Objectives:Renal sympathetic denervation (RDN) reduces blood pressure (BP). However, one out of three patients does not exhibit a significant BP response to the therapy. This study investigates the... Show moreObjectives:Renal sympathetic denervation (RDN) reduces blood pressure (BP). However, one out of three patients does not exhibit a significant BP response to the therapy. This study investigates the association between noninvasive vascular stiffness indices and RDN-mediated BP reduction.Methods:In this prospective, single-arm pilot study, patients with systolic office BP at least 140 mmHg, mean 24-h systolic ambulatory blood pressure (ABP) at least 130 mmHg and at least three prescribed antihypertensive drugs underwent radiofrequency RDN. The primary efficacy endpoint was temporal evolution of mean 24-h systolic ABP throughout 1-year post RDN (measured at baseline and 3-6-12 months). Effect modification was studied for baseline ultrasound carotid-femoral and magnetic resonance (MR) pulse wave velocity (PWV), MR aortic distensibility, cardiac MR left ventricular parameters and clinical variables. Statistical analyses were performed using linear mixed-effects models, and effect modification was assessed using interaction terms.Results:Thirty patients (mean age 62.5 +/- 10.7 years, 50% women) with mean 24-h ABP 146.7/80.8 +/- 13.7/12.0 mmHg were enrolled. Following RDN, mean 24-h systolic ABP changed with -8.4 (95% CI: -14.5 to -2.3) mmHg/year (P = 0.007). Independent effect modifiers were CF-PWV [+2.7 (0.3 to 5.1) mmHg/year change in outcome for every m/s increase in CF-PWV; P = 0.03], daytime diastolic ABP [-0.4 (-0.8 to 0.0) mmHg/year per mmHg; P = 0.03], age [+0.6 (0.2 to 1.0) mmHg/year per year of age; P = 0.006], female sex [-14.0 (-23.1 to -5.0) mmHg/year as compared with men; P = 0.003] and BMI [+1.2 (0.1 to 2.2) mmHg/year per kg/m(2); P = 0.04].Conclusion:Higher CF-PWV at baseline was associated with a smaller reduction in systolic ABP following RDN. These findings could contribute to improve identification of RDN responders. Show less
Zandvoort, L.J.C. van; Otsuka, K.; Villiger, M.; Neleman, T.; Dijkstra, J.; Zijlstra, F.; ... ; Daemen, J. 2021
Background: Intravascular polarization-sensitive optical frequency domain imaging (PS-OFDI) offers a novel approach to measure tissue birefringence, which is elevated in collagen and smooth muscle... Show moreBackground: Intravascular polarization-sensitive optical frequency domain imaging (PS-OFDI) offers a novel approach to measure tissue birefringence, which is elevated in collagen and smooth muscle cells, that in turn plays a critical role in healing coronary thrombus (HCT). This study aimed to quantitatively assess polarization properties of coronary fresh and organizing thrombus with PS-OFDI in patients with acute coronary syndrome (ACS).Methods and Results:The POLARIS-I prospective registry enrolled 32 patients with ACS. Pre-procedural PS-OFDI pullbacks using conventional imaging catheters revealed 26 thrombus-regions in 21 patients. Thrombus was manually delineated in conventional OFDI cross-sections separated by 0.5 mm and categorized into fresh thrombus caused by plaque rupture, stent thrombosis, or erosion in 18 thrombus-regions (182 frames) or into HCT for 8 thrombus-regions (141 frames). Birefringence of coronary thrombus was compared between the 2 categories. Birefringence in HCTs was significantly higher than in fresh thrombus (Delta n=0.47 (0.37-0.72) vs. Delta n=0.25 (0.17-0.29), P=0.007). In a subgroup analysis, when only using thrombus-regions from culprit lesions, ischemic time was a significant predictor for birefringence (ss (Delta n)=0.001 per hour, 95% CI [0.0002-0.002], P=0.023).Conclusions: Intravascular PS-OFDI offers the opportunity to quantitatively assess the polarimetric properties of fresh and organizing coronary thrombus, providing new insights into vascular healing and plaque stability. Show less
Jansen, J.C.; Hoek, B. van; Metselaar, H.J.; Berg, A.P. van den; Zijlstra, F.; Huijben, K.; ... ; Lefeber, D.J. 2020
Congenital disorders of glycosylation (CDG) are a rapidly expanding group of rare genetic defects in glycosylation. In a novel CDG subgroup of vacuolar-ATPase (V-ATPase) assembly defects, various... Show moreCongenital disorders of glycosylation (CDG) are a rapidly expanding group of rare genetic defects in glycosylation. In a novel CDG subgroup of vacuolar-ATPase (V-ATPase) assembly defects, various degrees of hepatic injury have been described, including end-stage liver disease. However, the CDG diagnostic workflow can be complex as liver disease per se may be associated with abnormal glycosylation. Therefore, we collected serum samples of patients with a wide range of liver pathology to study the performance and yield of two CDG screening methods. Our aim was to identify glycosylation patterns that could help to differentiate between primary and secondary glycosylation defects in liver disease. To this end, we analyzed serum samples of 1042 adult liver disease patients. This cohort consisted of 567 liver transplant candidates and 475 chronic liver disease patients. Our workflow consisted of screening for abnormal glycosylation by transferrin isoelectric focusing (tIEF), followed by in-depth analysis of the abnormal samples with quadruple time-of-flight mass spectrometry (QTOF-MS). Screening with tIEF resulted in identification of 247 (26%) abnormal samples. QTOF-MS analysis of 110 of those did not reveal glycosylation abnormalities comparable with those seen in V-ATPase assembly factor defects. However, two patients presented with isolated sialylation deficiency. Fucosylation was significantly increased in liver transplant candidates compared to healthy controls and patients with chronic liver disease. In conclusion, a significant percentage of patients with liver disease presented with abnormal CDG screening results. However, the glycosylation pattern was not indicative for a V-ATPase assembly factor defect. Advanced glycoanalytical techniques assist in the dissection of secondary and primary glycosylation defects. Show less
OBJECTIVES The purpose of this study was to derive a biomechanical stress metric that was based on the multifactorial assessment of coronary plaque morphology, likely related to the propensity of... Show moreOBJECTIVES The purpose of this study was to derive a biomechanical stress metric that was based on the multifactorial assessment of coronary plaque morphology, likely related to the propensity of plaque rupture in patients.BACKGROUND Plaque rupture, the most frequent cause of coronary thrombosis, occurs at locations of elevated tensile stress in necrotic core fibroatheromas (NCFAs). Finite element modeling (FEM), typically used to calculate tensile stress, is computationally intensive and impractical as a clinical tool for locating rupture-prone plaques. This study derived a multifactorial stress equation (MSE) that accurately computes peak stress in NCFAs by combining the influence of several morphological parameters.METHODS Intravascular ultrasound and optical frequency domain imaging were conducted in 30 patients, and plaque morphological parameters were defined in 61 NCFAs. Multivariate regression analysis was applied to derive the MSE and compute a peak stress metric (PSM) that was based on the analysis of plaque morphological parameters. The accuracy of the MSE was determined by comparing PSM with FEM-derived peak stress values. The ability of the PSM in locating plaque rupture sites was tested in 3 additional patients.RESULTS The following parameters were found to be independently associated with peak stress: fibrous cap thickness (p < 0.0001), necrotic core angle (p = 0.024), necrotic core thickness (p < 0.0001), lumen area (p < 0.0001), necrotic core including calcium areas (p = 0.017), and plaque area (p = 0.003). The PSM showed excellent correlation (R = 0.85; p < 0.0001) with FEM-derived peak stress, thus confirming the accuracy of the MSE. In only 56% (n = 34) of plaques, the thinnest fibrous cap thickness was a determining parameter in identifying the cross section with highest PSM. In coronary segments with plaque ruptures, the MSE precisely located the rupture site.CONCLUSIONS The MSE shows potential to calculate the PSM in coronary lesions rapidly. However, further studies are warranted to investigate the use of biomechanical stress profiling for the prognostic evaluation of patients with atherosclerosis. (C) 2020 by the American College of Cardiology Foundation. Show less
Villiger, M.; Otsuka, K.; Karanasos, A.; Doradla, P.; Ren, J.; Lippok, N.; ... ; Bouma, B.E. 2018
Cardioprotective effects of erythropoietin (EPO) have been shown in experimental and smaller clinical studies. We performed a prospective, multicentre, randomized trial to assess the effects of a... Show moreCardioprotective effects of erythropoietin (EPO) have been shown in experimental and smaller clinical studies. We performed a prospective, multicentre, randomized trial to assess the effects of a single high dose of EPO after primary coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI). Patients with a successful PCI for a first STEMI were randomized to receive either standard medical care alone, or in combination with a single bolus with 60 000IU i.v. of epoetin alfa within 3 h after PCI. Primary endpoint was left ventricular ejection fraction (LVEF) after 6 weeks, assessed by planar radionuclide ventriculography. Pre-specified secondary endpoints included enzymatic infarct size and major adverse cardiovascular events. A total of 529 patients were enrolled (EPO n = 263, control n = 266). At baseline (before EPO administration), groups were well-matched for all relevant characteristics. After a mean of 6.5 (+/- 2.0) weeks, LVEF was 0.53 (+/- 0.10) in the EPO group and 0.52 (+/- 0.11) in the control group (P = 0.41). Median area under the curve (inter-quartile range) after 72 h for creatinine kinase was 50 136 (28 212-76 664)U/L per 72 h in the EPO group and 53 510 (33 973-90 486)U/L per 72 h in the control group (P = 0.058). More major adverse cardiac events occurred in the control than in the EPO group (19 vs. 8; P = 0.032). A single high dose of EPO after a successful PCI for a STEMI did not improve LVEF after 6 weeks. However, the use of EPO was related to less major adverse cardiovascular events and a favourable clinical safety profile. Clinical Trial Registration Information:NCT00449488;http://www.clinicaltrials.gov/ct2/show/NCT00449488?term=voors&rank=2 Show less
