Delayed improvement of depression and anxiety after transcatheter aortic valve implantation (TAVI) in stages of extended extra-valvular cardiac damage

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 (p = 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) (p = 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 stage

Prognostic relevance of mitral and tricuspid regurgitation after transcatheter aortic valve implantation: Impact of follow-up time point for decision-making

Background: In patients with aortic stenosis treated by transcatheter aortic valve implantation (TAVI), mitral and tricuspid regurgitation (MR and TR) at baseline and after TAVI are likely to be of prognostic relevance, and questions such as whether and when treatment further improves prognosis in these patients arise. Aims: Against that background, the purpose of this study was to analyze a variety of clinical characteristics including MR and TR with respect to their potential value as predictors of 2-year mortality after TAVI. Methods: A cohort of 445 typical TAVI patients was available for the study and clinical characteristics were evaluated baseline, 6 to 8 weeks as well as 6 months after TAVI. Results: In 39% of the patients relevant (moderate or severe) MR and in 32% of the patients relevant (moderate or severe) TR could be detected at baseline. The rates were 27% for MR ( p  = 0.001, compared to baseline) and 35% for TR ( p  = n.s., compared to baseline) at the 6- to 8-week follow-up. After 6 months, relevant MR was observable in 28% ( p  = 0.036, compared to baseline) and relevant TR in 34% ( p  = n.s., compared to baseline) of the patients. As predictors of 2-year mortality, a multivariate analysis identified the following parameters for the different time points: sex, age, AS entity, atrial fibrillation, renal function, relevant TR, systolic pulmonary artery pressure (PAPsys), and 6-min walk distance at baseline; clinical frailty scale and PAPsys 6–8 weeks after TAVI and BNP and relevant MR 6 months after TAVI. There was a significantly worse 2-year survival in patients with relevant TR at baseline (68.4% vs. 82.6%, p  < 0.001; whole population, n  = 445) and in patients with relevant MR at 6 months (87.9% vs. 95.2%, p  = 0.042; landmark analysis: n  = 235). Conclusion: This real-life study demonstrated the prognostic relevance of repeated evaluation of MR and TR before and after TAVI. Choosing the right time point for treatment is a remaining clinical challenge, which should be further addressed in randomized trials

Assoziationen zwischen sozialem Status und Behandlungsergebnissen bei Patienten mit Diabetes mellitus Typ 1 und Typ 2

Die Assoziationen zwischen dem Sozialstatus und der Behandlungsqualität von Patienten mit Diabetes mellitus wurden bereits mehrfach untersucht. Es konnte gezeigt werden, dass Patienten mit einem niedrigen Sozialstatus schlechtere Stoffwechselparameter aufweisen und häufiger an Spätkomplikationen erkranken. In keiner der bisher publizierten Studien wurde der Einfluss einer langjährigen Behandlung auf diese, durch soziale Ungleichheiten verursachten, gesundheitlichen Nachteile untersucht. Ziel dieser Arbeit war es herauszufinden, ob in einer mittelthüringischen ambulanten Versorgungseinrichtung ebenfalls Assoziationen zwischen sozialem Status und den Behandlungsergebnissen, bei Patienten mit Diabetes mellitus Typ 1 und Typ 2, bestehen. Um zu ermitteln, ob eventuelle Nachteile durch eine langjährige Behandlung in einem tertiären Versorgungszentrum ausgeglichen werden können, wurde die aktuelle Behandlungsqualität, sowie die Behandlungsqualität zum Zeitpunkt des ersten ambulanten oder stationären Besuches beurteilt

Serum Liberation of Fetal Fibronectin Variants in Patients with Pulmonary Hypertension: ED-A+ Fn as Promising Novel Biomarker of Pulmonary Vascular and Right Ventricular Myocardial Remodeling

Background and Aims: Pulmonary Hypertension (PH) represents an aetiologically and clinically heterogeneous disorder accompanied by a severely impaired prognosis. Key steps of PH pathogenesis are vascular and right ventricular myocardial remodelling entailing the re-occurrence of fetal variants of the cell adhesion modulating protein fibronectin (Fn) being virtually absent in healthy adult tissues. These variants are liberated into circulation and are therefore qualified as excellent novel serum biomarkers. Moreover, these molecules might serve as promising therapeutic targets. The current study was aimed at quantifying the serum levels of two functionally important fetal Fn variants (ED-A+ and ED-B+ Fn) in patients suffering from PH due to different aetiologies compared to healthy controls. Methods: Serum levels of ED-A+ and ED-B+ Fn were quantified using novel ELISA protocols established and validated in our group in 80 PH patients and 40 controls. Results were analysed with respect to clinical, laboratory, echocardiographic and functional parameters. Results: Serum levels of ED-A+ Fn (p = 0.001) but not ED-B+ Fn (p = 0.722) were significantly increased in PH patients compared to healthy controls. Thus, the following analyses were performed only for ED-A+ Fn. When dividing PH patients into different aetiological groups according to current ESC guidelines, the increase in ED-A+ Fn in PH patients compared to controls remained significant for group 1 (p = 0.032), 2 (p = 0.007) and 3 (p = 0.001) but not for group 4 (p = 0.156). Correlation analysis revealed a significant relation between ED-A+ Fn and brain natriuretic peptide (BNP) (r = 0.310; p = 0.002), six minutes’ walk test (r = −0.275; p = 0.02) and systolic pulmonary artery pressure (PAPsys) (r = 0.364; p &lt; 0.001). By logistic regression analysis (backward elimination WALD) including a variety of potentially relevant patients’ characteristics, only chronic kidney disease (CKD) (OR: 8.866; CI: 1.779–44.187; p = 0.008), C reactive protein (CRP) (OR: 1.194; CI: 1.011–1.410; p = 0.037) and ED-A+ Fn (OR: 1.045; CI: 1.011–1.080; p = 0.009) could be identified as independent predictors of the presence of PH. Conclusions: Against the background of our results, ED-A+ Fn could serve as a promising novel biomarker of PH with potential value for initial diagnosis and aetiological differentiation. Moreover, it might contribute to more precise risk stratification of PH patients. Beyond that, the future role of ED-A+ Fn as a therapeutic target has to be evaluated in further studies

Metabolomic profiling of patients with high gradient aortic stenosis undergoing transcatheter aortic valve replacement

Aim!#!Aim of our study was to evaluate metabolic changes in patients with aortic stenosis (AS) before and after transcatheter aortic valve replacement (TAVR) and to assess whether this procedure reverses metabolomic alterations.!##!Methods!#!188 plasma metabolites of 30 patients with severe high-gradient aortic valve stenosis (pre-TAVR and 6 weeks post-TAVR) as well as 20 healthy controls (HC) were quantified by liquid chromatography tandem mass spectrometry. Significantly altered metabolites were then correlated to an extensive patient database of clinical parameters at the time of measurement.!##!Results!#!Out of the determined metabolites, 26.6% (n = 50) were significantly altered in patients with AS pre-TAVR compared to HC. In detail, 5/40 acylcarnitines as well as 10/42 amino acids and biogenic amines were mainly increased in AS, whereas 29/90 glycerophospholipids and 6/15 sphingomyelins were mainly reduced. In the post-TAVR group, 10.1% (n = 19) of metabolites showed significant differences when compared to pre-TAVR. Moreover, we found nine metabolites revealing reversible concentration levels. Correlation with clinically important parameters revealed strong correlations between sphingomyelins and cholesterol (r = 0.847), acylcarnitines and brain natriuretic peptide (r = 0.664) and showed correlation of acylcarnitine with an improvement of left ventricular (LV) ejection fraction (r = - 0.513) and phosphatidylcholines with an improvement of LV mass (r = - 0.637).!##!Conclusion!#!Metabolic profiling identified significant and reversible changes in circulating metabolites of patients with AS. The correlation of circulating metabolites with clinical parameters supports the use of these data to identify novel diagnostic as well as prognostic markers for disease screening, pathophysiological studies as well as patient surveillance

Comparison of PCWP and LVEDP Measurements in Patients with Severe Aortic Stenosis Undergoing TAVI—Same Same but Different?

Background: Pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure (LVEDP) are often used as equivalents for determination of pulmonary hypertension (PH). PH is a comorbidity in patients with severe aortic valve stenosis (AS) and associated with limited prognosis. The aim of the study was to examine the role of differentiated classification basis of PCWP and LVEDP in patients planning for transcatheter aortic valve implantation (TAVI). Methods: 284 patients with severe AS completed a combined left (LHC) and right heart catheterization (RHC) as part of a TAVI planning procedure. Patients were categorized twice into subtypes of PH according to 2015 European Society of Cardiology (ESC) guidelines—on the one hand with PCWP and on the other hand with LVEDP as classification basis. PCWP-LVEDP relationships were figured out using Kaplan-Meier curves, linear regressions and Bland-Altman analysis. Results: Regarding 1-year mortality, Kaplan-Meier analyses showed similar curves in spite of different classification bases of PH subtypes according to PCWP or LVEDP with exception of pre-capillary PH subtype. PCWP-LVEDP association in the overall cohort was barely present (R = 0.210, R2 = 0.044). When focusing analysis on PH patients only a slightly increased linear regression was noted compared to the overall cohort (R = 0.220, R2 = 0.048). The strongest regression was observed in patients with creatinine ≥ 132 µmol/L (R = 0.357, R2 = 0.127) and in patients with mitral regurgitation ≥ II° (R = 0.326, R2 = 0.106). Conclusions: In patients with severe AS, there is a weak association between hemodynamic parameters measured by LHC and RHC. RHC measurements alone are not suitable for risk stratification with respect to one-year mortality. If analysis of hemodynamic parameters is necessary in patients with severe AS scheduled for TAVI, measurement results of LHC and RHC should be combined and LVEDP could serve as a helpful indicator for risk assessment

Soluble ST2 as a Potential Biomarker for Risk Assessment of Pulmonary Hypertension in Patients Undergoing TAVR?

Background: Severe aortic valve stenosis (AS) is associated with pulmonary hypertension (PH) and has been shown to limit patient survival. Soluble suppression of tumorigenicity-2 (sST2) is a cardiovascular biomarker that has proven to be an important prognostic marker for survival in patients undergoing transcatheter aortic valve replacement (TAVR). The aim of this study was to assess the importance of the sST2 biomarker for risk stratification in patients with severe AS in presence or absence of PH. Methods: In 260 patients with severe AS undergoing TAVR procedure, sST2 serum level concentrations were analyzed. Right heart catheter measurements were performed in 152 patients, with no PH detection in 43 patients and with PH detection in 109 patients. Correlation analyses according to Spearman, AUROC analyses and Kaplan–Meier curves were calculated. Results: Patients with severe AS and PH showed significantly higher serum sST2 concentrations (p = 0.006). The sST2 cut-off value for non-PH patients regarding 1-year survival yielded 5521.15 pg/mL, whereas the cut-off value of PH patients was at a considerably higher level of 10,268.78 pg/mL. A cut-off value of 6990.12 pg/mL was related with a significant probability of PH presence. Survival curves showed that patients with severe AS and PH not only had higher 1-year mortality, but also that increased levels of sST2 plasma concentration were associated with earlier death. Conclusion: sST2 definitely has the potential to provide information about the presence of PH in patients with severe AS, in a noninvasive way

No impact of weather conditions on the outcome of intensive care unit patients

Global warming leads to increased exposure of humankind to meteorological variation, including short-term weather changes. Weather conditions involve changes in temperature, heat and cold, in air pressure and in air humidity. Every single condition influences the incidence and mortality of different diseases such as myocardial infarction and stroke. This study investigated the impact of weather conditions on short- and long-term mortality of 4321 critically ill patients (66 ± 14 years, 2638 men) admitted to an intensive care unit (ICU) over a period of 5 years. Meteorological information (air temperature, air pressure and humidity) for the same period was retrieved. The influence of absolute weather parameters, different seasons, sudden weather changes including 'warm' and 'cold' spells on ICU and long-term mortality was analyzed. After correction for Simplified Acute Physiology Score (SAPS-2), no impact of meteorological conditions on mortality was found. Different seasons, sudden weather changes, 'warm spells' or 'cold spells' did not affect the outcome of critically ill patients