Circulating endothelial cells: Prognostic value in patients with glioblastoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13517-e13517
Author(s):  
María Ángeles Vaz Salgado ◽  
Julie Earl ◽  
Victor Rodriguez Berrocal ◽  
Freddy Salge ◽  
Ana Gomez ◽  
...  

e13517 Background: Glioblastoma (GB) is an aggressive tumor. Circulating Endothelial Cells (CECs) can be detected in peripheral blood and have been related to angiogenesis. CECs have an unclear prognostic value in patients with glioblastoma. The objective of this study was to quantify the presence and number of CECs in GB patients and determine its potential prognostic role. Methods: In this prospective, single center study, peripheral blood samples were obtained at the time of GB diagnosis. For the detection of CECs, 4 ml of blood was analyzed using the CellSearch system (Veridex). CEC blood samples were classified as CD146+, CD105+, CD45− and DAPI+. CEC detection was performed prior to surgery in a total of 26 patients and 22 patients with glioblastoma were included in the final analysis. We mesured progression free survival (PFS) and overall survival (OS). Results: Between 2014 and 2016, twenty two patients with histologically confirmed glioblastoma were studied. There were 14 males and 8 females with an average age of 63 years (range 42-81). A complete resection was achieved in 50% of cases, partial or subtotal resection in 31.8% and biopsy in 18%. The mean number of CECs was 59.3 cells/mL (range 0-954). Patients were classified into two groups depending on the number of CECs: group 1 had a CEC count below the mean and group 2 had a CEC count above the mean. A total of 17 patients (77.2%) were in group 1 and 5 patients (22.7%) were in group 2.The median OS was 14.4 months (range -0.36-33.36) for the entire study population. The median OS was 17.4 months (IC95% 11.47-23.37) for patients in group 1 and 8.12 months for patients in group 2 (IC 95% 4.38-11.85) p = 0.002. The median PFS was 8.94 m (IC95% 5.1-12.69) for group 1 and 3.95 for group 2 (IC 95% 2.91-4.98) p = 0.097. Conclusions: CECs can be detected in recently diagnosed GB patients. The present study demonstrates a possible prognostic value for CEC determination in GB cases at the time of diagnosis.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 441.1-441
Author(s):  
F. Pignataro ◽  
L. Zorzino ◽  
W. Maglione ◽  
A. Minniti ◽  
G. Clericuzio ◽  
...  

Background:Endothelial damage and fibroproliferative vasculopathy of small vessels are pathological hallmarks of Systemic Sclerosis (SSc). Detection and analysis of circulating endothelial cells (CECs) detached from affected blood vessels may be an informative tool to study vascular dysfunction and could be considered a novel biomarker of scleroderma vasculopathy. Our group first showed the presence of CECs in SSc by fluorescence-activated cell sorting (FACS), demonstrating that a raised counts of active CECs may represent direct evidence of active vascular disease in SSc. Despite these interesting data, issues related to difficulties in CEC counting through FACS analysis, due their very low concentration in peripheral blood, prevented further investigations in this field. Recently, a specific kit for the detection of CECs has been developed through the CellSearch System (CS), a semi-automated device for the standardized analysis of rare cells, such as CECs, in peripheral blood.Objectives:To assess the counts of CECs determined by the CS in SSc patients and to evaluate their clinical implication and potential as vascular biomarker in SSc.Methods:10mL of blood samples were collected from 29 subjects (19 SSc patients and 10 healthy donors - HDs) and stored in tubes containing a specific preservative, to allow the analysis of 4mL of blood within 72 hours, according to manufacturer instructions. Out of 19 SSc patients, 18 were female, 10 had the limited form and 9 the diffuse cutaneous variant of SSc. CS uses a proprietary kit containing a ferrofluid-based reagent, that target CD146 to magnetically capture CECs, and the immunofluorescent reagents to stain the CECs, defined as CD146+, CD105-PE+, DAPI+ and CD45-APC-. Clinical, laboratoristic and demographic data were also collected.Results:The mean number of CECs in patients with SSc was significantly higher in comparison to HDs (554/4mL vs. 53.5/4 mL, p=0.0042). When analyzed according to disease subset, both lcSSc and dcSSc showed significantly increased levels of CECs in comparison with HDs (p=0.003 and p=0.005, respectively). No statistical difference was observed in the mean number of CECs in patients with lcSSc compared to those with dcSSc. Regarding vascular involvement, the CECs counts strictly correlated with the presence of digital ulcers (DUs) (p=0.0001) showing a median of 863cells/4mL for the SSc patients with DUs versus a median of 276.2/4mL for the SSc patients without DUs. No statistical correlation was found between CECs and serological autoantibody pattern, skin parameters, or joint and muscle involvement. Patients with active disease, according to the EUSTAR Activity Index, showed a higher CECs value than those with inactive disease (p=0.0012).Conclusion:The amount of CECs detectable in peripheral blood has been recently proposed as a marker of endothelial damage in different vascular diseases, including SSc. However, currently no standardized method is available to determine CEC counts, which makes reported data on CECs reliable and suitable. The CS system is a commercially available semi-automated system that enables standardized determination of CECs. Thus, we examined clinical utility of CECs count by this system in SSc patients. Our results confirm that baseline CEC counts, evaluated by a new standardized method, may represent direct evidence of endothelial damage in SSc and could be a promising tool for monitoring active disease and evaluating therapeutic responses to vascular and immunosuppressive treatments.References:[1]Del Papa N, Pignataro F. Front Immunol. 2018 Jun 18;9:1383[2]De Simone C et al. J Eur Acad Dermatol Venereol. 2014 May;28(5):590-6[3]Del Papa N et al. Arthritis Rheum. 2004 Apr;50(4):1296-304Disclosure of Interests:Francesca Pignataro: None declared, Laura Zorzino: None declared, Wanda Maglione: None declared, Antonina Minniti: None declared, Giulia Clericuzio: None declared, Marco Picozzi: None declared, Cecilia Simonelli Employee of: Menarini Silicon Biosystems, Francesco Picardo Employee of: Menarini Silicon Biosystems, Roberto Caporali: None declared, Nicoletta Del Papa: None declared


2011 ◽  
Vol 30 (10) ◽  
pp. 1644-1648 ◽  
Author(s):  
Vefik Arica ◽  
Murat Tutanc ◽  
Oktay Hasan Ozturk ◽  
Secil Arica ◽  
Fatmagul Basarslan ◽  
...  

Aim: In the study, we examined erdosteine’s effects on platelet functions and coagulation. Materials and methods: A total 29 young albino Wistar rats were divided into four groups. Control rats ( n = 6) were given saline; Group 1 rats ( n = 7) were given 3 mg/kg erdosteine by oral gavage for 3 days; Group 2 rats ( n = 7) were given 10 mg/kg erdosteine by oral gavage for 3 days; and Group 3 rats ( n = 9) were given 30 mg/kg erdosteine for 3 days. Twenty-four hours after the final dose, blood samples were drawn from a portal vein. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR) were measured, and platelet counts were examined in a peripheral blood smear by light microscopy. Results: PT and INR values of Group 1 increased compared to the controls but did not change in Group 3. Hemostatic parameters were not measured in Group 2 because the blood samples in Group 2’s tubes clotted rapidly. Platelet counts of the peripheral blood from Group 2 were low but were normal in other groups. Conclusion: We have concluded erdosteine may disrupt hemostasis parameters by its different metabolites in patients. Erdosteine has dual effects on hemostasis via its different metabolites, which occur in different doses.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 850-850
Author(s):  
Mark A Fiala ◽  
Soo Park ◽  
Camille N. Abboud ◽  
Amanda F. Cashen ◽  
Meagan Jacoby ◽  
...  

Abstract Background: The need to repeat peripheral blood stem cell (PBSC) mobilization and collection arises infrequently in healthy donors, but may be required due to insufficient initial collection, graft failure, or relapse of the recipient’s disease. Currently no published data exists on the efficacy of remobilization of healthy PBSC donors. Studies of remobilization in patients undergoing autologous transplantation (ASCT) have largely focused on the use of alternative mobilization agents such as chemotherapy or plerixafor. Boeve et al (Bone Marrow Transplant, 2004) reported that remobilization with G-CSF in patients undergoing ASCT who failed initial mobilization with G-CSF, resulted in higher numbers of CD34+ cells collected than the initial collection, though this required a doubling of the dose of G-CSF. Patients/Methods: We performed retrospective chart review of 977 consecutive adult (>18 yrs) donors who underwent apheresis for PBSC donation at Washington University School of Medicine from 1995 through 2013. We identified 66 donors who had undergone more than one mobilization. Two cohorts of donors were identified for analysis: Group 1 included donors mobilized initially and again subsequently with G-CSF (10 ug/kg/day), or GM-CSF (5 ug/kg/day) + G-CSF (10 ug/kg/day). Group 2 consisted of donors mobilized with a CXCR4 antagonist, plerixafor (240-320 ug/kg) or POL6326 (1000-2500 ug/kg), and subsequently were remobilized with G-CSF (10 ug/kg/day). Statistical Analysis: Spearman correlations were performed to analyze the relationship between peak peripheral blood (PB) CD34+/uL level; the number of CD34+ cells collected per kg (recipient weight); and the number of CD34+ cells per L of apheresis collected during initial mobilization (MOB1) and remobilization (MOB2); and the interval (days) between MOB1 and MOB2. One-way ANOVA with repeated measures analyses were performed to determine the relationship of PB CD34+/uL, CD34+/kg and CD34+/L during MOB1 and MOB2. Results: Group 1 included 30 donors. The median age was 49 years (range 18-75) and 15 were male. The median number of days between MOB1 and MOB2 was 140 (range 26-2238). All 30 donors were remobilized due to graft failure or relapse of the recipient’s disease. PB CD34+/uL, CD34+/kg and CD34+/L all correlated between MOB1 and MOB2. The mean PB CD34/uL at MOB1 was 69 compared to 37 at MOB2 (p= 0.029); the mean CD34/kg collected at MOB1 was 5.6x106 compared to 3.3x106 at MOB2 (p= 0.002); and the mean CD34/L collected at MOB1 was 24.0x106 compared to 17.6x106at MOB2 (p= 0.023). The interval between MOB1 and MOB2 did not correlate with any of the MOB2 variables. Results from the analysis are summarized in Table 1. Group 2 included 32 donors. The median age was 51 years (range 21-67) and 18 were male. The median number of days between MOB1 and MOB2 was 20 (range 4-1123). 18 donors were remobilized due to mobilization failure, while 14 were remobilized due to graft failure or relapse of the recipient’s disease. The mean PB CD34/uL at MOB1 was 15 compared to 68 at MOB2 (p< 0.001); the mean CD34/kg collected at MOB1 was 2.5x106 compared to 7.1x106 at MOB2 (p< 0.001); and the mean CD34/L collected at MOB1 was 10.6x106 compared to 30.1x106at MOB2 (p< 0.001). The interval between MOB1 and MOB2 did not correlate with any of the MOB2 variables. Results from the analysis are summarized in Table 2. Conclusion: Remobilization with G-CSF or GM-CSF and G-CSF after initial successful mobilization with the same regimen results in poorer mobilization while remobilization with G-CSF after initial mobilization with a CXCR4 antagonist results in dramatically improved mobilization. The reason for this remains unclear, but in this study the interval between collections was not associated with successful remobilization. Abstract 850. Table 1 Group 1 MOB 1 MOB 2 One-way ANOVA Spearman Correlation PB CD34/ul 69 (13-417) 37 (1-115) F(1.0, 29.0) = 5.26, p= 0.029 r= 0.615, p< 0.001 CD34/kg (x106) 5.6 (0.8-13.8) 3.3 (0.3-10.6) F(1.0, 29.0) = 11.77, p= 0.002 r= 0.483, p= 0.007 CD34/L (x106) 24.0 (4.5-72.0) 17.6 (2.8-41.3) F(1.0, 29.0) = 5.74, p= 0.023 r= 0.566, p< 0.001 Abstract 850. Table 2 Group 2 MOB 1 MOB 2 One-way ANOVA Spearman Correlation PB CD34/ul 15 (2-54) 68 (14-358) F(1.0, 31.0) = 23.16, p< 0.001 r= 0.433, p= 0.013 CD34/kg (x106) 2.5 (0.2-19.7) 7.1 (1.7-42.4) F(1.0, 31.0) = 33.84, p< 0.001 r= 0.769, p< 0.001 CD34/L (x106) 10.6 (1.4-67.1) 30.1 (6.0-165.0) F(1.0, 31.0) = 34.70, p< 0.001 r= 0.774, p< 0.001 Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3360-3360
Author(s):  
Anja B Drebes ◽  
Paul Priest ◽  
Shaila Bates ◽  
Lida Moghaddam ◽  
Edward GD Tuddenham ◽  
...  

Abstract Abstract 3360 Background: Point-of-care testing (POCT) is widely used for monitoring of the international normalized ratio (INR) in patients on oral anticoagulation with a vitamin-K antagonist (VKA) and numerous clinical studies have assessed the accuracy of this method in comparison with INR results from venous blood samples analysed in the laboratory. There is however a paucity of clinical data to support the use of POCT in patients on dual anticoagulation with low molecular weight heparin (LMWH) and a VKA during initiation of anticoagulation or bridging after a surgical procedure. Aim: To test the hypothesis whether therapeutic doses of LMWH interfere with INR measurements when using a POCT system during times of dual anticoagulation with LMWH and a VKA. To further investigate whether the effect is most pronounced once LMWH has reached peak plasma levels and less evident 10 hours and more after administration of LMWH. Methods: We prospectively collected 160 consecutive venous blood samples from patients on therapeutic doses of LMWH - Tinzaparin (175 IU/kg once daily) and a VKA commonly warfarin for INR testing in our laboratory. At the same time all patients had their INR determined on capillary blood collected by finger prick using a CoaguChek XS Pro and INR test strips with the same lot number (Roche Diagnostics Ltd, UK). 60 blood samples were collected within 3–6 hours after administration of LMWH (group 1) and 100 samples were collected 10 hours or more after the last injection of LMWH (group 2). For each sample the dose and time of the last injection of LMWH was recorded along with the time of the venepuncture and the result of the capillary INR. To ensure that we had a wide variation in the plasma concentrations of LMWH we carried out anti-Xa testing on a cross-section of venous samples The dosing advice for Warfarin was based on the INR result of the venous blood sample processed in the laboratory. Results: The correlation coefficient between the POCT INR and the laboratory INR was 0.98 in group 1 and 0.97 in group 2. In the Bland Altman analysis for group 1 the mean 95% confidence interval (CI) was 0.03 (range+/− 1.96 SD: −0.26 to +0.32) and for group 2 the mean 95% CI was 0.00 (range −0.28 to +0.29). These results are comparable to results of our internal quality control between POCT INR and laboratory INR in patients on VKA alone with a mean 95% CI of −0.02 (range −0.26 to +0.29). The mean INR was 1.8 by both methods in group 1 and 1.7 by both methods in group 2 and anti-Xa levels ranged from 0 to1.19 U/mL. A variation in the result of the POCT INR and laboratory INR of 0.5 or greater is thought to affect dosing decisions for Warfarin. Such a variation was observed in 3% (2/60) in group 1 and 2% (2/100) in group 2. Conclusion: There was good accuracy of the INR obtained with the POCT system used and this was not affected by the timing of the administration of LMWH in relation to testing. Disclosures: No relevant conflicts of interest to declare.


Nukleonika ◽  
2014 ◽  
Vol 59 (4) ◽  
pp. 145-151 ◽  
Author(s):  
Ghassan Al-Massarani ◽  
Khaled Almohamad

Abstract Purpose: Damage to vascular endothelial cells is a well recognised complication of the irradiation. Our objective was to determine the gamma-irradiation effect on the rat circulating endothelial cells (CEC). Material and methods: Eight-week old rats were divided into four groups: group 1 - rats were exposed to acute whole- -body gamma irradiation with a wide range of single doses (0.5, 1, 2, 4 and 8 Gy), group 2 - rats were exposed to fractionated low doses of irradiation (0.1, 0.5 and 1 Gy) every three days for two months, group 3 as group 2, but followed by two months of rest, group 4 were control animals. CEC (CD146 positive cells) in group 1 were counted following CD146-based immuno-magnetic separation after one day and one week, as well as at the end of experiment in the other groups. Results: Quantified CEC showed that there was a dose-dependent reduction in CEC count in group 1 (one week after irradiation) and group 2. A partial re-population of CEC was observed at the end of experiment in both group 1 and group 2 compared to control group. Group 3 showed a significant increase in CEC levels as compared with group 2 without reaching the control level. Conclusion: The number of CEC (CD146 positive cells) in rats exposed to whole-body gamma irradiation was reduced in a dose-dependent manner and it partly recovered during the two-month interval after irradiation. We suggest that CEC count may be an indicator of the radiation-induced vascular damage.


Author(s):  
S A Sayganov ◽  
A M Kuzmina-Krutetskaya

Aim. To evaluate endothelial function in patients with chronic ischemic heart disease by determining the number of circulating endothelial cells in peripheral blood. Material and methods. 71 patient with typical angina class I-III and presence of obstructive coronary artery disease according to coronary angiography were assessed, coronary anatomy was assessed on the SYNTAX Score scale and the number of CEC was determined by flow cytofluorimetry. Depending on the chosen treatment strategy patients were divided into the following groups: a group of medical therapy (group 1) - 22 patients; a group of patients requiring percutaneous coronary intervention (group 2) - 25 patients; a group of patients requiring surgical revascularization by coronary artery bypass surgery (group 3) - 24 patients. The control group consisted of 20 patients without atherosclerotic lesions of the coronary arteries. Results. Study groups do not differ by sex, age, history of smoking, the presence of hypertension, MI history (р > 0.05). In the group of patients who are scheduled to perform CABG significantly more patients with diabetes mellitus (р < 0.05) (group 1 - 3 patients (13.6%), group 2 - 4 patients (16.0%), group 3 - 7 patients (29.1%), control group - 2 patients (11.8%)). Study groups reliably differ in the anatomy of coronary lesions (SYNTAX Score in group 1 - 9.4 ± 2.7, in group 2 - 19.7 ± 5.7, in group 3 - 23.5 ± 6.0), р < 0.05. The number of CECs in the study groups is significantly higher than the generally accepted norm (р < 0.05), (group 1 - 12 (10÷16), group 2 - 14 (10÷17), group 3 - 14 (11÷17), control group - 12 (10÷16)). There are no significant differences between the groups with coronary artery disease (р > 0.05). Conclusion. Study of endothelial function by flow cytometry using monoclonal fluorescently labeled antibodies to CD146 and CD45 can be considered as a criterion for noninvasive assessment of the severity of atherosclerotic lesion of the coronary bed. (For citation: Sayganov SA, Kuzmina-Krutetskaya AM. Endothelial dysfunction and circulating endothelial cells in patients with chronic ischemic heart disease. Herald of North-Western State Medical University named after I.I. Mechnikov. 2018;10(2):27-32. doi: 10.17816/mechnikov201810227-32).


2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Ricardo Christ ◽  
Aleksandro Schafer Da Silva ◽  
Mateus Eloir Grabriel ◽  
Luan Cleber Henker ◽  
Renan Augusto Cechin ◽  
...  

  Background: Nitrate and nitrite poisoning is associated with pasture intake that has high nitrate levels and leads to acute methemoglobinemia. Pasture may accumulate nitrate under certain conditions, such as excessively fertilized soil or en­vironmental conditions that enhance the N absorption (rain preceded by a period of drought). After ingestion of plants, this substrate reaches the rumen and, in physiological conditions, is reduced to nitrite and afterward to ammonia. The aim of this study was to evaluate changes in cholinesterase activities and oxidative stress caused by subclinical poisoning for nitrate and nitrite in cattle fed with Pennisetum glaucum in three different fertilization schemes. Materials, Methods & Results: In order to perform the experimental poisoning, the pasture was cultivated in three dif­ferent paddocks: with nitrogen topdressing (urea; group 1), organic fertilizer (group 2) or without fertilizer (group 3; control). Nitrate accumulation in forage was evaluated by the diphenylamine test. After food fasting of 12 h, nine bovine were randomly allocated to one of the experimental groups and fed with fresh forage (ad libitum) from respective pad­dock. In different time points from beginning of pasture intake (0, 2, 4, 6 and 9 h) heart rate and respiratory frequency were assessed, as well as mucous membrane color and behavioral changes. Blood samples from jugular vein into vials with and without anticoagulant were collected. From blood samples, serum nitrite levels, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activity were evaluated, as well as oxidative stress through the following param­eters: levels of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS), beyond the antioxidant system by enzyme activity measurement of catalase (CAT) and superoxide dismutase (SOD). The diphenylamine test was positive to group 1 and 2, so that the pasture presented 3.16 mg/kg, 2.98 mg/kg and 1.67 mg/kg of nitrate for group 1, 2 and 3, respectively. In addition, cows from group 1 demonstrated increased (P < 0.05) nitrite levels in serum, compared to other groups, and greater heart rate after 9 h (P < 0.05). The AChE and BChE activity in group 1 showed significant increase (P < 0.05) at 4 and 6 h (AChE), and 4 and 9 h (BChE) compared to group 3. Also, NOx levels were lower at 6 and 9 h (P < 0.05) and at 9 h (P < 0.05) for animals of group 1 and 2, respectively, when compared to group 3. Furthermore, in the group 1 levels of ROS and TBARS were significantly higher (P < 0.05) after 2 and 4 h, and 6 and 9 h compared to other groups, respectively. The CAT activity increased significantly (P < 0.05) with 2 and 4 h of the experiment, but on the other hand, decreased at 6 and 9 h in group 1. Nevertheless, the animals from group 2 presented only a significant reduction in this enzyme activity at 9 h. Furthermore, SOD activity was reduced in animals of groups 1 (P < 0.05) at 4, 6 and 9 h, compared to other groups. Discussion: It was concluded that the nitrate and nitrite poisoning by pasture intake cultivated and fertilized with urea leads to increased levels of serum nitrite, as well as the cholinesterase activity and causes oxidative stress in cattle. It is conjectured that the cholinesterase activity and oxidative stress may assist in understanding the pathophysiology of changes caused by poisoning.Keywords: plant toxicology, poisoning, methemoglobin, cholinergic system, oxidative stress.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Proff ◽  
B Merkely ◽  
R Papp ◽  
C Lenz ◽  
P.J Nordbeck ◽  
...  

Abstract Background The prevalence of chronotropic incompetence (CI) in heart failure (HF) population is high and negatively impacts prognosis. In HF patients with an implanted cardiac resynchronisation therapy (CRT) device and severe CI, the effect of rate adaptive pacing on patient outcomes is unclear. Closed loop stimulation (CLS) based on cardiac impedance measurement may be an optimal method of heart rate adaptation according to metabolic need in HF patients with severe CI. Purpose This is the first study evaluating the effect of CLS on the established prognostic parameters assessed by the cardio-pulmonary exercise (CPX) testing and on quality of life (QoL) of the patients. Methods A randomised, controlled, double-blind and crossover pilot study has been performed in CRT patients with severe CI defined as the inability to achieve 70% of the age-predicted maximum heart rate (APMHR). After baseline assessment, patients were randomised to either DDD-CLS pacing (group 1) or DDD pacing at 40 bpm (group 2) for a 1-month period, followed by crossover for another month. At baseline and at 1- and 2-month follow-ups, a CPX was performed and QoL was assessed using the EQ-5D-5L questionnaire. The main endpoints were the effect of CLS on ventilatory efficiency (VE) slope (evaluated by an independent CPX expert), the responder rate defined as an improvement (decrease) of the VE slope by at least 5%, percentage of maximal predicted heart rate reserve (HRR) achieved, and QoL. Results Of the 36 patients enrolled in the study, 20 fulfilled the criterion for severe CI and entered the study follow-up (mean age 68.9±7.4 years, 70% men, LVEF=41.8±9.3%, 40%/60% NYHA class II/III). Full baseline and follow-up datasets were obtained in 17 patients. The mean VE slope and HRR at baseline were 34.4±4.4 and 49.6±23.8%, respectively, in group 1 (n=7) and 34.5±12.2 and 54.2±16.1% in group 2 (n=10). After completing the 2-month CPX, the mean difference between DDD-CLS and DDD-40 modes was −2.4±8.3 (group 1) and −1.2±3.5 (group 2) for VE slope, and 17.1±15.5% (group 1) and 8.7±18.8% (group 2) for HRR. Altogether, VE slope improved by −1.8±2.95 (p=0.31) in DDD-CLS versus DDD-40, and HRR improved by 12.9±8.8% (p=0.01). The VE slope decreased by ≥5% in 47% of patients (“responders to CLS”). The mean difference in the QoL between DDD-CLS and DDD-40 was 0.16±0.25 in group 1 and −0.01±0.05 in group 2, resulting in an overall increase by 0.08±0.08 in the DDD-CLS mode (p=0.13). Conclusion First results of the evaluation of the effectiveness of CLS in CRT patients with severe CI revealed that CLS generated an overall positive effect on well-established surrogate parameters for prognosis. About one half of the patients showed CLS response in terms of improved VE slope. In addition, CLS improved quality of life. Further clinical research is needed to identify predictors that can increase the responder rate and to confirm improvement in clinical outcomes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Biotronik SE & Co. KG


2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Tesic ◽  
L Travica ◽  
V Giga ◽  
D Trifunovic ◽  
I Jovanovic ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Since mitral regurgitation (MR) is a very common finding in patients with hypertrophic cardiomyopathy (HCM), the evaluation of the mitral valve anatomy and the degree of MR is of utmost importance in this population. However, data regarding the prognostic value of different degrees of MR in HCM remains scarce. Purpose The aim of this study was to determine whether the presence of a higher degree of MR affects: 1) long term prognosis; 2) clinical and echocardiographic presentation of HCM patients. Material and Methods We included prospectively 102 patients, diagnosed with primary asymmetric HCM. The degree of MR was determined echocardiographicaly according to current recommendations of the American Association of Echocardiography. According to the MR severity, patients were divided into 2 groups: Group 1 (n = 52) with no/trace or mild MR and Group 2 with moderate or moderate to severe MR. All patients had clinical and echocardiographic examination, 24-hour Holter ECG and NT pro BNP analysis performed. The primary outcome was a composite of: 1) HCM related death or sudden death; 2) hospitalization due to acute heart failure; 3) sustained ventricular tachycardia; 4) ischemic stroke. Results Patients with higher MR degree had more frequent chest pain (p = 0.039), syncope (p = 0.041) and NYHA II functional class (p &lt; 0.001). Group 2 patients had mostly obstructive form of HCM (p &lt; 0.001) with more frequent presence of previous atrial fibrillation (AF) (p = 0.032), as well as the new onset of AF (p = 0.014) compared to patients in Group 1. Patients with higher MR degree had significantly more SAM (p &lt; 0.001) resulting in a more frequent eccentric MR jet (p &lt; 0.001), along with calcified mitral annulus (p = 0.007), enlarged left atrial volume index (p &lt; 0.001), and elevated right ventricular pressure (p = 0.001). As a result of higher MR grade, Group 2 had higher E/e" values (p &lt; 0.001), elevated LV filling pressure (lateral E/e’ &gt;10), as well as higher levels of NT pro BNP (p = 0.001). By Kaplan-Meier analysis we demonstrated that the event free survival rate during follow up of median 75 (IQR 48-103) months was significantly higher in Group 1 compared to the Group 2 (79% vs. 46%, p &lt; 0.001), Figure 1. After adjustment for relevant confounders, moderate/moderate to severe MR remained as an independent predictor of adverse outcome (hazard ratio 2.58, 95% CI: 1.08-6.13, p &lt; 0.001). Conclusion Presence of moderate, or moderate to severe MR was associated with poor long-term outcome of HCM patients. These results indicate the importance of an adequate MR assessment and detailed evaluation of the mitral valve anatomy in the prediction of complications and adequate treatment of patients with HCM. Abstract Figure.


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