Fortgeführte versus unterbrochene orale Antikoagulation bei transfemoralem Transkatheteraortenklappenersatz und der Einfluss des perioperativen Antikoagulationsmanagements auf Morbidität und Mortalität bei Patienten mit Vorhofflimmern

Die hochgradige Aortenklappenstenose ist die häufigste therapiebedürftige Klappenerkrankung in Europa. Mit steigendem Lebensalter geht ein erhöhtes operatives Risiko einher, sodass sich der minimalinvasive, transferorale Transkatheteraortenklappenersatz (TAVI) in den letzten Jahren zu einem etablierten Therapieverfahren entwickelte. Mit steigendem Alter erhöht sich ebenfalls die Prävalenz eines Vorhofflimmerns, woraus sich in der Regel die Indikation zur oralen Antikoagulation ergibt. Der Umgang mit einer oralen Antikoagulation in einem periinterventionellen Setting bei TAVI steht im Spannungsfeld von erwartetem Blutungs- und thrombembolischem Risiko. In dieser Arbeit wurden retrospektiv anhand eines monozentrischen Registers am Herzzentrum Leipzig unterschiedliche Antikoagulationsregime in Hinblick auf einen kombinierten Sicherheitsendpunkt anhand der VARC 2 Kriterien nach 30 Tagen und die 1-Jahresmortalität untersucht.:1 Einleitung 1.1 Prävalenz und Prognose der Aortenklappenstenose 1.2 Ätiologie und Pathogenese der Aortenklappenstenose 1.3 Therapiemöglichkeiten der hochgradigen Aortenklappenstenose 1.3.1 medikamentöse Therapie 1.3.2 perkutane Ballonvalvuloplastie 1.3.3 offen- chirurgischer Aortenklappenersatz 1.3.4 interventioneller Aortenklappenersatz 1.4 Therapieplanung zur Behandlung der Aortenklappenstenose 1.5 Vorhofflimmern als Komorbidität 1.5.1 Rationale zur oralen Antikoagulation und Risikostratifizierung bei Vorhofflimmern 1.6 orale Antikoagulation 1.6.1 Vitamin K Antagonisten 1.6.2 Direkte orale Antikoagulanzien 1.7 Periinterventioneller Umgang mit einer oralen Antikoagulation 1.8 Komplikationen bei TAVI Eingriffen 1.8.1 zerebral-embolische Komplikationen 1.8.2 Blutungskomplikationen 1.9 Einordnung von periprozeduralen Komplikationen anhand der VARC-2 Kriterien 1.10 Aufbau des TAVI Registers am Herzzentrum Leipzig 1.11 Datenerhebung 1.12 Zielsetzung 2 Publikationsmanuskript 2.1 Allgemeine Information 2.2 Manuskript 3 Zusammenfassun

Fortgeführte versus unterbrochene orale Antikoagulation bei transfemoralem Transkatheteraortenklappenersatz und der Einfluss des perioperativen Antikoagulationsmanagements auf Morbidität und Mortalität bei Patienten mit Vorhofflimmern

Die hochgradige Aortenklappenstenose ist die häufigste therapiebedürftige Klappenerkrankung in Europa. Mit steigendem Lebensalter geht ein erhöhtes operatives Risiko einher, sodass sich der minimalinvasive, transferorale Transkatheteraortenklappenersatz (TAVI) in den letzten Jahren zu einem etablierten Therapieverfahren entwickelte. Mit steigendem Alter erhöht sich ebenfalls die Prävalenz eines Vorhofflimmerns, woraus sich in der Regel die Indikation zur oralen Antikoagulation ergibt. Der Umgang mit einer oralen Antikoagulation in einem periinterventionellen Setting bei TAVI steht im Spannungsfeld von erwartetem Blutungs- und thrombembolischem Risiko. In dieser Arbeit wurden retrospektiv anhand eines monozentrischen Registers am Herzzentrum Leipzig unterschiedliche Antikoagulationsregime in Hinblick auf einen kombinierten Sicherheitsendpunkt anhand der VARC 2 Kriterien nach 30 Tagen und die 1-Jahresmortalität untersucht.:1 Einleitung 1.1 Prävalenz und Prognose der Aortenklappenstenose 1.2 Ätiologie und Pathogenese der Aortenklappenstenose 1.3 Therapiemöglichkeiten der hochgradigen Aortenklappenstenose 1.3.1 medikamentöse Therapie 1.3.2 perkutane Ballonvalvuloplastie 1.3.3 offen- chirurgischer Aortenklappenersatz 1.3.4 interventioneller Aortenklappenersatz 1.4 Therapieplanung zur Behandlung der Aortenklappenstenose 1.5 Vorhofflimmern als Komorbidität 1.5.1 Rationale zur oralen Antikoagulation und Risikostratifizierung bei Vorhofflimmern 1.6 orale Antikoagulation 1.6.1 Vitamin K Antagonisten 1.6.2 Direkte orale Antikoagulanzien 1.7 Periinterventioneller Umgang mit einer oralen Antikoagulation 1.8 Komplikationen bei TAVI Eingriffen 1.8.1 zerebral-embolische Komplikationen 1.8.2 Blutungskomplikationen 1.9 Einordnung von periprozeduralen Komplikationen anhand der VARC-2 Kriterien 1.10 Aufbau des TAVI Registers am Herzzentrum Leipzig 1.11 Datenerhebung 1.12 Zielsetzung 2 Publikationsmanuskript 2.1 Allgemeine Information 2.2 Manuskript 3 Zusammenfassun

RRR - Mazar_Srull - Crusius_Blatz

Our laboratory's Implementation of the Mazar_Srull RRR protoco

Telescopes and microscopes of motivation: Emulative goals in admiration and envy differ in abstractness and temporal orientation

Admiration and envy both stem from perceiving superior others. A recent debate centers on the motivational qualities of these emotions. Some scholars argue that, compared to admiration, envy is characterized by a stronger motivation to self-improve by emulating upward comparison standards. Mounting evidence suggests, however, that both admiration and (benign) envy can involve upward motivation. Yet, whether and how their motivational characteristics can be distinguished is unclear. We propose that emulative goals in admiration and envy differ in terms of their abstractness, explaining inconsistencies in prior research and pointing toward complementary functions of admiration and envy. In Study 1 (N = 193), participants recalled and re-experienced episodes of admiration or benign envy and listed goals elicited in these episodes. Additionally, in Study 2 (N = 416), some participants recalled episodes of malicious envy. Participants and blinded, external raters evaluated the concreteness versus abstractness of the goals. Furthermore, we assessed the goals’ temporal orientation. The results support that upward motivation in admiration is abstract and oriented toward improving in the long term, whereas upward motivation in benign envy involves specific goals and is oriented toward short-term gains. These findings suggest that admiration and envy fulfill their motivational functions in different ways

Safety and Efficacy of Transcatheter Aortic Valve Replacement With Continuation of Vitamin K Antagonists or Direct Oral Anticoagulants.

OBJECTIVES The authors investigated whether transcatheter aortic valve replacement (TAVR) with periprocedural continuation of oral anticoagulation is equally safe and efficacious as TAVR with periprocedural interruption of anticoagulation. BACKGROUND A significant proportion of patients undergoing TAVR have an indication for long-term oral anticoagulation. The optimal periprocedural management of such patients is unknown. METHODS Consecutive patients on oral anticoagulation who underwent transfemoral TAVR at 5 European centers were enrolled. Oral anticoagulation was either stopped 2 to 4 days before TAVR or continued throughout the procedure. Primary safety outcome was major bleeding. Secondary efficacy endpoints included vascular complications, stroke, and mortality. RESULTS Of 4,459 patients, 584 patients were treated with continuation of anticoagulation and 733 with interruption of anticoagulation. At 30 days, major or life-threatening bleedings occurred in 66 (11.3%) versus 105 (14.3%; odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.61 to 1.21; p = 0.39) and major vascular complications in 64 (11.0%) versus 90 (12.3%; OR: 0.89, CI: 0.62 to 1.27; p = 0.52) of patients with continuation and with interruption of anticoagulation, respectively. Transfusion of packed red blood cells was less often required in patients with continuation of anticoagulation (80 [13.7%] vs. 130 [17.7%]; OR: 0.59, 95% CI: 0.42 to 0.81; p = 0.001). Kaplan-Meier estimates of survival at 12 months were 85.3% in patients with continuation of anticoagulation and 84.0% in patients with interruption of anticoagulation (hazard ratio: 0.90, 95% CI: 0.73 to 1.12; p = 0.36). CONCLUSIONS Continuation of oral anticoagulation throughout TAVR did not increase bleeding or vascular complication rates. Moreover, packed red blood cell transfusions were less often required in patients with continuation of oral anticoagulation

Continued non-vitamin K antagonist oral anticoagulants versus vitamin K antagonists during transcatheter aortic valve implantation

BACKGROUND One-third of patients undergoing transcatheter aortic valve implantation (TAVI) have an indication for long-term oral anticoagulation (OAC). AIMS We aimed to investigate whether continued non-vitamin K antagonist oral anticoagulant (NOAC) therapy compared with continued vitamin K antagonist (VKA) therapy during TAVI is equally safe and effective.  Methods: Consecutive patients on OAC with either NOAC or VKA undergoing transfemoral TAVI at five European centres were enrolled. The primary outcome measure was a composite of major/life-threatening bleeding, stroke, and all-cause mortality at 30 days. RESULTS In total, 584 patients underwent TAVI under continued OAC with 294 (50.3%) patients receiving VKA and 290 (49.7%) patients receiving NOAC. At 30 days, the composite primary outcome had occurred in 51 (17.3%) versus 36 (12.4%) patients with continued VKA and with continued NOAC, respectively (odds ratio [OR] 0.68, 95% confidence interval [CI]: 0.43-1.07; p=0.092). Rates of major/life-threatening bleeding (OR 0.87, 95% CI: 0.52-1.47; p=0.606) and stroke (OR 1.02, 95% CI: 0.29-3.59; p=0.974) were not different between groups. In a multivariate Cox regression analysis, continued NOAC, compared with continued VKA, was associated with a lower risk for all-cause 1-year mortality (hazard ratio [HR] 0.61, 95% CI: 0.37-0.98; p=0.043). The analysis of the propensity score-matched cohort revealed similar results. CONCLUSIONS Continued NOAC compared with continued VKA during TAVI led to comparable outcomes with regard to the composite outcome measure indicating that continued OAC with both drugs is feasible. These hypothesis-generating results need to be confirmed by a dedicated randomised controlled trial

A glucocorticoid receptor gene haplotype (TthIII1/ER22/23EK/9beta) is associated with a more aggressive disease course in multiple sclerosis.

Item does not contain fulltextCONTEXT: In patients with multiple sclerosis (MS), glucocorticoids (GCs) might not be sufficiently able to restrain the immune system, possibly due to decreased GC sensitivity. This may be, at least partially, genetically determined. Previously, we reported a more aggressive disease course in patients with the glucocorticoid receptor (GR) gene ER22/23EK polymorphism, which has been shown to decrease GC sensitivity. OBJECTIVE: In 646 MS patients and 317 healthy controls, we investigated whether haplotypes, including the ER22/23EK polymorphism or the GR 9beta polymorphism, which is also associated with a relative GC resistance, were associated with a more aggressive disease course. PATIENTS AND METHODS: Polymorphisms in the GR gene (9beta, ER22/23EK, TthIIII, BclI, and N363S), which have previously been associated with altered GC sensitivity were determined and haplostructure was characterized. We evaluated whether the haplotypes were associated with disease susceptibility and several other disease characteristics. The association with disease progression was analyzed using Cox regression with time to Expanded Disability Status Score 6 as outcome. RESULTS: None of the haplotypes was associated with disease susceptibility, age at onset, or onset type. Haplotype 6 (TthIIII, ER2223EK, and 9beta-G) was associated with a more rapid disease progression (hazard ratio 2.3; 95% confidence interval 1.5-3.7; P < 0.001). This seems to result from the presence of ER22/23EK, and not from the 9beta and TthIIII polymorphisms. CONCLUSIONS: MS patients carrying the haplotype 6 (TthIIII, ER22/23EK, and 9beta) have a more aggressive disease course. This is probably due to the presence of the polymorphism ER22/23EK, which causes a decreased GC sensitivity

Sex Differences in Infective Endocarditis After Transcatheter Aortic Valve Replacement

International audienceBackground: Outcomes after transcatheter aortic valve replacement (TAVR) and infectious diseases may vary according to sex.Methods: This multicentre study aimed to determine the sex differences in clinical characteristics, management, and outcomes of infective endocarditis (IE) after TAVR. A total of 579 patients (217 women, 37.5%) who had the diagnosis of definite IE following TAVR were included retrospectively from the Infectious Endocarditis After TAVR International Registry.Results: Women were older (80 ± 8 vs 78 ± 8 years; P = 0.001) and exhibited a lower comorbidity burden. Clinical characteristics and microbiological profiles were similar between men and women, but culture-negative IE was more frequent in women (9.9% vs 4.3%; P = 0.009). A high proportion of patients had a clinical indication for surgery (54.4% in both groups; P = 0.99), but a surgical intervention was performed in a minority of patients (women 15.2%, men 20.3%; P = 0.13). The mortality rate at index IE hospitalisation was similar in both groups (women 35.4%, men 31.7%; P = 0.37), but women exhibited a higher mortality rate at 2-year follow-up (63% vs 52.1%; P = 0.021). Female sex remained an independent risk factor for cumulative mortality in the multivariable analysis (adjusted HR 1.28, 95% CI 1.02-1.62; P = 0.035). After adjustment for in-hospital events, surgery was not associated with better outcomes in women.Conclusions: There were no significant sex-related differences in the clinical characteristics and management of IE after TAVR. However, female sex was associated with increased 2-year mortality risk

Incidence, Clinical Characteristics, and Impact of Absent Echocardiographic Signs in Patients with Infective Endocarditis after Transcatheter Aortic Valve Implantation

International audienceBackground: Echocardiography is the primary imaging modality for diagnosis of infective endocarditis (IE) in prosthetic valve endocarditis (PVE) including IE after transcatheter aortic valve implantation (TAVI). This study aimed to evaluate the characteristics and clinical outcomes of patients with absent compared with evident echocardiographic signs of TAVI-IE.Methods: Patients with definite TAVI-IE derived from the Infectious Endocarditis after TAVI International Registry were investigated comparing those with absent and evident echocardiographic signs of IE defined as vegetation, abscess, pseudoaneurysm, intracardiac fistula or valvular perforation or aneurysm.Results: Among 578 patients, 87 (15.1%) and 491 (84.9%) had absent (IE-neg) and evident (IE-pos) echocardiographic signs of IE, respectively. IE-neg were more often treated via a transfemoral access with a self-expanding device, and had higher rates for peri-interventional complications (e.g. stroke, major vascular complications) during the TAVI procedure (p < 0.05 for all). IE-neg had higher rates of IE caused by staphylococcus aureus (33.7% vs. 23.2%, p = 0.038) and enterococci (37.2% vs. 23.8%, p = 0.009), but lower rates of coagulase-negative staphylococci (4.7% vs. 20.0%, p = 0.001).IE-neg was associated with the same dismal prognosis for in-hospital mortality in a multivariate binary regression analysis (OR 1.51, 95%-CI 0.55-4.12) as well as a for 1-year mortality in a Cox regression analysis (HR 1.10, 95%-CI 0.67-1.80).Conclusions: Even with negative echocardiographic imaging, patients who have undergone TAVI and presenting with positive blood cultures and symptoms of infection are a high-risk patient group having a reasonable suspicion of IE and the need for an early treatment initiation