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1.
PLoS One ; 15(3): e0228913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126091

RESUMO

BACKGROUND: Mutations in the human desmin gene (DES) cause autosomal-dominant and -recessive cardiomyopathies, leading to heart failure, arrhythmias, and AV blocks. We analyzed the effects of vascular pressure overload in a patient-mimicking p.R349P desmin knock-in mouse model that harbors the orthologue of the frequent human DES missense mutation p.R350P. METHODS AND RESULTS: Transverse aortic constriction (TAC) was performed on heterozygous (HET) DES-p.R349P mice and wild-type (WT) littermates. Echocardiography demonstrated reduced left ventricular ejection fraction in HET-TAC (WT-sham: 69.5 ± 2.9%, HET-sham: 64.5 ± 4.7%, WT-TAC: 63.5 ± 4.9%, HET-TAC: 55.7 ± 5.4%; p<0.01). Cardiac output was significantly reduced in HET-TAC (WT sham: 13088 ± 2385 µl/min, HET sham: 10391 ± 1349µl/min, WT-TAC: 8097 ± 1903µl/min, HET-TAC: 5793 ± 2517µl/min; p<0.01). Incidence and duration of AV blocks as well as the probability to induce ventricular tachycardias was highest in HET-TAC. We observed reduced mtDNA copy numbers in HET-TAC (WT-sham: 12546 ± 406, HET-sham: 13526 ± 781, WT-TAC: 11155 ± 3315, HET-TAC: 8649 ± 1582; p = 0.025), but no mtDNA deletions. The activity of respiratory chain complexes I and IV showed the greatest reductions in HET-TAC. CONCLUSION: Pressure overload in HET mice aggravated the clinical phenotype of cardiomyopathy and resulted in mitochondrial dysfunction. Preventive avoidance of pressure overload/arterial hypertension in desminopathy patients might represent a crucial therapeutic measure.

3.
JACC Cardiovasc Interv ; 13(6): 751-761, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32192695

RESUMO

OBJECTIVES: The aim of this study was to determine the safety and efficacy of chimney stenting, a bailout technique to treat coronary artery occlusion (CAO). BACKGROUND: CAO during transcatheter aortic valve replacement (TAVR) is a rare but often fatal complication. METHODS: In the international Chimney Registry, patient and procedural characteristics and data on outcomes are retrospectively collected from patients who underwent chimney stenting during TAVR. RESULTS: To date, 16 centers have contributed 60 cases among 12,800 TAVR procedures (0.5%). Chimney stenting was performed for 2 reasons: 1) due to the development of an established CAO (n = 25 [41.6%]); or 2) due to an impending CAO (n = 35 [58.3%]). The majority of cases (92.9%) had 1 or more classical risk factors for CAO. Upfront coronary protection was performed in 44 patients (73.3%). Procedural and in-hospital mortality occurred in 1 and 2 patients, respectively. Myocardial infarction (52.0% vs. 0.0%; p < 0.01), cardiogenic shock (52.0% vs. 2.9%; p < 0.01), and resuscitation (44.0% vs. 2.9%; p < 0.01) all occurred more frequently in patients with established CAO compared with those with impending CAO. The absence of upfront coronary protection was the sole independent risk factor for the combined endpoint of death, cardiogenic shock, or myocardial infarction. During a median follow-up time of 612 days (interquartile range: 405 to 842 days), 2 cases of stent failure were reported (1 in-stent restenosis, 1 possible late stent thrombosis) after 157 and 374 days. CONCLUSIONS: Chimney stenting appears to be an acceptable bailout technique for CAO, with higher event rates among those with established CAO and among those without upfront coronary protection.

4.
Int Heart J ; 61(2): 364-372, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32132319

RESUMO

Atherosclerosis is a chronic inflammatory disease with multiple characteristic facets, including vascular inflammation, endothelial dysfunction, plaque development, impaired blood flow, and cholesterol deposition through dyslipidemia. Toll-like receptors (TLRs) of the innate immune system have been closely linked to the development of atherosclerotic lesions. TLR7 recognizes viral or endogenous single-stranded RNA, which is released during vascular apoptosis and necrosis. The role of TLR7 in vascular disease remains controversial, and therefore, we sought to investigate the effects of TLR7 stimulation in mice.Intravenous injection of a ligand for TLR7 (R848) induced a significant pro-inflammatory cytokine response in mice. This was associated with impaired reendothelialization upon acute denudation of the carotid artery, as measured by Evan's blue staining, and increased numbers of circulating endothelial microparticles (EMPs) and circulating Sca1/Flk1 positive cells as a marker for increased endothelial damage. Chronic subcutaneous stimulation of TLR7 in apolipoprotein E-deficient (ApoE-/-) mice increased aortic production of reactive oxygen species (ROS), the number of circulating EMPs, and most importantly, augmented the formation of atherosclerotic plaque when compared with vehicle-treated animals.Systemic stimulation of TLR7 leads to impaired reendothelialization upon acute vascular injury and is associated with the production of pro-inflammatory cytokines and increased levels of circulating EMPs and Sca1/Flk1 positive cells. Importantly, ApoE-/- mice chronically treated with R848 displayed increased atherosclerotic plaque development and elevated levels of ROS in the aortic tissue. In addition, TLR7-activation-induced apoptosis and impaired migration in human coronary artery endothelial cells and showed significant upregulation of the signaling cascade of IL-1 receptor-associated kinase (IRAK) 2 and IRAK4. Our data highlight the importance of fully understanding the pathomechanisms involved in atherogenesis, and further studies are necessary to identify the ligand-specific effects of TLR7 for possible therapeutic targeting.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32198810

RESUMO

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative treatment option to surgical aortic valve replacement (SAVR) in selected high-risk patients. In this study, we aimed to evaluate the prognostic value of right ventricular (RV) functional imaging to predict clinical response to TAVR and SAVR. METHODS: One hundred and ten patients with symptomatic severe aortic valve stenosis (AVS) undergoing successful TAVR and 32 controls undergoing SAVR were prospectively enrolled. Six months follow up (FU) included two-dimensional (2D) transthoracic echocardiography (TTE) with RV deformation imaging. RESULTS: Baseline TTE showed no significant differences between groups (TAVR and SAVR) in conventional left ventricular (LV) and RV functional parameters (LV ejection fraction [LV-EF]: p = .21; tricuspidal annular plane systolic excursion [TAPSE]: 1.8 ± 0.5 cm, 1.9 ± 0.4 cm, p = .21), and RV strain (right ventricular-global longitudinal strain [RV-GLS] -11.6 ± 5.2%, -11.5 ± 6.5%, p = .70). At FU LV function was unchanged in both groups (p > .05); RV function was significantly improved after TAVR (RV-GLS: -11.6 ± 5.2%, -13.4 ± 6.1%, p = .005; TAPSE: 1.8 ± 0.5 cm, 1.9 ± 0.3 cm, p = .05), and worsened after SAVR (RV-GLS: -11.5 ± 6.5%, -8.9 ± 5.2%, p = .04; TAPSE: 1.9 ± 0.4 cm, 1.5 ± 0.3 cm, p < .001). Functional New York Heart Association (NYHA) class remained unchanged in patients after SAVR (p = .21), and improved after TAVR (p < .001). Baseline RV function was linked with clinical response to TAVR (TAPSE, p < .0001; RV-GLS, p = .04), and the development of RV-GLS was associated with functional worsening after SAVR (p = .05). CONCLUSION: Baseline RV function and changes of right heart mechanics are closely associated with functional improvements after AVR. SAVR, but not TAVR, seems to have detrimental effects on RV-function.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32190961

RESUMO

BACKGROUND: In the continuity equation, assumption of a round-shaped left ventricular outflow tract (LVOT) leads to underestimation of the true aortic valve area in two-dimensional echocardiography. The current study evaluated whether inclusion of the LVOT area, as measured by computed tomography (CT), reclassifies the degree of aortic stenosis (AS) and assessed the impact on patient outcome after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Four hundred and twenty-two patients with indexed aortic valve area index (AVAi) of <0.6 cm2 /m2 , assessed by using the classical continuity equation (mean age: 81.5 ± 6.1 years, 51% female, mean left ventricular ejection fraction: 53.2 ± 13.6%), underwent TAVR and were included. After inclusion of the CT measured LVOT area into the continuity equation, the hybrid AVAi led to a reclassification of 30% (n = 128) of patients from severe to moderate AS. Multivariate predictors for reclassification were male sex, lower mean aortic gradient, and lower annulus/LVOT ratio (all p < .01). Reclassified patients had significantly higher sST2 at baseline and higher NT-proBNP values at baseline and 6 months follow-up compared to non-reclassified patients. Acute kidney injury was experienced more frequently after TAVR by reclassified patients, but no significant mortality difference occurred during 2 years of follow-up. CONCLUSION: The hybrid AVAi reclassifies a significant portion of low-gradient severe AS patients into moderate AS. Reclassified patients showed increased fibrosis and heart failure markers at baseline compared to non-reclassified patients. But reclassification had no significant impact on mortality up to 2 years after TAVR. Routine assessment of hybrid AVAi seems not to improve further risk stratification of TAVR patients.

7.
PLoS One ; 15(3): e0230535, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191751

RESUMO

BACKGROUND: Major vascular complications (VCs) of ilio-femoral arterial access after percutaneous coronary interventions are infrequent, but are associated with increased mortality and morbidity. Routine endovascular repair of VCs is becoming the treatment of choice, especially for patients who cannot tolerate vascular surgery due to advanced cardiovascular disease or are in a bailout situation. Here, we review the different types of vascular access site complications associated with percutaneous coronary interventions (PCIs) and assess the safety and efficacy of endovascular treatment. METHODS: Data were retrospectively analysed from patients who experienced VCs after transfemoral PCIs, from December 2014 to May 2018. During this period, out of 2833 patients who underwent femoral coronary interventions, 53 (1.9%) experienced major VCs. RESULTS: In total, 40/53 (75.5%) cases with major VCs led to unplanned endovascular repair and 13/53 (24.5%) cases required surgical repair. VCs included 17 (32.1%) retroperitoneal bleeding events (BARC-2, 3a,b), 20 (37.7%) intimal dissections, and 16 (30.2%) femoral pseudoaneurysms. Overall, 32 (60.4%) patients received a covered stent, two (3.8%) received a nitinol stent, five (9.4%) patients with dissections were treated with prolonged balloon angioplasty alone, and one patient with femoral pseudoaneurysm underwent thrombin injection with simultaneous balloon occlusion. The mean hospital stay for patients after endovascular treatment was 11.06 ± 5.2 days, while for patients after surgical repair it was 17 ± 8.2 days. Endovascularly treated patients were transfused with red blood cells (13/40 32.5% vs. 2/13 15.4%) significantly more often than patients treated surgically, although surgically treated patients received more red blood cell concentrates per unit than endovascularly treated patients (1 ± 0.47 vs. 2 ± 0.93). During the one-year follow-up, no intermittent claudication was reported, and no patient required secondary endovascular or surgical repair. CONCLUSIONS: For patients who cannot tolerate vascular surgery due to advanced cardiovascular disease or are in a bailout situation, endovascular management of VCs following PCIs seems to be a feasible and safe treatment option, and represents an alternative to surgical repair in life-threatening situations. Endovascular treatment was associated with significantly fewer red blood cell concentrates per patient and fewer days in hospital than surgical treatment.

8.
Arterioscler Thromb Vasc Biol ; 40(4): 885-900, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32160774

RESUMO

Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic aortic valve stenosis is still associated with high morbidity and mortality. Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification. To date, no pharmacotherapy has been established to prevent aortic valve calcification. However, novel promising therapeutic targets have been recently identified. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32212302

RESUMO

OBJECTIVES: The purpose of this study was to investigate the impact of periprocedural troponin levels on clinical outcome following the MitraClip procedure. BACKGROUND: Cardiac troponin is known to be a predictive biomarker for various clinical outcomes; however, data about its predictive value in patients undergoing transcatheter mitral valve repair are limited. METHODS: Consecutive patients undergoing the MitraClip procedure were enrolled. Serum cardiac troponin I concentrations were measured before and after the procedure, and the maximal value recorded within 72 hr after the procedure was used for the postprocedural values. The clinical outcome was all-cause mortality within a 1-year follow-up. RESULTS: Out of 354 patients, 29 patients (8.2%) were deceased within 1 year. Patients who died had significantly higher baseline (0.05 [0.01-0.08] vs. 0.01 [0.01-0.03] ng/ml; p < .001) and postprocedural troponin I values (0.51 [0.30-1.42] vs. 0.20 [0.33-0.55] ng/ml; p = .005). A Kaplan-Meier analysis showed that patients with higher baseline troponin I values had a significantly worse prognosis than those with lower values (log-rank p < .001), and similarly, 1-year mortality was significantly higher in patients with higher postprocedural troponin I than those with lower levels (log-rank p = .021). Moreover, the highest mortality rate was observed in patients with both elevated baseline and postprocedural troponin I values (log-rank p = .001), which was found to be an independent predictor of mortality by multivariable analyses. CONCLUSIONS: The present study suggests that combined baseline and postprocedural troponin measurements are useful for risk stratification of 1-year mortality following the MitraClip procedure.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32065722

RESUMO

BACKGROUND: Left atrial (LA) volumes and function are believed to improve following interventional reduction of mitral regurgitation (MR) with MitraClip. However, exact LA alterations after MitraClip in patients with functional MR and functional mitral regurgitation (FMR) are unknown. OBJECTIVES: We aimed to evaluate the effect of MitraClip on LA volumes and global function in patients with FMR and its importance for patients' prognosis. METHODS: All patients underwent three-dimensionally transthoracic echocardiography with an offline evaluation of LA geometry and strain analysis at baseline and follow-up (FU). FU examinations were planned for 6 and 12 months after MitraClip. RESULTS: We prospectively included 50 consecutive surgical high-risk (logistic EuroSCORE: 17.2 ± 13.9%) patients (77 ± 9 years, 22% female) with symptomatic moderate-to-severe to severe functional MR without atrial fibrillation. Echocardiographic evaluation showed that the E/E' ratio was significantly higher at FU (15.6 ± 7.3, 24.1 ± 13.2, p = .05) without relevant changes in systolic left ventricle (LV) function (p = .5). LA volumes (end-diastolic volume [LA-EDV] and end-systolic volume [LA-ESV]) (LA-EDV: 83.1 ± 39.5 ml, 115.1 ± 55.3 ml, p = .012; LA-ESV: 58.4 ± 33.4 ml, 80.1 ± 43.9 ml, p = .031), muscular mass (105.1 ± 49.3 g, 145.4 ± 70.6 g, p = .013), as well as LA stroke volume (24.6 ± 12.5 ml, 34.9 ± 19.1 ml, p = .016) significantly increased after the procedure. LA ejection fraction (LA-EF: 31.7 ± 12.8%, 31.1 ± 12.3%, p = .8) and atrial global strain (aGS: -10.8 ± 5.4%, -9.7 ± 4.45%, p = .4) showed no significant changes at FU. Despite no relevant changes during FU, the baseline aGS was found to be the strongest predictor for mortality and adverse interventional outcome. CONCLUSION: MitraClip increases atrial stroke volume, atrial volumes, and muscular mass in patients with FMR. We found that the baseline aGS the strongest predictor for mortality, rehospitalization, and higher residual MR at FU.

11.
Am Heart J ; 222: 73-82, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32018204

RESUMO

BACKGROUND: Underweight and obesity represent classical risk factors for adverse outcome in patients treated for cardiovascular disease. AIMS: The current analysis examines the impact of underweight, overweight and obesity on intra-hospital, short and long-term outcomes in patients treated by MitraClip therapy. METHODS AND RESULTS: From August 2010 until July 2013, 799 patients (age 75.3 ±â€¯8.6 years, male gender 60.7%, median logistic EuroSCORE 20% [12; 31], functional mitral regurgitation (MR): 69.3%) were prospectively enrolled into the multicenter German Transcatheter Mitral Valve Interventions registry. Patients were stratified according to body mass index (BMI) into 4 groups: BMI <20 kg/m2 (underweight), BMI 20.0 to <25.0 kg/m2 (normal weight, reference group), BMI 25.0 to <30.0 kg/m2 (overweight) and BMI ≥30 kg/m2 (obese). Significant increased rates of procedural failure, transfusion/bleeding, sepsis or multiorgan failure and low cardiac output failure were found for underweight patients only. Kaplan-Meier survival curves demonstrated inferior survival for underweight patients, but comparable outcomes for all other patients (global log rank test, P < .01). Multivariable Cox-regression analysis (adjusted for age, gender, creatinine ≥1.5 mg/dL, diabetes, left ventricular ejection fraction <30% and chronic obstructive pulmonary disease) confirmed underweight (as compared to normal weight) as an independent risk factor of death (hazard ratio [HR]: 1.58, 95% confidence interval (CI): 1.01-2.46, P = .044) and overweight as protective against death (HR: 0.71; 95%-CI: 0.55-0.93; P = .011). CONCLUSIONS: Compared to other weight groups, underweight patients undergoing MitraClip implantation are exposed to increased rates of procedural failure, bleeding and low cardiac output as well as increased short- and long-term mortality rates and should therefore be carefully discussed in the heart-team.

12.
JACC Cardiovasc Interv ; 13(6): 739-747, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32061608

RESUMO

OBJECTIVES: The aim of this study was to investigate the safety and efficacy of coronary protection by preventive coronary wiring and stenting across the coronary ostia in patients at high risk for coronary obstruction after transcatheter aortic valve replacement (TAVR). BACKGROUND: Coronary obstruction following TAVR is a life-threatening complication with high procedural and short-term mortality. METHODS: Data were collected retrospectively from a multicenter international registry between April 2011 and February 2019. RESULTS: Among 236 patients undergoing coronary protection with preventive coronary wiring, 143 had eventually stents implanted across the coronary ostia after valve deployment. At 3-year follow-up, rates of cardiac death were 7.8% in patients receiving stents and 15.7% in those not receiving stents (adjusted hazard ratio: 0.42; 95% confidence interval: 0.14 to 1.28; p = 0.13). There were 2 definite stent thromboses (0.9%) in patients receiving stents, both occurring after TAVR in "valve-in-valve" procedures. In patients not receiving stents, there were 4 delayed coronary occlusions (DCOs) (4.3%), occurring from 5 min to 6 h after wire removal. Three cases occurred in valve-in-valve procedures and 1 in a native aortic valve procedure. Distance between the virtual transcatheter valve and the protected coronary ostia <4 mm was present in 75.0% of patients with DCO compared with 30.4% of patients without DCO (p = 0.19). CONCLUSIONS: In patients undergoing TAVR at high risk for coronary obstruction, preventive stent implantation across the coronary ostia is associated with good mid-term survival rates and low rates of stent thrombosis. Patients undergoing coronary protection with wire only have a considerable risk for DCO.

13.
Clin Res Cardiol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020270

RESUMO

BACKGROUND: There are still limited data regarding transcatheter aortic valve implantation (TAVI) endocarditis. OBJECTIVES: The objective of the present study was to investigate the predictor and long-term outcome of TAVI endocarditis. METHODS: Consecutive patients undergoing TAVI at the University of Bonn were prospectively enrolled in this study. Transcatheter heart valve (THV) endocarditis was defined according to Duke criteria. The primary outcome was all-cause death within a 5-year follow-up. RESULTS: 1448 successful TAVI patients were eligible for the study and 17 patients (1.2%) developed THV endocarditis during the follow-up period (median 294 days). A multivariable logistic regression analysis identified age (odds ratio [OR] 0.90; P = 0.001) and residual paravalvular leakage (PVL) ≥ 2 after TAVI (OR 5.15; P = 0.015) as the main predictors for the occurrence of TAVI endocarditis. Additional analyses revealed that younger patients were significantly associated with higher rates of diabetes (P = 0.001), hemodialysis (P < 0.001), prior cardiac surgery (P < 0.001), and chronic obstructive pulmonary disease (COPD) (P < 0.001). A Kaplan-Meier analysis showed a significantly worse prognosis in TAVI patients with endocarditis than in patients without (log-rank; P = 0.03) during the 5-year follow-up. A multivariable Cox proportional hazard analysis revealed that TAVI endocarditis is an independent predictor of long-term mortality (hazard ratio 4.17; 95% CI 1.91-9.07; P < 0.001). CONCLUSIONS: Our study identified lower age and residual PVL ≥ 2 as predictors for THV endocarditis, which itself may be considered as an independent predictor of long-term mortality after TAVI.

14.
Clin Res Cardiol ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32072264

RESUMO

BACKGROUND: The benefit of TAVI in cancer patients is currently unclear. OBJECTIVES: The purpose of this study is to investigate prognostic impact of cancer status (active cancer or previous cancer) in severe aortic stenosis (AS) patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: Consecutive TAVI patients in the Heart Center Bonn were enrolled and we stratified the patients into three groups: current cancer (active cancer), non-current cancer (previous cancer), or no cancer. The primary outcome was all-cause death within a 5-year follow-up. We evaluated mean aortic pressure gradient (mPG) values following TAVI (baseline mPG) and at the final follow-up (follow-up mPG). RESULTS: In total, 1568 TAVI patients were eligible and 298 patients (19.0%) had active or previous cancer. At the 5-year follow-up, cancer patients had a significantly worse prognosis than non-cancer patients (log rank, P < 0.001). In a multivariable analysis, previous cancer was a significant predictor for 5-year mortality (hazard ratio [HR], 1.56; P < 0.001). Estimated mortality rates at 5-year follow-up rates among active cancer, previous cancer, and non-cancer were 84.0%, 65.8%, and 50.2% (long-rank P < 0.001), respectively. The hazard ratios of active cancer and previous cancer for 5-year mortality were 2.79 (P < 0.001) and 1.38 (P = 0.019) compared to non-cancer patients. We found significantly higher mPG during follow-up than at baseline in cancer patients (follow-up 8.10 vs baseline 7.40 mmHg; Wilcoxon P = 0.012). CONCLUSIONS: Active, and also previous, cancer status are associated with less beneficial long-term prognosis in TAVI patients.

17.
Basic Res Cardiol ; 115(2): 18, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980946

RESUMO

Circulating sca1+/flk1+ cells are hypothesized to be endothelial progenitor cells (EPCs) in mice that contribute to atheroprotection by replacing dysfunctional endothelial cells. Decreased numbers of circulating sca1+/flk1+ cells correlate with increased atherosclerotic lesions and impaired reendothelialization upon electric injury of the common carotid artery. However, legitimate doubts remain about the identity of the putative EPCs and their contribution to endothelial restoration. Hence, our study aimed to establish a phenotype for sca1+/flk1+ cells to gain a better understanding of their role in atherosclerotic disease. In wild-type mice, sca1+/flk1+ cells were mobilized into the peripheral circulation by granulocyte-colony stimulating factor (G-CSF) treatment and this movement correlated with improved endothelial regeneration upon carotid artery injury. Multicolor flow cytometry analysis revealed that sca1+/flk1+ cells predominantly co-expressed surface markers of conventional B cells (B2 cells). In RAG2-deficient mice and upon B2 cell depletion, sca1+/flk1+ cells were fully depleted. In the absence of monocytes, sca1+/flk1+ cell levels were unchanged. A PCR array focused on cell surface markers and next-generation sequencing (NGS) of purified sca1+/flk1+ cells confirmed their phenotype to be predominantly that of B cells. Finally, the depletion of B2 cells, including sca1+/flk1+ cells, in G-CSF-treated wild-type mice partly abolished the endothelial regenerating effect of G-CSF, indicating an atheroprotective role for sca1+/flk1+ B2 cells. In summary, we characterized sca1+/flk1+ cells as a subset of predominantly B2 cells, which are apparently involved in endothelial regeneration.

18.
Cardiovasc Interv Ther ; 35(1): 62-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31396890

RESUMO

Percutaneous mitral and tricuspid valve interventions are alternative treatment options for patients who are deemed to be at high surgical risk and/or inoperable. Transcatheter edge-to-edge mitral valve repair using the MitraClip and PASCAL system, which are designed to mimic the surgical Alfieri's stich, has changed the landscape for the treatment of symptomatic functional mitral regurgitation (MR). Previous studies have shown that the procedure can reduce symptoms and improve functional capacity with low rates of complication. Recently, two randomized controlled clinical trials have reported the effect of the MitraClip on outcomes for secondary MR. Next-generation devices, advanced techniques, and additional clinical data would further improve the outcomes following this procedure. Percutaneous direct annuloplasty using the Cardioband system is a relatively new technique that closely resembles surgical annuloplasty. Its role in treating secondary MR as well as its concomitant use with edge-to-edge mitral repair will continue to gain attention. The transapical off-pump mitral valve repair with neochord implantation, known as a NeoChord procedure, is also a new option to implant artificial chords in a minimally invasive manner in MR patients with leaflet prolapse or flail. Transcatheter mitral valve replacement is another emerging treatment option for selected patients. Although the development of transcatheter strategies for tricuspid regurgitation (TR) is still in the early stages, there is growing evidence to support the application of various approaches, including edge-to-edge repair and annuloplasty, to address unmet needs. In this review article, we will summarize the emerging minimally invasive interventions for mitral and tricuspid valves.

19.
Vasa ; 49(1): 57-62, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31364499

RESUMO

Background: Pseudoxanthoma elasticum (PXE) is a heritable recessive disease characterized by calcification and fragmentation of soft connective tissue. Besides progressive loss of vision, alternations of the skin, and early-onset atherosclerosis different reports have suggested a microvascular manifestation of PXE and restrictive lung disease. Aim of this study was to elaborate a specific pattern of capillary alterations in PXE as well as to contemplate a possible connection to restrictive lung disease. Patients and methods: 53 consecutive patients with PXE and 26 controls were studied. All patients underwent nailfold capillaroscopy, body plethysmography, capillary blood gas analysis, and venous puncture to assess titer of autoantibodies. Results: PXE was associated with highly pathological alterations of capillaries compared to control. Atypical capillaries, such as ramifications and bushy forms, as well as dilatations varied at highest significance (p < .001). This effect was mirrored by perivascular edema, density and tortuous capillaries. Titer of anti-nuclear autoantibodies were not elevated in patients with PXE. Further analysis revealed negative correlation between vital capacity and presence of atypical capillaries. Conclusions: This study firstly describes the pattern of nailfold capillaries in PXE. Capillaries are highly pathological and consist of ramifications and bushy forms as well as dilatations. Frequently, tortuous capillaries, pericapillary edema and reduced denseness of capillary loops occur. Frequency of atypical capillaries is negatively correlated with vital capacity which can be interpreted as further lead on restrictive lung disease.


Assuntos
Pseudoxantoma Elástico , Humanos , Angioscopia Microscópica , Pele
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