Search

Copyright of Der Kardiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Biomarkers that reflect hemodynamic stress, inflammation, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction may improve risk stratification and add valuable pathobiological insight in patients with out-of-hospital cardiac arrest (OHCA). In total, 120 patients with OHCA who survived at least 48 h after return of spontaneous circulation were consecutively included in the present analysis. Concentrations of 30 biomarkers were measured simultaneously using a multi-panel biomarker assay. Cox regression models were adjusted for age, sex, estimated glomerular filtration rate, lactate concentration, bystander resuscitation, initial cardiac rhythm, and type of targeted temperature management. Overall, 57 patients (47.5%) had a favorable neurological outcome (Cerebral Performance Category ≤ 2) at 30 days, while palliative care was initiated in 49 patients (40.8%), and 52 patients (43.3%) died. After correction for multiple testing with Bonferroni-Holm, 8 biomarkers (including Angiopoietin-2, Procalcitonin, Resistin, IL-4Rα, MMP-8, TNFα, Renin, and IL-1α) were significantly associated with all-cause death. After multivariable adjustment, only angiopoietin-2 (Adjusted (Adj) hazard ratio (HR) per 1-unit increase in standardized biomarker concentrations 1.52 (95% CI 1.16–1.99)) and renin (Adj HR 1.32 (95% CI 1.06–1.65) remained independently associated with an increased risk of death. The discriminatory performance indicated good performance for angiopoietin-2 (area under the curve (AUC): 0.75 (95% CI 0.66–0.75) and was significantly higher (P = 0.011) as compared with renin (AUC: 0.60, 95% CI 0.50–0.60). In conclusion, angiopoietin-2 was significantly associated with all-cause mortality in patients with OHCA who survived the first 48 h and may prove to be useful for risk stratification of these patients. [ABSTRACT FROM AUTHOR]

Background: In patients with pulmonary arterial hypertension, the 6-Minute Walk Test (6MWT) is recommended for risk stratification and follow-up by all guidelines. However, the prognostic value of the 6MWT has been discussed controversially. We sought to compare and validate all published 6MWT cut-off points.Methods: From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)—registry we identified 2391 patients with pulmonary arterial hypertension who had at least one documented 6MWT measurement. A Medline search identified a total of 21 different threshold values for either single-point or change of 6MWT. All values were tested individually for prognostication of 1-year, 2-year and 3-year all-cause mortality.Results: The highest positive likelihood ratio was a cut-off value < 165 ms, whereas the best negative likelihood ratio was found to be a threshold of 440 ms. Furthermore, improvement in 6MWT had considerably less predictive value on mortality and survival than deterioration. Moreover, absolute single-point values outperformed change values for both improvement and worsening.Conclusion: Our data confirmed the prognostic relevance of the 6MWT and support the cut-off values stated in most recent guidelines. Furthermore, these results explain why changes in 6MWT did not correlate consistently with prognosis in previous studies. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of right ventricular long axis strain (RV-LAS), a parameter of longitudinal function, with outcome in patients with non-ischaemic dilated cardiomyopathy (NIDCM).Methods: In 441 patients with NIDCM, RV-LAS was analysed retrospectively by measuring the length between the epicardial border of the left ventricular apex and the middle of a line connecting the origins of the tricuspidal valve leaflets in end-diastole and end-systole on non-contrast standard cine sequences.Results: The primary endpoint (cardiac death or heart transplantation) occurred in 41 patients, whereas 95 reached the combined endpoint (including cardiac decompensation and sustained ventricular arrhythmias) during a median follow-up of 4.2 years. Kaplan-Meier survival curves showed a poor outcome in patients with RV-LAS values below -10% (log-rank, p < 0.0001). In a risk stratification model RV-LAS improved prediction of outcome in addition to RV ejection fraction (RVEF) and presence of late gadolinium enhancement. Assessment of RV-LAS offered incremental information compared to clinical symptoms, biomarkers and RVEF. Even in the subgroup with normal RVEF (>45%, n = 213) reduced RV-LAS was still associated with poor outcome.Conclusion: Assessment of RV-LAS is an independent indicator of outcome in patients with NIDCM and offers incremental information beyond clinical and cardiac MR parameters.Key Points: • Impaired right ventricular longitudinal function (RV-LAS) is associated with poorer cardiac outcomes. • Poor outcome is associated with decreased RV-LAS even in patients with RVEF >45%. • Addition of RV-LAS to known risk factors enhances the power prognostic information. [ABSTRACT FROM AUTHOR]

Introduction: Delivery of crushed ticagrelor via a nasogastric tube is a widely spread off-label use in unconscious patients following out-of-hospital cardiac arrest (OHCA). Notwithstanding the importance of a potent dual antiplatelet therapy in these patients, the efficacy of crushed ticagrelor after OHCA has not been established yet. Methods: In a prospective, single-center, observational trial, 38 consecutive MI patients after OHCA were included. 27 patients (71.1 %) underwent mild induced hypothermia. The primary outcome was platelet inhibition at 24h measured by impedance aggregometry. Results: There was sufficient platelet inhibition in most patients after OHCA. In all hypothermic patients, there was an adequate platelet inhibition by ticagrelor at 24 h ( p < 0.001). 15 patients (39.5 %) had significant gastroesophageal reflux and one patient with significant reflux had inadequate platelet inhibition at 24 h. There were no stent thrombosis or recurrent atherothrombotic events in these patients. Conclusion: Administration of crushed ticagrelor via a nasogastric tube reliably inhibited platelet function in vitro and in vivo regardless of the presence of hypothermia in MI patients. Thus, platelet inhibition can be reliably achieved in MI patients during neuroprotective hypothermia following OHCA. [ABSTRACT FROM AUTHOR]

Soluble TWEAK is a member of the TNF-alpha family of cytokines that has been shown to predict mortality in patients with heart failure. Pulmonary artery hypertension is a devastating disease, in which right ventricular function has been shown to be the major determinant of prognosis. In this hypothesis-generating study, we sought to evaluate the potential usefulness of sTWEAK in the prediction of disease severity in patients with pulmonary artery hypertension. We therefore conducted a retrospective analysis of sTWEAK serum levels in 95 stable patients with PAH. For all patients data on hemodynamic parameters, biomarkers and functional exercise tests were available. Compared to controls, patients with PAH showed significantly decreased levels of sTWEAK [median 314 pg/ml (interquartile range 217-473 pg/ml) vs. 405 (321-496 pg/ml); PAH vs. controls; P < 0.0001]. Soluble TWEAK levels were inversely correlated with NYHA class, pulmonary artery pressure, pulmonary vascular resistance, NT-proBNP, and troponin T levels and directly correlated with cardiac index, reduced 6-min walk test distances, and peak oxygen consumption. ROC curve analysis of sTWEAK levels in PAH patients revealed a cutoff value of 306 pg/ml for sTWEAK to be predictive of a reduced exercise capacity (6-min walk test <300 m) in patients with PAH with a similar predictive value compared to NT-proBNP. Intraindividual serial evaluation of sTWEAK revealed the potential of sTWEAK as follow-up marker in patients with PAH. In our hypothesis-generating study, sTWEAK was closely correlated to hemodynamic, functional, and serological indices of outcome in patients with PAH. Further prospective studies are needed to determine the role of sTWEAK as potential biomarker in patients with PAH. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension is a severe and progressive disease characterized by a pulmonary vascular remodeling process with expansion of collateral endothelial cells and total vessel occlusion. Endothelial cells are believed to be at the forefront of the disease process. Vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor, VEGF receptor-2 (VEGFR-2), play a central role in angiogenesis, endothelial cell protection, but also in the destabilization of endothelial barrier function. Therefore, we investigated the consequences of altered VEGF signaling in an experimental model, and looked for translational correlates of this observation in patients. We performed an endothelial cell-specific conditional deletion of the kinase insert domain protein receptor (kdr) gene, coding for VEGFR-2, in C57/BL6 mice (Kdr∆end) and held them in an environmental chamber with 10% FiO2 or under normoxia for 6 weeks. Kdr knockout led to a mild PH phenotype under normoxia that worsened under hypoxia. Kdr∆end mice exhibited a significant increase in pulmonary arterial wall thickness, muscularization, and VEGFR-3+ endothelial cells obliterating the pulmonary artery vessel lumen. We observed the same proliferative vasculopathy in our rodent model as seen in patients receiving anti-angiogenic therapy. Serum VEGF-a levels were elevated both in the experimental model and in humans receiving bevacizumab. Interrupted VEGF signaling leads to a pulmonary proliferative arteriopathy in rodents after direct ablative gene manipulation of Kdr. Histologically, similar vascular lesions can be observed in patients receiving anti-VEGF treatment. Our findings illustrate the importance of VEGF signaling for maintenance of pulmonary vascular patency. [ABSTRACT FROM AUTHOR]