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.
To reveal the role of myeloperoxidase for the development of ventricular arrhythmias.
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
O
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.
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.
The aim of this study was to assess the value of echocardiographic right ventricular (RV) and systolic pulmonary artery pressure (sPAP) assessment in predicting transcatheter tricuspid edge-to-edge ...valve repair (TTVR) outcome.
RV dysfunction and pulmonary hypertension are associated with poor prognosis and are systematically sought during tricuspid regurgitation evaluation. The value of echocardiographic assessment in predicting TTVR outcome is unknown.
Data were taken from the TriValve (Transcatheter Tricuspid Valve Therapies) registry, which includes patients undergoing TTVR at 14 European and North American centers. The primary outcome was 1-year survival free from hospitalization for heart failure, and secondary outcomes were 1-year survival and absence of hospital admission for heart failure at 1 year.
Overall, 249 patients underwent TTVR between June 2015 and 2018 (mean tricuspid annular plane systolic excursion TAPSE 15.8 ± 15.3 mm, mean sPAP 43.6 ± 16.0 mm Hg). Tricuspid regurgitation grade ≥3+ was found in 96.8% of patients at baseline and 29.4% at final follow-up; 95.6% were in New York Heart Association functional class III or IV initially, compared with 34.3% at follow-up (p < 0.05). Final New York Heart Association functional class did not differ among TAPSE and sPAP quartiles, even when both low TAPSE and high sPAP were present. Rates of 1-year survival and survival free from hospitalization for heart failure were 83.9% and 78.7%, respectively, without significant differences according to baseline echocardiographic RV characteristics (TAPSE, fractional area change, and end-diastolic area) and sPAP (p > 0.05 for all).
TTVR provides clinical improvement, with 1-year survival free from hospital readmission >75% in patients with severe tricuspid regurgitation. Conventional echocardiographic parameters used to assess RV function and sPAP did not predict clinical outcome after TTVR.
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BACKGROUND:Transcatheter mitral valve replacement (TMVR) may mature to become a therapeutic option for high-risk patients with severe mitral regurgitation (MR), particularly in patients at high or ...prohibitive surgical risk. MR patients with preexisting aortic valve prosthesis have been excluded from most TMVR trials because of the potential risks of left ventricular outflow tract obstruction or interaction between the TMVR anchoring mechanism and the aortic prosthesis. We describe the procedural and short-term outcomes of transapical TMVR with the Tiara valve in patients experiencing severe symptomatic MR with previous aortic valve replacement (AVR).
METHODS AND RESULTS:Twelve consecutive high surgical risk patients (11 men; mean age, 75±6 years) with aortic valve prosthesis and severe MR underwent TMVR with Tiara valve. Aortic valves were mechanical in 5 and biological in 7 patients, while 1 patient had previously undergone implantation of a transcatheter valve within a failed bioprosthetic surgical valve. Six patients (50%) had undergone redo surgical aortic valve replacement. Clinical characteristics of the group include prior mitral valve repair in 2, prior coronary bypass grafting surgery in 5, chronic atrial fibrillation in 7, renal failure in 9, and pacemaker/cardiac resynchronization device in 9 patients. Mean Society of Thoracic Surgery score and EuroSCORE II were 10.5±4.4 and 12.4±3.7, respectively. Mean baseline left ventricular ejection fraction was 35.5±5.3% (range, 30%–45%). The Tiara valve was implanted uneventfully in all patients. Device migration or left ventricular outflow tract obstruction was not observed. No patient required conversion to open heart surgery or periprocedural hemodynamic support. Procedural success was 100% with no death, MI, stroke, major bleeding, or access site complications at 30 days. MR was eliminated in all 12 patients immediately after implantation.
CONCLUSIONS:Transapical mitral valve replacement with the Tiara valve in high-risk patients with severe MR and aortic valve prostheses is technically feasible and can be performed safely.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectiveResidual paravalvular regurgitation (PVR) has been associated to adverse outcomes after transcatheter aortic valve replacement (TAVR). This study sought to evaluate the impact of device ...landing zone (DLZ) calcification on residual PVR after TAVR with different next-generation transcatheter heart valves.Methods642 patients underwent TAVR with a SAPIEN 3 (S3; n=292), ACURATE neo (NEO; n=166), Evolut R (ER; n=132) or Lotus (n=52). Extent, location and asymmetry of DLZ calcification were assessed from contrast-enhanced CT imaging and correlated to PVR at discharge.ResultsPVR was ≥moderate in 0.7% of S3 patients, 9.6% of NEO patients, 9.8% of ER patients and 0% of Lotus patients (p<0.001), and these differences remained after matching for total DLZ calcium volume. The amount of DLZ calcium was significantly related to the degree of PVR in patients treated with S3 (p=0.045), NEO (p=0.004) and ER (p<0.001), but not in Lotus patients (p=0.698). The incidence of PVR ≥moderate increased significantly over the tertiles of DLZ calcium volume (p=0.046). On multivariable analysis, calcification of the aortic valve cusps, LVOT calcification and the use of self-expanding transcatheter aortic valve implantation (TAVI) prostheses emerged as predictors of PVR.ConclusionsThe susceptibility to PVR depending on the amount of calcium was mainly observed in self-expanding TAVI prostheses. Thus, DLZ calcification is an important factor to be considered in prosthesis selection for each individual patient, keeping in mind the trade-off between PVR reduction, risk of new pacemaker implantation and unfavourable valve ha emodynamics.
We present a case of transcatheter valve-in-valve replacement performed because of structural valve deterioration of a subcoronary implanted stentless aortic bioprosthesis. A 23-mm self-expandable ...transcatheter heart valve (THV) with supraannular seating was chosen. The procedure was performed with the patient under conscious sedation. After anchoring and partial valve deployment, the patient experienced an acute onset of angina. The angiogram showed left main coronary artery obstruction. Prompt resheathing and retrieval of the THV was performed, and the procedure was aborted. Subsequently, an open-heart redo operation was performed by the use of a sutureless aortic bioprosthesis, with satisfactory hemodynamic and clinical results.
The balloon-expandable Sapien 3 (Edwards Lifesciences, Irvine, CA, USA) and the mechanically-expandable Lotus valve (Boston Scientific, Marlborough, MA, USA) are established devices for transcatheter ...aortic valve implantation. We sought to compare both transcatheter heart valves (THV) under consideration of the extent of THV landing zone calcification.
This retrospective analysis includes consecutive patients with severe aortic stenosis treated with Sapien 3 (S3; n=212) or Lotus (n=61) THV via transfemoral access. Outcome was assessed according to VARC II definitions. Rate of paravalvular leakage (PVL), periprocedural stroke, and permanent pacemaker implantation (PPI) was adjusted for THV landing zone calcification as calculated by multi-slice computed tomography.
There was no difference in preoperative risk (all results as follows S3 vs. Lotus: STS-PROM 5.9±5.6% vs. 4.8±2.6%, p=0.14), rate of device success (95.3% vs. 95.1%, p=0.67), 30-day mortality (1.9% vs. 4.9%, p=0.16), periprocedural stroke (1.4% vs. 4.9%, p=0.27), and major access site complications (9.4% vs. 9.8%, p=0.93). PPI was more frequent (19.4% vs. 34.4%, p=0.01) and significant PVL was less frequent (≥mild PVL: 17.6% vs. 3.7%, p=0.04) after Lotus implantation. No association was found between landing zone calcification and periprocedural stroke rate (OR 1.19, 95%CI 0.92–1.54, p=0.17) or need for PPI (OR 1.04, 95%CI 0.91–1.18, p=0.57). The extent of landing zone calcification was associated with risk for PVL ≥mild (OR 1.21, 95%CI 1.03–1.42, p=0.02). After adjusting for landing zone calcification risk for PVL ≥mild was lower with the Lotus valve (OR 0.15, 95%CI 0.02–0.54, p=0.01).
Both THVs yield comparable procedural and clinical outcomes except for a higher PPI rate with the Lotus valve, which is independent from the extent of landing zone calcification. The extent of landing zone calcification is associated with an increased risk for PVL for both THV, but is significantly reduced with the Lotus valve.
A large, prospective international registry was developed to evaluate the initial clinical applications of transcatheter tricuspid valve intervention (TTVI) with different devices.
TTVI for native ...tricuspid valve dysfunction has been emerging during the last few years as an alternative therapeutic option to serve a large high-risk population of patients with severe symptomatic tricuspid regurgitation (TR).
The TriValve Registry included 312 high-risk patients with severe TR (76.4 ± 8.5 years of age; 57% female; EuroSCORE II 9 ± 8%) at 18 centers. Interventions included repair at the level of the leaflets (MitraClip, Abbott Vascular, Santa Clara, California; PASCAL Edwards Lifesciences, Irvine, California), annulus (Cardioband, Edwards Lifesciences; TriCinch, 4tech, Galway, Ireland; Trialign, Mitraling, Tewksbury, Massachusetts), or coaptation (FORMA, Edwards Lifesciences) and replacement (Caval Implants, NaviGate, NaviGate Cardiac Structures, Lake Forest, California). Clinical outcomes were prospectively determined during mid-term follow-up.
A total of 108 patients (34.6%) had prior left heart valve intervention (84 surgical and 24 transcatheter, respectively). TR etiology was functional in 93%, and mean annular diameter was 46.9 ± 9 mm. In 75% of patients the regurgitant jet was central (vena contracta 1.1 ± 0.5; effective regurgitant orifice area 0.78 ± 0.6 cm2). Pre-procedural systolic pulmonary artery pressure was 41 ± 14.8 mm Hg. Implanted devices included: MitraClip in 210 cases, Trialign in 18 cases, TriCinch first generation in 14 cases, caval valve implantation in 30 cases, FORMA in 24 cases, Cardioband in 13 cases, NaviGate in 6 cases, and PASCAL in 1. In 64% of the cases, TTVI was performed as a stand-alone procedure. Procedural success (defined as the device successfully implanted and residual TR ≤2+) was 72.8%. Greater coaptation depth (odds ratio: 24.1; p = 0.002) was an independent predictor of reduced device success. Thirty-day mortality was 3.6% and was significantly lower among patients with procedural success (1.9% vs. 6.9%; p = 0.04); Actuarial survival at 1.5 years was 82.8 ± 4% and was significantly higher among patients who had procedural success achieved.
TTVI is feasible with different technologies, has a reasonable overall procedural success rate, and is associated with low mortality and significant clinical improvement. Mid-term survival is favorable in this high-risk population. Greater coaptation depth is associated with reduced procedural success, which is an independent predictor of mortality.
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