Florian Deuschl

Comparison of vascular closure devices for access site closure after transfemoral aortic valve implantation

BACKGROUND The majority of transcatheter aortic valve implantation (TAVI) procedures are currently performed by percutaneous transfemoral approach. The potential contribution of the type of vascular closure device to the incidence of vascular complications is not clear. AIM To compare the efficacy of a Prostar XL- vs. Perclose ProGlide-based vascular closure strategy. METHODS The ClOsure device iN TRansfemoral aOrtic vaLve implantation (CONTROL) multi-center study included 3138 consecutive percutaneous transfemoral TAVI patients, categorized according to vascular closure strategy: Prostar XL- (Prostar group) vs. Perclose ProGlide-based vascular closure strategy (ProGlide group). Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. RESULTS Propensity matching identified 944 well-matched patients (472 patient pairs). Composite primary end point of major vascular complications or in-hospital mortality occurred more frequently in Prostar group when compared with ProGlide group (9.5 vs. 5.1%, P = 0.016), and was driven by higher rates of major vascular complication (7.4 vs. 1.9%, P < 0.001) in the Prostar group. However, in-hospital mortality was similar between groups (4.9 vs. 3.5%, P = 0.2). Femoral artery stenosis occurred less frequently in the Prostar group (3.4 vs. 0.5%, P = 0.004), but overall, Prostar use was associated with higher rates of major bleeding (16.7 vs. 3.2%, P < 0.001), acute kidney injury (17.6 vs. 4.4%, P < 0.001) and with longer hospital stay (median 6 vs. 5 days, P = 0.007). CONCLUSIONS Prostar XL-based vascular closure in transfemoral TAVI procedures is associated with higher major vascular complication rates when compared with ProGlide; however, in-hospital mortality is similar with both devices.

Induction of Atrial Fibrillation by Neutrophils Critically Depends on CD11b/CD18 Integrins

Background Recent observational clinical and ex-vivo studies suggest that inflammation and in particular leukocyte activation predisposes to atrial fibrillation (AF). However, whether local binding and extravasation of leukocytes into atrial myocardium is an essential prerequisite for the initiation and propagation of AF remains elusive. Here we investigated the role of atrial CD11b/CD18 mediated infiltration of polymorphonuclear neutrophils (PMN) for the susceptibility to AF. Methods and Results C57bl/6J wildtype (WT) and CD11b/CD18 knock-out (CD11b−/−) mice were treated for 14 days with subcutaneous infusion of angiotensin II (Ang II), a known stimulus for PMN activation. Atria of Ang II-treated WT mice were characterized by increased PMN infiltration assessed in immunohistochemically stained sections. In contrast, atrial sections of CD11b−/− mice lacked a significant increase in PMN infiltration upon Ang II infusion. PMN infiltration was accompanied by profoundly enhanced atrial fibrosis in Ang II treated WT as compared to CD11b−/− mice. Upon in-vivo electrophysiological investigation, Ang II treatment significantly elevated the susceptibility for AF in WT mice if compared to vehicle treated animals given an increased number and increased duration of AF episodes. In contrast, animals deficient of CD11b/CD18 were entirely protected from AF induction. Likewise, epicardial activation mapping revealed decreased electrical conduction velocity in atria of Ang II treated WT mice, which was preserved in CD11b−/− mice. In addition, atrial PMN infiltration was enhanced in atrial appendage sections of patients with persistent AF as compared to patients without AF. Conclusions The current data critically link CD11b-integrin mediated atrial PMN infiltration to the formation of fibrosis, which promotes the initiation and propagation of AF. These findings not only reveal a mechanistic role of leukocytes in AF but also point towards a potential novel avenue of treatment in AF.

Improving outcomes: case-matched comparison of novel second-generation versus first-generation self-expandable transcatheter heart valves

OBJECTIVES The published literature has extensively documented clinical benefit derived from transcatheter aortic valve implantation (TAVI) in high-risk patients using self-expanding current-generation transfemoral (TF) transcatheter heart valves (THVs). However, it has also demonstrated apparent shortcomings such as paravalvular leakage (PVL) or need for permanent pacemaker (PM) implantation. We here present a case-matched analysis of acute 30-day outcomes using a novel nitinol-based THV (Symetis Acurate Neo TF™), which may overcome some limitations of currently used devices. METHODS From 2012 to 2015, 69 consecutive patients (study group, 65.2% female, 81.4 ± 6.1 years, logEuroSCORE I 19.9 ± 14.2%) received TF-TAVI using the novel Symetis Acurate Neo TF™ THV. A control group of patients after TF-TAVI with the CoreValve™ THV was retrieved from our database (control group) and matched to the study group utilizing 16 parameters. Data were retrospectively analysed according to updated Valve Academic Research Consortium (VARC-2) definitions. The 30-day follow-up was completed in all cases. RESULTS Apart from gender (65.2 vs 44.9% females, P = 0.023), matching was successful with parameters showing no significant differences. The device success rate was 95.6% (66/69) and 89.9% (62/69) in the study and control groups, respectively (P = 0.20). The all-cause 30-day mortality rate was 5.8% (4/69) vs 10.14% (7/69) (P = 0.36), and disabling stroke was observed in 2.9% (2/69) vs 5.8% (4/69) (P = 0.41), respectively. Resultant transvalvular maximum/mean gradient and effective orifice area (EOA) were 13.8 ± 5.5 vs 18.1 ± 8.1 mmHg (P = 0.001)/7.0 ± 2.8 vs 8.8 ± 4.0 mmHg (P = 0.006) and 1.9 ± 0.3 vs 1.8 ± 0.2 cm(2) (P = 0.015), respectively. PVL ≥grade II was observed in 2.9% (2/69) and 15.94% (11/69) (P = 0.013) of patients and the rate of PM implantation was 8.7% (6/69) vs 44.9% (31/69) (P < 0.001), respectively. DISCUSSION TF-TAVI was feasible and safe using this new type of nitinol-based THV. Superiority to the current generation of self-expanding THVs was achieved regarding post-interventional pressure gradients and EOA, severity of residual PVL and rate of PM implantation. Results set a promising quality standard for TF-TAVI with a self-expanding THV, but will have to be confirmed in a larger patient cohorts for further clinical evaluation.

Compassionate use of the PASCAL transcatheter mitral valve repair system for patients with severe mitral regurgitation: a multicentre, prospective, observational, first-in-man study

BACKGROUND Severe mitral regurgitation is associated with impaired prognosis if left untreated. Using the devices currently available, transcatheter mitral valve repair (TMVr) remains challenging in complex anatomical situations. We report the procedural and 30-day results of the first-in-man study of the Edwards PASCAL TMVr system. METHODS In this multicentre, prospective, observational, first-in-man study, we collected data from seven tertiary care hospitals in five countries that had a compassionate use programme in which patients underwent transcatheter mitral valve repair using the Edwards PASCAL TMVr system. Eligible patients were those with symptomatic, severe functional, degenerative, or mixed mitral regurgitation deemed at high risk or inoperable. Safety and efficacy of the procedure were prospectively assessed at device implantation, discharge, and 30 days after device implantation. The key study endpoints were technical success assessed at the end of the procedure and device success 30 days after implantation using the Mitral Valve Academic Research Consortium definitions. FINDINGS Between Sept 1, 2016, and March 31, 2017, 23 patients (median age 75 years [IQR 61-82]) had treatment for moderate-to-severe (grade 3+) or severe (grade 4+) mitral regurgitation using the Edwards PASCAL TMVr system. At baseline, the median EuroScore II score was 7·1% (IQR 3·6-12·8) and the median Society of Thoracic Surgeons predicted risk of mortality for mitral valve repair was 4·8% (2·1-9·0) and 6·8% (2·9-10·1) for mitral valve replacement. 22 (96%) of 23 patients were New York Heart Association (NYHA) class III or IV at baseline. The implantation of at least one device was successful in all patients, resulting in procedural residual mitral regurgitation of grade 2+ or less in 22 (96%) patients. Six (26%) of 23 patients had two implants. Periprocedural complications occurred in two (9%) of 23 patients (one minor bleeding event and one transient ischaemic attack). Despite the anatomical complexity of mitral regurgitation in the patients in this compassionate use cohort, technical success was achieved in 22 (96%) of 23 patients, and device success at 30 days was achieved in 18 (78%) patients. Three patients (13%) died during the 30 day follow-up. 19 (95%) of 20 patients alive 30 days after implantation were NYHA class I or II. INTERPRETATION This study establishes feasibility of the Edwards PASCAL TMVr system with a high rate of technical success and reduction of mitral regurgitation severity. Further research is needed on procedural and long-term clinical outcomes. FUNDING None.

Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling

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/H2O2 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.

Transcatheter Mitral Valve Repair in Surgical High-Risk Patients: Gender-Specific Acute and Long-Term Outcomes

Background. Analyses emphasizing gender-related differences in acute and long-term outcomes following MitraClip therapy for significant mitral regurgitation (MR) are rare. Methods. 592 consecutive patients (75 ± 8.7 years, 362 men, 230 women) underwent clinical and echocardiographic follow-up for a median of 2.13 (0.99–4.02) years. Results. Significantly higher prevalence of cardiovascular comorbidities, renal failure, and adverse echocardiographic parameters in men resulted in longer device time (p = 0.007) and higher numbers of implanted clips (p = 0.0075), with equal procedural success (p = 1.0). Rehospitalization for heart failure did not differ (p[logrank] = 0.288) while survival was higher in women (p[logrank] = 0.0317). Logarithmic increase of NT-proBNP was a common independent predictor of death. Hypercholesterolemia and peripheral artery disease were predictors of death only in men while ischemic and dilative cardiomyopathy (CM) and age were predictors in women. Independent predictors of rehospitalization for heart failure were severely reduced ejection fraction and success in men while both ischemic and dilative CM, logistic EuroSCORE, and MR severity were predictive in women. Conclusions. Higher numbers of implanted clips and longer device time are likely related to more comorbidities in men. Procedural success and acute and mid-term clinical outcomes were equal. Superior survival for women in long-term analysis is presumably attributable to a comparatively better preprocedural health.

Critical evaluation of the MitraClip system in the management of mitral regurgitation

The MitraClip (MC) system is a device for percutaneous, transseptal edge-to-edge reconstruction of the mitral valve (MV) in patients with severe mitral regurgitation (MR) not eligible for surgery. Recently, a number of studies have underlined the therapeutic benefit of the MC system for patients with extreme and high risk for MV surgery suffering from either degenerative or functional MR. The MC procedure shows negligible intraprocedural mortality, low periprocedural complication rates, and a significant reduction in MR, as well as an improvement in functional capacity and most importantly quality of life. Presently, the MC system has become an additional interventional tool in the concert of surgical methods. It hereby enlarges the spectrum of MV repair for the Heart Team. Lately, many reviews focused on the MC system. The current review describes the developments in the treatment of MR with the MC system.

Direct percutaneous transaxillary implantation of a novel self-expandable transcatheter heart valve for aortic stenosis

The aim of this study was to evaluate safety, feasibility, and efficacy of transaxillary TAVI using a novel self‐expandable transcatheter heart valve (THV) via a direct percutaneous technique.

First-in-man treatment of a degenerated mitral surgical valve with the mechanical expanding Lotus™ valve

Percutaneous placement of transcatheter heart valves for treatment of degenerated surgical valves in the aortic and mitral position is an emerging therapy for selected high-risk patients. Here we describe in detail the first case in the literature of a patient (female, 72 years old, log EuroSCORE 22.9%) with a degenerated biological mitral prosthesis which was successfully treated by transapical implantation of a Lotus valve. The case described demonstrates the very controlled feasibility of valve-in-valve treatment for a degenerated mitral bioprosthesis with a mechanically expanding Lotus valve.

First in human implantation of the mechanical expanding Lotus® valve in degenerated surgical valves in mitral position

Implantation of transcatheter heart valves (THV) into degenerated surgical valves is an emerging therapy for selected high‐risk patients. Although, CE mark of most THV is limited for native aortic valvular stenosis, transcatheter valve implantation into degenerated bioprostheses, even in mitral position is very intriguing.