Degenerative aortic stenosis (AS) is the most frequent form of acquired valvular heart disease. AS is known to entail endothelial dysfunction caused by increased mechanical shear stress leading to ...elevated circulatory levels of microparticles. Endothelial and platelet microparticles (EMP and PMP) are small vesicles that originate from activated cells and thrombocytes. We sought to evaluate whether transcatheter aortic valve implantation (TAVI) procedure would elicit effects on circulating EMP and PMP. 92 patients undergoing TAVI procedure for severe AS were included in this study. Samples were obtained at each visit before TAVI, 1 week post-procedure and at 1, 3 and after 6 months after TAVI and were evaluated using flow cytometry. A 12 month clinical follow-up was also performed. CD62E+ EMP concentration before TAVI was 21.11 % (±6.6 % SD) and declined to 20.99 % (±6.8 % SD) after 1 week, to 16.63 % (±5.4 % SD,
p
< 0.0001) after 1 month, to 17.08 % (±4.6 % SD,
p
< 0.0001) after 3 months and to 15.94 % (±5.4 % SD,
p
< 0.0001) after 6 months. CD31+/CD42b−, CD31+/Annexin+/− EMP remained unchanged. CD31+/CD41b+ PMP evidenced a slight, but statistically significant increase after TAVI and remained elevated during the entire follow-up. Apart from a procedure-related improvement in echocardiographic parameters, TAVI procedure led also to a decline in CD62E+ EMP. The reduction in pressure gradients with less hemodynamic shear stress seems also to have beneficially affected endothelial homeostasis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims
Acutely decompensated heart failure (ADHF) leads to neurohumoral activation potentially affecting vascular tone and organ perfusion and may be linked to unfavourable outcome. Global ...haemodynamic, clinical, and laboratory parameters may severely underestimate tissue hypoperfusion. Therefore, the purpose of this study was to evaluate microvascular flow index (MFI) in patients with ADHF and to assess the effect of standard pharmacological therapy using Sidestream Dark Field (SDF) imaging.
Methods and results
Twenty-seven patients (mean age 75.5 ± 10.1 years, 48% male) with ADHF in New York Heart Association functional class ≥III were included. Serum markers of neurohumoral activation brain natriuretic peptide (BNP), endothelin-1 (ET-1), noradrenaline (NA), and echocardiographic parameters of left ventricle-function were determined at hospital admission and the day before discharge. Using SDF imaging, MFI was evaluated at both time-points in semi-quantitative vessel categories (small: 10-25 μm; medium: 26-50 μm; and large: 51-100 μm). At admission, increased serum levels of BNP, NA, and ET-1 and a severely reduced MFI were observed in association with ADHF. Serum levels of BNP, NA, and ET-1 decreased significantly with standard pharmacological therapy (BNP: 2163 ± 1577 vs.1006 ± 945 pg/mL, P< 0.05; NA: 349 ± 280 to 318 ± 265 pg/mL, P< 0.05; ET-1: 5.08 ± 0.72 to 4.81 ± 0.59 pg/mL; P< 0.01). Standard pharmacological treatment also had a profound impact on tissue perfusion by significantly improving median MFI in small 2.6; inter-quartile range (IQR) 2.3-2.9 vs. 2.9; IQR 2.8-3.0; P= 0.01) and medium-sized (2.0; IQR 1.9-2.5 vs. 2.7; IQR 2.5-2.8; P< 0.01) vessels.
Conclusion
In patients with ADHF, microvascular tissue perfusion is impaired even when global haemodynamic or laboratory signs of hypoperfusion are absent. Effective pharmacological treatment to decrease neurohumoral activation significantly improves microflow. Hypoperfusion in ADHF is potentially linked to neurohumoral activation with increased plasma levels of vasoconstrictors and sympatho-adrenergic activity.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Hypoxia frequently associated with certain physiologic and pathologic conditions influences numerous cellular functions. Because the effects of short-term hypoxia are incompletely understood, we ...examined phagocytosis and cytokine production as well as the activation of the transcription factors HIF-1 and NFκB in peripheral blood cells of healthy volunteers exposed to an oxygen concentration equivalent to that found at a height of 5500 m. Furthermore, we analysed plasma HIF-1 and serum concentrations of various HIF-1-dependent genes. Results showed that short-term hypoxia increased phagocytosis in neutrophils without affecting monocyte phagocytosis. Hypoxia decreased basal TNFα concentration in monocytes and basal interferon γ concentration in CD4+ T lymphocytes. In contrast, plasma HIF and serum VEGF concentrations were not affected by hypoxia, although serum EPO concentration was raised. In PBMC, hypoxia increased cytosolic HIF-1 concentration without affecting nuclear HIF-1 concentration and led to a rise in the nuclear NFκB in PBMC. Our results show that short-term hypoxia affects immune functions in healthy individuals. Furthermore, we speculate that the effects of hypoxia are not due to HIF-1, but are caused by the activation of NFκB .
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
A 75-year-old man with a history of aortic valve repair and Dacron graft (28 mm) replacement of the ascending aorta 8 years earlier (David procedure) sought treatment for recurrent severe aortic ...regurgitation (A).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Percutaneous coronary interventions (PCI) with drug-coated balloons (DCB) might be a promising trade-off between balloon angioplasty and drug-eluting stents, since DCB inhibit neointimal ...proliferation and limit duration of dual antiplatelet therapy. We investigated the safety, feasibility, and 6-month results of fractional flow reserve (FFR)-guided use of the paclitaxel-coated SeQuent Please
®
balloon without stenting for elective PCI of de novo lesions.
Methods and results
In 46 patients (54 lesions) with stable symptomatic coronary artery disease (CAD), a FFR-guided POBA (plain old balloon angioplasty) was performed. In case of a sufficient POBA result with residual stenosis < 40 %, FFR > 0.8 and no severe dissection, the target lesion was finally dilated using the DCB. Quantitative coronary angiography (QCA) was performed before and after the index procedure and at 6-month follow-up (f/u) to calculate late lumen loss (LLL) and net luminal gain (NLG). Optical coherence tomography (OCT) was performed at f/u to assess vascular remodeling. DCB-only treatment was applied to 43 patients (51 lesions), while 3 patients (3 lesions) needed provisional stenting. Invasive f/u was completed in 39 patients (47 lesions). At the stenotic site, the lumen diameter showed a trend toward progressive increase at f/u (LLL: −0.13 ± 0.44 mm, n.s.; NLG: 1.10 ± 0.53 mm,
p
< 0.001) without aneurysm formation or restenosis after DCB-only treatment.
Conclusions
FFR-guided DCB-only PCI of de novo lesions appeared feasible and safe in stable CAD with clopidogrel discontinuation after 4 weeks, showing a trend toward positive vessel remodeling without lumen loss at 6 months.
Clinical trial registration
http://www.clinicaltrials.gov
. Unique identifier: NCT02120859
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Indications for prophylactic implantable cardioverter-defibrillator implantation in patients with nonischemic dilated cardiomyopathy (DCM) are based on left ventricular (LV) ejection fraction (LVEF), ...although LVEF has limited ability to predict arrhythmias. It has recently been shown that strain echocardiography can predict ventricular arrhythmias in patients after myocardial infarction. The aim of this study was to evaluate whether strain echocardiography may help in the risk stratification of ventricular arrhythmias in patients with DCM.
Ninety-four patients with nonischemic DCM were prospectively included. By speckle-tracking strain echocardiography, global longitudinal strain was calculated as the average of peak longitudinal strain from a 16-segment LV model. The time interval from electrocardiographic peak R to peak negative strain was assessed in each LV segment. Mechanical dispersion was defined as the standard deviation of time to peak negative strain from 16 LV segments.
After a median of 22 months of follow-up (range, 1-46 months), 12 patients (13%) had experienced arrhythmic events, defined as sustained ventricular tachycardia or cardiac arrest. LVEF and global longitudinal strain were reduced in patients with DCM with arrhythmic events compared with those without (28 ± 10% vs 38 ± 13%, P = .01, and -6.4 ± 3.3% vs -12.3 ± 5.2%, P < .001, respectively). Global longitudinal strain showed greater area under the curve than LVEF to identify arrhythmic events in receiver operating characteristic curve analyses (P = .05). Patients with arrhythmic events had increased mechanical dispersion (98 ± 43 vs 56 ± 18 ms, P < .001). Mechanical dispersion predicted arrhythmias independently of LVEF (hazard ratio, 1.28; 95% confidence interval, 1.11-1.49; P = .001).
Global longitudinal strain is a promising marker of arrhythmias. Mechanical dispersion predicted arrhythmic events in patients with DCM independently of LVEF. Strain echocardiography may help in the risk stratification of patients with DCM not fulfilling current implantable cardioverter-defibrillator indications.
Sepsis is one of the most prevalent life-threatening conditions in the intensive care unit. Patients suffer from impaired organ function, reduced physical functional capacity and decreased quality of ...life even after surviving sepsis. The identification of prognostic factors for the medium-term and long-term outcomes of this condition is necessary to develop personalised theragnostic approaches. Sepsis can cause cardiac impairment. The impact of this septic cardiomyopathy on patient's long-term outcome remains unclear. This study aims to evaluate cardiovascular risk factors, particularly the occurrence of septic cardiomyopathy, regarding their suitability as prognostic factors for the short-term and long-term outcomes of septic patients. Additionally, the study seeks to validate preclinical pathophysiological findings of septic cardiomyopathy in the clinical setting.
In this prospective monocentric cohort study, patients will be clinically assessed during the acute and postacute phase of sepsis and two follow-ups after 6 and 12 months. To determine the effect of septic cardiomyopathy and concomitant cellular and molecular changes on patient mortality and morbidity, a comprehensive cardiovascular and molecular deep phenotyping of patients will be performed. This includes an echocardiographic and electrocardiographic assessment, and the evaluation of heart rate variability, body composition, mitochondrial oxygen metabolism, macrocirculation and microcirculation, and endothelial barrier function. These analyses are complemented by routine immunological, haematological and biochemical laboratory tests and analyses of the serum metabolome and lipidome, microbiome and epigenetic modifications of immune cells. The reversibility of patients' organ dysfunction, their quality of life and physical functional capacity will be investigated in the follow-ups. Patients with cardiomyopathy without infection and healthy subjects will serve as control groups.
Approval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (5276-09/17). The results will be published in peer-reviewed journals and presented at appropriate conferences.
DRKS00013347; NCT03620409.
Background
Rapid ventricular pacing (RVP) is an established technique to temporarily reduce left ventricular output during transcatheter aortic valve implantation (TAVI). The purpose of this study ...was to evaluate the impact of RVP on microvascular tissue perfusion (MTP) in patients undergoing TAVI.
Methods and results
We studied 42 patients (mean age 81.8 ± 6.9 years,
n
= 18 females. EuroSCORE 33 ± 12 %) during TAVI. MTP was analyzed using Sidestream–Darkfield imaging, of the sublingual microvasculature. Microvascular flow index (MFI) was continuously measured in small (10–25 μm)- and medium (26–50 μm)-sized vessels, starting 10 s before and ending 12 s after RVP. Further, perfused capillary density, total vessel density and the proportion of perfused vessels were assessed. After a mean RVP duration of 14.3 s (range 6–29), mean arterial pressure decreased from 68 ± 05 to 40 ± 7 mmHg (
p
< 0.001). This was associated with a significant decrease of MFI in small- and medium-sized vessels from 2.29 ± 0.64 and 2.36 ± 0.6 to 0.87 ± 0.66 (
p
< 0.001) and 1.0 ± 0.83 (
p
< 0.001), respectively. MFI remained significantly below baseline values (small: 1.75 ± 0.8,
p
= 0.001 vs. baseline; medium: 1.77 ± 0.85;
p
= 0.005 vs. baseline) at 12 s after end of RVP.
Conclusions
The study demonstrates a time-dependent effect of RVP on microflow, leading to 50 and 25 % of baseline at 8 and 18 s of RVP, respectively. In a substantial proportion of patients, RVP is associated with microcirculatory arrest and a delayed recovery of microflow. Although the impact of these findings on outcome is yet unclear, TAVI operators should be aware of the potentially adverse effects of even short periods of RVP.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival ...and symptomatic outcomes of patients in relation to residual TR after T-TEER.
Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm
). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012).
T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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