNP on clinical outcome after successful MC therapy.

Objectives The aim of the study was to assess predictors of acute procedural failure in surgical high-risk patients undergoing MitraClip (Abbott Vascular, Abbott Park, Illinois) therapy.Background MitraClip implantation is a novel percutaneous option to treat significant mitral regurgitation (MR).Methods In 300 patients (75 +/- 9 years of age, 190 [63%] men), of whom 32 (10.7%) had been unsuccessfully treated (discharge MR grade of >2+), baseline clinical and echocardiographic variables were evaluated by exact logistic regression and classification tree analyses to assess their impact on acute procedural failure. Acute procedural failure was differentiated into aborted procedure (no MitraClip implanted; n = 11) and "clip failure" (inadequate MR reduction despite MitraClip implantation; n = 21).Results Multivariate logistic regression identified effective regurgitant orifice area (EROA), mitral valve orifice area (MVOA), and mean transmitral pressure gradient (TMPG) as independent predictors of overall acute procedural failure. Classification tree analysis revealed that an EROA > 70.8 mm(2) (n = 28) was associated with a high rate (25%) of clip failures, whereas the combination of an MVOA <= 3.0 cm(2) and a TMPG >= 4mmHg (n = 16) was associated with a high rate (37.5%) of aborted procedures. Failure rates of <= 10% were observed in all patients with an EROA <= 70.8 mm(2) and either an MVOA> 3.0 cm(2) (n 217) or an MVOA <= 3.0 cm(2) in concert with a TMPG <= 3mm Hg (n = 39). Multinomial logistic regression identified an EROA > 70.8 mm(2) and a TMPG >= 4 mm Hg as independently predictive of clip failure, but an MVOA <= 3.0 cm(2) and a TMPG >= 4 mm Hg as independently predictive of procedure abortion.Conclusions In surgical high-risk patients undergoing MitraClip therapy, a TMPG >= 4 mm Hg, an EROA >= 70.8 mm(2), and an MVOA <= 3.0 cm(2) carry an increased risk of procedural failure. (C) 2014 by the American College of Cardiology Foundation

Background: Total serum transforming growth factor-beta 1 (tsTGF-1) is increased in patients with Marfan syndrome (MFS), but it has not been assessed in thoracic aortic aneurysm and dissection (TAAD), Loeys-Dietz syndrome (LDS), and bicuspid aortic valve disease (BAVD).Hypothesis tsTGF-1 is increased in genetic aortic syndromes including TAAD, LDS, MFS, and BAVD.Methods: We measured tsTGF-1 and performed sequencing of the genes FBN1, TGFBR1, and TGFBR2 in 317 consecutive patients with suspected or known genetic aortic syndrome (167 men, 150 women; mean age 4314years). TAAD was diagnosed in 20, LDS in 20, MFS in 128, and BAVD in 30 patients, and genetic aortic syndrome was excluded in 119 patients.Results: Elevated tsTGF-1 levels were associated with causative gene mutations (P = 0.008), genetic aortic syndrome (P = 0.009), and sporadic occurrence of genetic aortic syndrome (P = 0.048), whereas only genetic aortic syndrome qualified as an independent predictor of tsTGF-1 (P = 0.001). The tsTGF-1 levels were elevated in FBN1 and NOTCH1 mutations vs patients without mutations (both P = 0.004), and in NOTCH1 mutations vs ACTA2/MYH11 mutations (P = 0.015). Similarly, tsTGF-1 levels were elevated in MFS (P = 0.003) and in BAVD (P = 0.006) vs patients without genetic aortic syndrome. In contrast to specific clinical features of MFS, FBN1 in-frame mutations (P = 0.019) were associated with increased tsTGF-1 levels.Conclusions: tsTGF-1 is elevated in the entire spectrum of genetic aortic syndromes. However, gradual differences in the increases of tsTGF-1 levels may mirror different degrees of alteration of tsTGF-1 signaling in different genetic aortic syndromes.

Objectives: To date, percutaneous mitral valve repair using the MitraClip system is the most widely used catheter-based strategy to treat mitral regurgitation (MR). We report clinical and functional outcome after MitraClip therapy in patients ineligible for surgery due to contraindications or excessive operative risk.

OBJECTIVE:Myeloperoxidase (MPO) has emerged as an important pathophysiological determinant of inflammatory vascular artery disease. It is appreciated that vessel immobilized, rather than circulating, MPO is critical for the progression of atherosclerotic lesions. The objective of this study was to investigate whether vessel-immobilized MPO is associated with the extent of coronary plaque burden. METHODS:MPO plasma levels were determined by ELISA before and after heparin-release of vessel-bound MPO, to study the relation between vascular MPO deposition and densitometrically assessed coronary plaque burden in 77 patients with stable coronary artery disease. RESULTS:Patients with a low increase in MPO plasma levels upon heparinization had a significantly smaller total plaque area and volume (12.1[IR:6.2-19.4]mm(2) vs. 19.8[IR:11.3-31.5]mm(2), p < 0.01; 27.8[IR:12.3-44.8]mm(3) vs. 55.2[IR:24.2-87.5]mm(3), p < 0.05). Multivariable linear regression revealed that ΔMPO was independently associated with plaque area, and that ΔMPO increased with the number of affected vessels. Selective sampling confirmed the predominant role of coronary MPO deposition. CONCLUSION:Our data demonstrate that heparin-induced mobilization of vessel-bound MPO is closely linked to coronary plaque burden and thus further corroborate the evidence for the intimate involvement of this enzyme in vascular pathophysiology, as well as the importance of inflammation in atherosclerosis.