Publications by authors named "P Christian Schulze"

489 Publications

Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart.

Clin Res Cardiol 2021 Jun 10. Epub 2021 Jun 10.

Department of Cardiology, Kerckhoff-Klinik GmbH, Benekestr 2-8, 61231, Bad Nauheim, Germany.

Objective: We sought to explore whether classification of patients with heart failure and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) according to their left ventricular ejection fraction (LVEF) identifies differences in their exercise hemodynamic profile, and whether classification according to an index of right ventricular (RV) function improves differentiation.

Background: Patients with HFmrEF and HFpEF have hemodynamic compromise on exertion. The classification according to LVEF implies a key role of the left ventricle. However, RV involvement in exercise limitation is increasingly recognized. The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PASP) ratio is an index of RV and pulmonary vascular function. Whether exercise hemodynamics differ more between HFmrEF and HFpEF than between TAPSE/PASP tertiles is unknown.

Methods: We analyzed 166 patients with HFpEF (LVEF ≥ 50%) or HFmrEF (LVEF 40-49%) who underwent basic diagnostics (laboratory testing, echocardiography at rest, and cardiopulmonary exercise testing [CPET]) and exercise with right heart catheterization. Hemodynamics were compared according to echocardiographic left ventricular or RV function.

Results: Exercise hemodynamics (e.g. pulmonary arterial wedge pressure/cardiac output [CO] slope, CO increase during exercise, and maximum total pulmonary resistance) showed no difference between HFpEF and HFmrEF, but significantly differed across TAPSE/PASP tertiles and were associated with CPET results. N-terminal pro-brain natriuretic peptide concentration also differed significantly across TAPSE/PASP tertiles but not between HFpEF and HFmrEF.

Conclusion: In patients with HFpEF or HFmrEF, TAPSE/PASP emerged as a more appropriate stratification parameter than LVEF to predict clinically relevant impairment of exercise hemodynamics. Stratification of exercise hemodynamics in patients with HFpEF or HFmrEF according to LVEF or TAPSE/PASP, showing significant distinctions only with the RV-based strategy. All data are shown as median [upper limit of interquartile range] and were calculated using the independent-samples Mann-Whitney U test or Kruskal-Wallis test. PVR pulmonary vascular resistance; max maximum level during exercise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00392-021-01884-1DOI Listing
June 2021

Deoxyribonuclease is prognostic in patients undergoing transcatheter aortic valve replacement.

Eur J Clin Invest 2021 Jun 8:e13595. Epub 2021 Jun 8.

Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.

Degenerative aortic valve stenosis is an inflammatory process that resembles atherosclerosis. Neutrophils release their DNA upon activation and form neutrophil extracellular traps (NETs), which are present on degenerated aortic valves. NETs correlate with pressure gradients in severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is an established treatment option for aortic valve stenosis. Bioprosthetic valve deterioration promoted by inflammatory, fibrotic and thrombotic processes limits outcome. Deoxyribonuclease is a natural counter mechanism to degrade DNA in circulation. In the present observational study, we investigated plasma levels of double-stranded DNA, deoxyribonuclease activity and outcome after TAVR. 345 consecutive patients undergoing TAVR and 100 healthy reference controls were studied. Double-stranded DNA was measured by fluorescence assays in plasma obtained at baseline and after TAVR. Deoxyribonuclease activity was measured at baseline using single radial enzyme diffusion assays. Follow-up was performed at 12 months, and mean aortic pressure gradient and survival were evaluated. Receiver operating characteristic, Kaplan-Meier curves and Cox regression models were calculated. Baseline double-stranded DNA in plasma was significantly higher compared to healthy controls, was increased at 3 and 7 days after TAVR, and declined thereafter. Baseline deoxyribonuclease activity was decreased compared to healthy controls. Interestingly, low deoxyribonuclease activity correlated with higher C-reactive protein and higher mean transaortic gradient after 12 months. Finally, deoxyribonuclease activity was a strong independent predictor of outcome 12 months after TAVR. Deoxyribonuclease activity is a potential biomarker for risk stratification after TAVR. Pathomechanisms of bioprosthetic valve deterioration involving extracellular DNA and deoxyribonuclease merit investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eci.13595DOI Listing
June 2021

The impact of tricuspid annular geometry on outcome after percutaneous edge-to-edge repair for severe tricuspid regurgitation.

Cardiol J 2021 May 4. Epub 2021 May 4.

Klinik für Innere Medizin I, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany.

Background: Percutaneous tricuspid repair using the edge-to-edge technique is a novel treatment option. More data are needed to better understand which aspects predict a favorable outcome METHODS: Twenty high-risk patients (78.6 ± 8.3 years, EUROScore II 9.1 ± 7.7%, STS score 8.8 ± 4.3) with severe symptomatic tricuspid regurgitation (TR) were treated with the MitraClip® system. All patients underwent standardized pre-, peri-, and post-procedural evaluation. Acute success was defined as successful edge-to-edge repair with TR reduction of ≥ 1 grade and survival until hospital discharge.

Results: Fifteen (75%) patients showed acute success until discharge and 12 (60%) at 30-day follow-up. In 5 (25%) patients repair failed due to either unsuccessful clip implantation (n = 2), single leaflet device attachment (n = 1), TR reduction < 1 grade (n = 1), or in-hospital death (n = 1). Comparing patients with successful procedure versus those with failed repair revealed similar comorbidities but more severe right heart failure, lower left ventricular ejection fraction, worse renal function, and higher diuretic equivalent doses in the failed repair group. No differences in conventional echocardiographic parameters for TR severity but more dilated tricuspid annulus geometry (tricuspid valve [TV] annulus, coaptation depth, tenting area) in the failed repair group were observed. The success rate of non-central/non-anteroseptal jet location was only 25%.

Conclusions: Tricuspid annulus geometry assessment may be of crucial importance and seems to impact procedural outcomes in patients undergoing edge-to-edge TV repair. Further investigations including advanced imaging are needed to better understand and treat this complex valve disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5603/CJ.a2021.0046DOI Listing
May 2021

Delayed Improvement of Depression and Anxiety after Transcatheter Aortic Valve Implantation (TAVI) in Stages of Extended Extra-Valvular Cardiac Damage.

J Clin Med 2021 Apr 8;10(8). Epub 2021 Apr 8.

Department of Internal Medicine I, Jena University Hospital, Friedrich Schiller University, 07747 Jena, Germany.

Background: Depression and anxiety are frequently occurring and likely to be linked to the severity of cardiac diseases like aortic stenosis (AS). This seems to be of interest since a staging classification of extra-valvular cardiac damage in AS has been introduced and shown to be of prognostic relevance.

Objective: The current study aimed to investigate the frequency of depression and anxiety in association to staging and their dynamics after transcatheter aortic valve implantation (TAVI).

Methods: A total number of 224 AS patients undergoing TAVI were classified according to the 2017 staging classification into stage 0 to 4 and further dichotomized into group A (stage 0 to 2) and B (stage 3 and 4). Using the Hospital Anxiety and Depression Scale (HADS-D), patients were assigned to depressive versus non-depressive or anxious versus non-anxious per staging group respectively, and analyzed at baseline, 6 weeks, 6 months and 12 months after TAVI.

Results: After dichotomization, 158 patients (70.5%) were assigned to group A and 66 patients (29.5%) to group B. The part showing pathologic values for depression was 25.4% (57/224 patients) in the entire collective, 26.6% (42/158 patients) in group A and 22.7% (15/66 patients) in group B ( = n.s.). The proportion showing pathologic values for anxiety was 26.8% (60/224 patients) in the entire collective and did not differ between group A (24.7%, 39/158 patients) and B (31.8%, 21/66 patients) ( = n.s.). In patients revealing pathologic values for depression or anxiety prior to TAVI, there were significant and stable improvements over time observable already in short-term (6 weeks) follow-up in group A, and likewise, but later, in long-term (6/12 months) follow-up in group B.

Conclusions: Although of proven prognostic relevance, higher stages of extra-valvular cardiac damage are not associated with higher rates of pre-existing depression or anxiety. The TAVI procedure resulted in a persisting reduction of depression and anxiety in patients showing pathologic values at baseline. Notably, these improvements are timely delayed in higher stages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10081579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070529PMC
April 2021

Therapeutic Evaluation of Antibody-Based Targeted Delivery of Interleukin 9 in Experimental Pulmonary Hypertension.

Int J Mol Sci 2021 Mar 27;22(7). Epub 2021 Mar 27.

Department of Internal Medicine I, Univerisity Hospital Jena, 07747 Jena, Germany.

Background And Aims: Pulmonary hypertension (PH) is a heterogeneous disorder associated with poor prognosis. For the majority of patients, only limited therapeutic options are available. Thus, there is great interest to develop novel treatment strategies focusing on pulmonary vascular and right ventricular remodeling. Interleukin 9 (IL9) is a pleiotropic cytokine with pro- and anti-inflammatory functions. The aim of this study was to evaluate the therapeutic activity of F8IL9F8 consisting of IL9 fused to the F8 antibody, specific to the alternatively-spliced EDA domain of fibronectin, which is abundantly expressed in pulmonary vasculature and right ventricular myocardium in PH.

Methods: The efficacy of F8IL9F8 in attenuating PH progression in the monocrotaline mouse model was evaluated in comparison to an endothelin receptor antagonist (ERA) or an IL9 based immunocytokine with irrelevant antibody specificity (KSFIL9KSF). Treatment effects were assessed by right heart catheterization, echocardiography as well as histological and immunohistochemical tissue analyses.

Results: Compared to controls, systolic right ventricular pressure (RVPsys) was significantly elevated and a variety of right ventricular echocardiographic parameters were significantly impaired in all MCT-induced PH groups except for the F8IL9F8 group. Both, F8IL9F8 and ERA treatments lead to a significant reduction in RVPsys and an improvement of echocardiographic parameters when compared to the MCT group not observable for the KSFIL9KSF group. Only F8IL9F8 significantly reduced lung tissue damage and displayed a significant decrease of leukocyte and macrophage accumulation in the lungs and right ventricles.

Conclusions: Our study provides first pre-clinical evidence for the use of F8IL9F8 as a new therapeutic agent for PH in terms of a disease-modifying concept addressing cardiovascular remodeling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22073460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037792PMC
March 2021