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1.
Nat Med ; 25(3): 487-495, 2019 03.
Article En | MEDLINE | ID: mdl-30842675

Immune responses generally decline with age. However, the dynamics of this process at the individual level have not been characterized, hindering quantification of an individual's immune age. Here, we use multiple 'omics' technologies to capture population- and individual-level changes in the human immune system of 135 healthy adult individuals of different ages sampled longitudinally over a nine-year period. We observed high inter-individual variability in the rates of change of cellular frequencies that was dictated by their baseline values, allowing identification of steady-state levels toward which a cell subset converged and the ordered convergence of multiple cell subsets toward an older adult homeostasis. These data form a high-dimensional trajectory of immune aging (IMM-AGE) that describes a person's immune status better than chronological age. We show that the IMM-AGE score predicted all-cause mortality beyond well-established risk factors in the Framingham Heart Study, establishing its potential use in clinics for identification of patients at risk.


Cytokines/immunology , Healthy Volunteers , Immunosenescence/immunology , Lymphocytes/immunology , Mortality , Adult , Aged , Aged, 80 and over , Aging/immunology , Female , Humans , Individuality , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Phenotype , Proportional Hazards Models , Young Adult
2.
JACC Cardiovasc Interv ; 11(19): 1995-2003, 2018 10 08.
Article En | MEDLINE | ID: mdl-30286857

OBJECTIVES: The WISE LE (WIRION™ EPS in Lower Extremities Arteries) study was designed to assess the clinical performance of the WIRION Embolic Protection System (EPS) in subjects undergoing lower extremity atherectomy for the treatment of peripheral artery disease. BACKGROUND: Embolization is ubiquitous during endovascular procedures for lower extremity peripheral artery disease. METHODS: The WISE LE was a multicenter study, performed in the United States and Germany. The primary endpoint was freedom from major adverse events (MAEs) occurring within 30 days post-procedure and was compared with an objective performance goal derived from historical atherectomy trials. MAE was defined as a serious adverse event that resulted in death, acute myocardial infarction, thrombosis, pseudoaneurysm, dissection (grade C or greater), or clinical perforation at the filter location, clinically relevant distal embolism, unplanned amputation, or clinically driven target vessel revascularization. The study also included a histopathological analysis of debris captured by the filter during the procedures. RESULTS: The study protocol specified enrollment of 153 patients with the primary endpoint successfully met if 18 (12.0%) or fewer MAEs occurred. A pre-specified interim analysis performed after 103 patients revealed only 2 MAEs, and the study was stopped because it had met its pre-determined metric for success. Lesion deemed not accessible by the WIRION EPS occurred in 7 patients. Debris of <1-mm, 1- to 2-mm, and >2-mm diameter were found in 98%, 22%, and 9% of patients, respectively. CONCLUSIONS: The WIRION EPS is safe and noninferior to the pre-specified performance goal in capturing debris in the vast majority of patients and with the use of a broad range of atherectomy systems.


Atherectomy/instrumentation , Embolic Protection Devices , Embolism/prevention & control , Lower Extremity/blood supply , Peripheral Arterial Disease/therapy , Aged , Atherectomy/adverse effects , Embolism/etiology , Female , Germany , Humans , Male , Middle Aged , Peripheral Arterial Disease/complications , Prospective Studies , Prosthesis Design , Risk Factors , Time Factors , Treatment Outcome , United States
3.
Circ Cardiovasc Interv ; 10(3)2017 Mar.
Article En | MEDLINE | ID: mdl-28283511

BACKGROUND: Embolic protection during carotid artery stenting reduces the rate of thromboembolic events. The Wirion Embolic Protection System is used to deploy an independent distal filter using any 0.014″ guidewire. WISE study (Wirion Study Europe) evaluated the safety and performance of Wirion Embolic Protection System in patients undergoing carotid artery stenting. METHODS AND RESULTS: A prospective, multicenter, nonrandomized, open-label, single-arm study of carotid artery stenting in high surgical risk patients was performed. The primary end point, a composite of death, stroke, and myocardial infarction at 30 days, was compared with performance goal derived from historical controls. Secondary end points were components of the primary end point and the device, angiographic, procedural, and clinical success rates. Preplanned interim analysis was performed on the first 120 patients. At interim analysis, the primary end point was significantly lower for the Wirion Embolic Protection System group, compared with historical data (3.3% versus 6.3%, respectively; P value =0.0008). Analysis of primary end point components in the WISE group, compared with the historical control group, shows numerically lower mortality (0% versus 1.7%, respectively; P=0.21), stroke (2.5% versus 4.6%, respectively; P=0.18), and myocardial infarction (0.8% versus 1.5%, respectively; P=0.50). Device, angiographic, procedural, and clinical success was achieved in 99.2%, 99.1%, 98.3%, and 96.6% of cases, respectively. CONCLUSIONS: The data suggest that independent modular filter use in carotid artery stenting in high surgical risk patients is safe and effective. The outcomes suggest that use of an independent modular filter may be associated with a lower rate of embolic complications associated with carotid stent placement. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01783639.


Carotid Stenosis/therapy , Embolic Protection Devices , Endovascular Procedures/instrumentation , Intracranial Embolism/prevention & control , Stents , Stroke/prevention & control , Aged , Aged, 80 and over , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/mortality , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Europe , Female , Humans , Intracranial Embolism/diagnostic imaging , Intracranial Embolism/etiology , Intracranial Embolism/mortality , Male , Myocardial Infarction/etiology , Prospective Studies , Prosthesis Design , Risk Factors , Stroke/diagnostic imaging , Stroke/etiology , Stroke/mortality , Time Factors , Treatment Outcome
4.
Eur Heart J Acute Cardiovasc Care ; 6(7): 632-639, 2017 Oct.
Article En | MEDLINE | ID: mdl-27069068

BACKGROUND: Patients with acute ST-elevation myocardial infarction (STEMI) and increased platelet count treated by fibrinolysis have worse outcomes. AIM: The aim of this study was to test the hypothesis that platelet blood count at admission in patients with acute STEMI treated by primary percutaneous coronary intervention affects coronary flow, myocardial perfusion and recovery of left ventricular systolic function. METHODS: A total of 174 patients presenting with acute anterior STEMI and treated with primary percutaneous coronary intervention were included and divided into subgroups of admission platelet blood count of <200 K, 200-300 K, 300-400 K and >400 K. Evaluation of coronary artery flow and myocardial blush grade was performed according to the TIMI criteria. Electrocardiographic ST elevation resolution post-primary percutaneous coronary intervention was evaluated. Doppler echocardiographic evaluation of left anterior descending coronary artery velocities early and late after primary percutaneous coronary intervention and assessment of left ventricular ejection fraction and wall motion score index (WMSI) of left ventricular and left anterior descending coronary artery territory were performed. RESULTS: Post-primary percutaneous coronary intervention TIMI, myocardial blush grade and ST elevation resolution were similar in all groups. Patients with platelet counts <200 K had higher peak diastolic left anterior descending coronary artery velocity both early and late after primary percutaneous coronary intervention, and higher prevalence of left anterior descending coronary artery velocity deceleration time exceeding 600 ms, (45.5% vs. 40%, P<0.05). Patients with platelet counts >400 K presented with worse left ventricular ejection fraction, left ventricular WMSI and left anterior descending coronary artery WMSI, and before discharge this subgroup had worse left ventricular WMSI and left anterior descending coronary artery WMSI, P<0.01. CONCLUSIONS: Patients with anterior STEMI treated by primary percutaneous coronary intervention with lower admission platelet count had higher left anterior descending coronary artery diastolic velocities, better myocardial perfusion with more patients having left anterior descending coronary artery-descending coronary artery velocity deceleration time >600 ms. Patients with higher platelet counts had lower left ventricular systolic function both at admission and before discharge.


Coronary Circulation/physiology , Coronary Vessels/diagnostic imaging , Heart Ventricles/physiopathology , Percutaneous Coronary Intervention , Recovery of Function/physiology , ST Elevation Myocardial Infarction/blood , Ventricular Function, Left/physiology , Coronary Vessels/physiopathology , Echocardiography, Doppler , Electrocardiography , Female , Heart Ventricles/diagnostic imaging , Humans , Male , Middle Aged , Platelet Count , Postoperative Period , ST Elevation Myocardial Infarction/physiopathology , ST Elevation Myocardial Infarction/surgery , Systole
5.
Echocardiography ; 33(10): 1465-1471, 2016 Oct.
Article En | MEDLINE | ID: mdl-27543440

BACKGROUND: Myocardial stunning is responsible for partially reversible left ventricular (LV) systolic dysfunction after successful primary percutaneous coronary intervention (PPCI) in patients with acute ST-elevation myocardial infarction (STEMI). AIM: To test the hypothesis that early coronary blood flow (CBF) to LV systolic function ratios, as an equivalent to LV stunning index (SI), predict recovery of LV systolic function after PPCI in patients with acute STEMI. METHODS: Twenty-four patients with acute anterior STEMI who had successful PPCI were evaluated and compared to 96 control subjects. Transthoracic echocardiography with measurement of LV ejection fraction (EF), LV, and left anterior descending (LAD) coronary artery area wall-motion score index (WMSI) as well as Doppler sampling of LAD blood velocities, early after PPCI and 5 days later, were performed. SI was evaluated as the early ratio of CBF parameters in the LAD to LV systolic function parameters. RESULTS: Early SI-LVEF well predicted late LVEF (r=.51, P<.01) and the change in LVEF (r=.48, P<.017). Early SI-LVMSI predicted well late LVEF (r=.56, P<.006) and the change in LVEF (r=.46, P<.028). Early SI-LADWMSI predicted late LVEF (r=.44, P<.028). Other SI indices measured as other LAD-CBF to LV systolic function parameters were not predictive of late LV systolic function. CONCLUSIONS: LV stunning indices measured as early LAD flow to LVEF, LVWMSI, and LADWMSI ratios well predicted late LVEF and the change in LVEF. Thus, greater early coronary artery flow to LV systolic function parameter ratios predict a better improvement in late LV systolic function after PPCI.


Echocardiography, Doppler/methods , Myocardial Stunning/diagnostic imaging , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/surgery , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/prevention & control , Female , Humans , Image Interpretation, Computer-Assisted/methods , Male , Middle Aged , Myocardial Stunning/etiology , Percutaneous Coronary Intervention , Prognosis , Recovery of Function , Reproducibility of Results , ST Elevation Myocardial Infarction/complications , Sensitivity and Specificity , Stroke Volume , Treatment Outcome , Ventricular Dysfunction, Left/etiology , Ventricular Remodeling
6.
J Interv Cardiol ; 28(2): 141-6, 2015 Apr.
Article En | MEDLINE | ID: mdl-25884897

OBJECTIVES: Our objective was to assess whether bypassing the emergency room (ER) is associated with meaningful reduction in Major Adverse Cardiac and Cerebrovascular Event (MACCE) or mortality in a large cohort of ST Elevation Myocardial Infarction (STEMI) patients. BACKGROUND: Prior studies suggest that bypassing the emergency room reduces door-to-balloon time (DBT). However, it is not clear whether this translates into reduced mortality. METHODS: We analyzed data of 1,552 consecutive patients with STEMI treated by primary percutaneous coronary intervention (PCI) and enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS) registry. Thirty percent of patients (n = 459) arrived directly to the Intensive Cardiac Care Unit or catheterization laboratory and 70% (n = 1093) were assessed first in the ER. Our primary end points were DBT, 30-day MACCE, and 30-day and 1-year mortality. Our secondary end points were pre-discharge ejection fraction less than 40%, in-hospital pulmonary edema, in-hospital cardiogenic shock, ST resolution, and duration of hospitalization. RESULTS: Bypassing the ER was associated with signficantly shorter DBT (59 vs. 97 minutes, P = 0.001). There was no difference in 30-day MACCE and 30-day or 1-year mortality between the 2 study groups. The findings were consistent in multiple subgroups, including women, anterior STEMI, off hours PCI, and patients with pain-to-door (PDT) time of less than 120 minutes. CONCLUSION: Bypassing the ER is associated with significant shortening of DBT. This reduction, however, is not associated with any change in 30-day MACCE and 30-day or 1-year mortality.


Angioplasty, Balloon, Coronary , Myocardial Infarction/therapy , Time-to-Treatment , Acute Coronary Syndrome , Aged , Emergency Service, Hospital , Female , Hospitalization , Humans , Male , Middle Aged , Registries , Time Factors
7.
Isr Med Assoc J ; 17(1): 24-6, 2015 Jan.
Article En | MEDLINE | ID: mdl-25739172

BACKGROUND: The prevalence of heart failure (HF) is increasing rapidly with high readmission rates, mainly due to fluid retention. Ultrafiltration (UF) is a mechanical method for removing fluids. Since UF was introduced only recently in Israel, the skill and experience required for outpatient congested HF patients is scarce. OBJECTIVEs: To evaluate the feasibility and safety of UF therapy in congested HF patients in outpatient clinics under a strict protocol of monitoring and therapy that we developed. METHODS: Between April and September 2013 we applied UF in our outpatient clinic to seven chronically congested HF patients with NYHA III-IV who did not respond adequately to diuretics. We administered a total of 38 courses. RESULTS: On average, 1982 ml fluid per course was removed without significant adverse events and with patients' subjective feeling of improvement. Only two courses were interrupted prematurely due to mechanical problems but were completed without harm to the patients. CONCLUSIONS: Under appropriate professional medical supervision, UF therapy in an outpatient setting is a safe and effective procedure and serves as an additional tool for managing congested HF patients who do not respond adequately to diuretics.


Ambulatory Care/methods , Diuretics/administration & dosage , Heart Failure/therapy , Ultrafiltration/methods , Aged , Feasibility Studies , Female , Humans , Israel , Male , Middle Aged , Treatment Outcome , Ultrafiltration/adverse effects
8.
Heart Int ; 10(1): e6-e11, 2015.
Article En | MEDLINE | ID: mdl-27672435

BACKGROUND: Normal left anterior descending (LAD) coronary artery as determined by coronary angiography is considered not only to reflect normal angiography but also to correlate with normal anatomy and function. However, subjects who undergo coronary angiography may differ from those who do not need to have invasive evaluation even if their functional noninvasive studies like dobutamine stress echocardiography (DSE) were normal. AIM: LAD velocities in subjects with normal angiography and those with normal DSE are equal. METHODS: A total of 244 subjects were evaluated, 78 had normal LAD by angiography and 166 had normal LAD by DSE. All had Doppler sampling of LAD velocities by transthoracic echocardiography. RESULTS: Velocity was higher in the angiographic subgroup in diastole 41 ± 23 vs 33 ± 14 cm/s, p = 0.0078; systole 18 ± 14 vs 13 ± 7 cm/s, p = 0.012; diastolic integral 12.6 ± 5 vs 9.8 ± 3.8 cm, p = 3.15 × 10(-5); systolic velocity integral 4 ± 2.9 vs 2.8 ± 1.9, p = 0.0014. While heart rate was similar in both groups, the product of diastolic velocity integral and heart rate of the LAD in the angiographic group was higher: 902 ± 450 vs 656 ± 394, p = 0.00599. Diastolic velocity deceleration time was similar in both groups. Coronary flow reserve defined as diastolic velocity ratio before and immediately after DSE correlated negatively with baseline velocity, r = -0.4. CONCLUSIONS: Mode of defining normality of coronary artery affects velocity behavior of the vessel, reflecting functional differences possibly related to microvasculature and vasodilatation.

9.
Echocardiography ; 31(5): 644-653, 2014 May.
Article En | MEDLINE | ID: mdl-25232574

BACKGROUND: Function of the microcirculation after primary percutaneous coronary intervention (PCI) is dynamic and contributes to unpredictability of recovery of left ventricular (LV) systolic function. AIM: This study was conducted to evaluate sequential Doppler velocity parameters of the left anterior descending coronary artery (LAD) in predicting recovery of global and regional LV systolic function. METHODS: Thirty-five consecutive patients, 24 males, age 59 ± 12 years, with acute anterior ST-elevation myocardial infarction (STEMI) who had primary PCI were studied. Thrombolysis in myocardial infarction (TIMI) and myocardial blush grades were evaluated. Transthoracic echocardiographic (TTE) studies, evaluation of left ventricular ejection fraction (LVEF), LAD territory wall-motion score index (WMSI), and sampling of LAD Doppler velocities up to 6 hours post-PCI, 48 hours postprocedure, and predischarge were performed. RESULTS: Thrombolysis in myocardial infarction grade before PCI averaged 0.86 ± 1.19 and post-PCI 2.89 ± 0.32, P < 0.05. Myocardial blush grade before PCI was 0.41 ± 0.98 and after PCI 2.22 ± 0.93, P < 0.05. Diastolic velocity deceleration time (DDT) in the LAD early after PCI was less than 600 ms in 16 subjects. Immediately after PCI, in subjects with DDT > 600 ms, LVEF was 38.5 ± 6% and predischarge 49.2 ± 8.7%, P = 9.77 × 10−5 and LAD-WMSI decreased from 2 ± 0.38 to 1.4 ± 0.48, P = 0.000163. In subjects with DDT < 600 ms LAD-WMSI did not change significantly. Early and minimal LAD-DDT correlated with improvement in LV systolic function, r = 0.6, whereas post-PCI blush grade had lower correlation with LVEF, r = 0.39. CONCLUSIONS: Global and regional LV systolic function after PCI in acute anterior MI can be predicted by LAD-DDT better than by post-PCI myocardial blush.


Coronary Circulation/physiology , Coronary Vessels/diagnostic imaging , Echocardiography, Doppler, Color/methods , Myocardial Infarction/physiopathology , Recovery of Function , Ventricular Function, Left/physiology , Coronary Angiography , Coronary Vessels/physiopathology , Electrocardiography , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Predictive Value of Tests , Systole
11.
Eur Heart J Acute Cardiovasc Care ; 3(3): 223-8, 2014 Sep.
Article En | MEDLINE | ID: mdl-24493865

UNLABELLED: The treatment of choice in acute ST-elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PPCI). Although, thrombolysis in myocardial infarction (TIMI) and myocardial blush grade (MBG) measures provide semi-quantitative flow evaluation after PPCI, serial and quantitative volumetric flow evaluation is still lacking. AIM: Serial assessment of left anterior descending (LAD) coronary artery flow in patients with anterior myocardial infarction (MI), immediately after PPCI, 48 h later and pre-discharge and compare findings in patients with optimal and suboptimal PPCI result and their relation to left ventricular ejection fraction (LVEF). METHODS: Velocities in the LAD were recorded within 6 h after PPCI and one week later in 36 patients presenting with acute anterior STEMI. Sixteen patients had TIMI and MBG less than 3 after PPCI were considered to have suboptimal result. Sampling of LAD coronary artery velocity was obtained from trans-thoracic Doppler. Flow in the LAD coronary artery was estimated using heart rates, Doppler time velocity integrals and LAD color Doppler diameters. RESULTS: Diastolic LAD coronary artery flow immediately after PPCI in subjects with suboptimal PPCI, 29 ± 21 ml/min was lower than in those with optimal result, 39.8 ± 21 ml/min, p<0.05. Diastolic flow in the LAD coronary artery increased to 50.3 ± 28.5 ml/min two days after PPCI in patients with suboptimal PPCI, p=0.04, and to 49.6 ± 13.8 ml/min in those optimal result, p=0.04. LVEF increased by 9% in patients with optimal PPCI, p=0.004, and did not change in the other group. CONCLUSIONS: (a) After PPCI, flow in the LAD coronary artery was dynamic; (b) in the presence of suboptimal PPCI, early LAD coronary artery flow was reduced; (c) pre-discharge, LAD coronary artery flow increased; and (d) LVEF increased only in optimal PPCI group associated with higher early LAD coronary artery flow.


Anterior Wall Myocardial Infarction/physiopathology , Coronary Circulation/physiology , Coronary Vessels/physiology , Ventricular Dysfunction, Left/physiopathology , Anterior Wall Myocardial Infarction/pathology , Anterior Wall Myocardial Infarction/therapy , Blood Flow Velocity/physiology , Coronary Vessels/pathology , Diastole/physiology , Electrocardiography , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention , Postoperative Period , Recovery of Function/physiology , Stroke Volume/physiology , Systole/physiology , Treatment Outcome
12.
Am J Cardiol ; 112(9): 1516-9, 2013 Nov 01.
Article En | MEDLINE | ID: mdl-23993117

Evidence-based medicine demands considerable time and decision-making skills to navigate through the proliferating data. A hierarchical "pyramid of evidence" has been formulated to help categorize data quality. The hierarchical data are processed into recommendations in Practice Guideline statements. Recently, both American College of Cardiology/American Heart Association/Society for Cardiac Angiography and Interventions and European Society of Cardiology guidelines for percutaneous coronary intervention embraced a new "heart team approach" as the preferred method to optimize revascularization decision making in cases of complex coronary anatomy. This extrapolation of a research method to the broad clinical practice has potential limitations. We suggest that both the need for a new method to optimize patient triage for the various revascularization strategies and the method to optimize decision making should be discussed. Published data suggest only minor deviations from guideline-based indications. Furthermore, traditional clinical judgment may result in a better patient outcome than arbitrary treatment assignment by rigid set of criteria. In conclusion, the need for a new decision-making process in the choice of revascularization strategy should be further explored and supported by scientific evidence.


American Heart Association , Cardiology/methods , Coronary Artery Disease/surgery , Evidence-Based Medicine/methods , Myocardial Revascularization/standards , Patient Care Team , Decision Making , Humans , Patient Selection , United States
13.
EuroIntervention ; 8(9): 1026-32, 2013 Jan 22.
Article En | MEDLINE | ID: mdl-23339808

AIMS: Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy in the treatment of carotid artery disease. The use of an embolic protection device (EPD) can reduce the frequency of embolic events during CAS. Difficult vascular anatomy may complicate current generation EPD placement. This problem is addressed by a new EPD, the GARDEX System. The aim of this study was to assess the safety and performance of the GARDEX EPD during CAS. METHODS AND RESULTS: Thirty-eight patients underwent CAS with the GARDEX EPD in two medical centres. All patients were prospectively followed up for 30 days. Device performance and procedural details were collected and analysed prospectively. Vessel anatomy and lesion morphology were evaluated and stratified into a scoring system for anatomic difficulty. More than a third of the patients were considered to have difficult vascular anatomy for CAS. All enrolled patients were successfully treated. There was one (2.6%) minor periprocedural stroke and there were two (5.3%) periprocedural TIAs which resolved within 24 hours. No additional complications were noted during the 30-day follow-up period. CONCLUSIONS: In this first experience, CAS under cerebral protection with the GARDEX EPD was safe and feasible. Our data suggest that the use of the GARDEX EPD is simple and shows high success rates even in challenging anatomies. The role of this new device in CAS needs to be further confirmed in a larger patient population.


Angioplasty/instrumentation , Carotid Stenosis/therapy , Embolic Protection Devices , Embolism/prevention & control , Stents , Adult , Aged , Aged, 80 and over , Angiography , Angioplasty/methods , Cardiac Catheters , Embolism/complications , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Risk Factors , Stroke/epidemiology , Stroke/prevention & control , Treatment Outcome
14.
Am Heart J ; 165(2): 234-40.e1, 2013 Feb.
Article En | MEDLINE | ID: mdl-23351827

BACKGROUND: Activation of systemic innate immunity is critical in the chain of events leading to restenosis. LABR-312 is a novel compound that transiently modulates circulating monocytes, reducing accumulation of these cells at vascular injury sites and around stent struts. The purpose of the study was to examine the safety and efficacy of a single intravenous bolus of LABR-312 in reducing restenosis in patients treated for coronary narrowing. Patient response was examined in light of differential inflammatory states as evidenced by baseline circulating monocyte levels, diabetes mellitus, and acute coronary syndrome. METHODS: BLAST is a Phase II prospective, randomized, multicenter, double-blind, placebo-controlled trial that assessed the safety and efficacy of LABR-312. Patients were randomized to receive LABR-312 at 2 dose levels or placebo as an intravenous infusion during percutaneous coronary intervention and bare metal stent implantation. The primary end point was mean angiographic in-stent late loss at 6 months. RESULTS: Patients (N = 225) were enrolled at 12 centers. There were no safety concerns associated with the study drug. For the overall cohort, there were no differences between the groups in the primary efficacy end point (in-stent late loss of 0.86 ± 0.60 mm, 0.83 ± 0.57 mm, and 0.81 ± 0.68 mm for the placebo, low-dose, and high-dose group, respectively; P = not significant for all comparisons). In the prespecified subgroups of patients with a baseline proinflammatory state, patients with diabetes mellitus, and patients with high baseline monocyte count, there was a significant treatment effect. CONCLUSIONS: Intravenous administration of LABR-312 to patients undergoing percutaneous coronary intervention is safe and effectively modulates monocyte behavior. The average late loss did not differ between the treatment and placebo groups. However, in the inflammatory patient group with baseline monocyte count higher than the median value, there was a significant reduction in late loss with LABR-312.


Alendronate/administration & dosage , Coronary Restenosis/therapy , Stents , Administration, Intravenous , Coronary Angiography , Coronary Restenosis/diagnostic imaging , Dose-Response Relationship, Drug , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Ischemia/surgery , Percutaneous Coronary Intervention , Prospective Studies , Treatment Outcome
15.
Cardiol Res ; 4(4-5): 139-144, 2013 Oct.
Article En | MEDLINE | ID: mdl-28352436

BACKGROUND: Right ventricular (RV) systolic performance is more difficult for evaluation compared to the left ventricle (LV). Despite differences in structure, RV myocardial fibers are in continuity with those of LV. The aim is assessment of the effects of LV wall motion abnormalities (WMA) on RV systolic function at rest and after stress. METHODS: Fifty nine subjects, 15 with LV-WMA underwent dobuatmine stress echocardiography (DSE) studies using the usual protocol. Measurement of tricuspid annular plane systolic excursion (TAPSE), velocity (TASV), mitral annular plane systolic excursion (MAPSE) and velocity (MASV), were performed before and immediately after DSE studies. RESULTS: TAPSE was lower, in those with LV-WMA than in those without, both at rest 20.5 ± 4.8 mm versus 24.9 ± 4.7 mm, P = 0.015 and after DSE studies, 21.5 ± 5.6 mm versus 27.65 ± 5.7 mm, P = 0.005. DSE studies did not change TAPSE significantly in the presence of LV-WMA. TASV at rest in those with LV-WMA was 16.5 ± 2.7 cm/sec and similar to that in those without, 17.6 ± 3 cm/sec. In both groups the velocity increased after DSE studies, 23.25 ± 7.5 cm/sec, P = 0.01 with LV-WMA, and 27.5 ± 6 cm/sec, P = 0.0005, without LV-WMA. Despite similar TASV at rest, the TAPSE/TASV ratio, indicating duration of shortening, was lower (124 ± 21 msec) in subjects with of LV-WMA, than in those without (145 ± 27 msec), P = 0.0065, implying increased after load for RV longitudinal shortening in the presence of LV-WMA. CONCLUSIONS: TAPSE is lower at rest and after DSE studies in subjects with LV-WMA than in subjects without; however, DSE studies increase TPASE only in the absence of LV-WMA. TASV increases after DSE studies and is similar at rest in both groups with or without LV-WMA. It seems that LV-WMA increases after load to RV longitudinal motion.

17.
Med Sci Sports Exerc ; 44(5): 776-85, 2012 May.
Article En | MEDLINE | ID: mdl-22005747

PURPOSE: The study's purpose was to analyze the effects of exercise training on exercise tolerance and left ventricular systolic function and structure in heart failure patients with preserved, mild, and moderate to severe reduction of left ventricular ejection fraction (LVEF). METHODS: Ninety-eight patients with moderate to severe (n = 34), mild (n = 33), and preserved (n = 31) LVEF were randomly assigned to exercise training plus usual care (n = 65) or usual care alone (n = 33) in a randomization ratio of 2:1. Left ventricular function, left ventricular dimensions, and exercise tolerance were assessed before and after each intervention. RESULTS: Exercise tolerance and LVEF increased with exercise training in all patient groups, whereas they remained unchanged after usual care alone. Exercise training increased the mean ratio of early to late mitral inflow velocities (E/A ratio) and decreased deceleration time (DT) of early filling in patients with mild and preserved LVEF. In patients with moderate to severe systolic dysfunction and advanced diastolic dysfunction (DT < 160 ms), exercise training decreased E/A ratio and increased DT, both of which were unchanged after usual care alone. In the remaining patients (DT > 160 ms), exercise training also improved mitral inflow patterns. Exercise training decreased left ventricular dimensions in patients with mild and moderate to severe reduction of LVEF but not in patients with preserved LVEF. CONCLUSIONS: These results indicate that exercise training can improve the course of heart failure independent of the degree of baseline left ventricular dysfunction.


Diastole/physiology , Exercise Therapy/methods , Heart Failure/rehabilitation , Ventricular Dysfunction, Left/rehabilitation , Analysis of Variance , Blood Flow Velocity/physiology , Chi-Square Distribution , Echocardiography , Exercise Test , Exercise Tolerance/physiology , Female , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Humans , Male , Middle Aged , Stroke Volume/physiology , Systole/physiology , Treatment Outcome , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology
18.
Isr Med Assoc J ; 13(4): 216-9, 2011 Apr.
Article En | MEDLINE | ID: mdl-21598809

BACKGROUND: Rapid reperfusion of an infarct-related artery is crucial for the successful treatment of ST elevation myocardial infarction. Every effort should be made to shorten door-to-balloon time. OBJECTIVES: To investigate whether bypassing the emergency room (ER) has a positive influence on door-to-balloon time in patients presenting with ST elevation myocardial infarction (STEMI) and whether the reduction in door-to-balloon time improves patients' clinical outcome. METHODS: We analyzed data of 776 patients with STEMI from the 2004 and the 2006 Acute Coronary Syndrome Israeli Survey (ACSIS) registry. The ACSIS is a biennial survey on acute myocardial infarction performed in all 25 intensive cardiac care units in Israel during a 2-month period. Twenty-five percent of patients (193 of 776) arrived directly to the intensive cardiac care unit (ICCU) and 75% (583 of 776) were assessed first in the ER. We compared door-to-balloon time, ejection fraction, 30 days MACE (major adverse cardiac and cerebrovascular events) and 30 days mortality in the two study groups. RESULTS: There was significantly shorter door-to-balloon time in the direct ICCU group as compared with the ER group (45 vs. 79 minutes, P< 0.002). Patients in the direct ICCU group were more likely to have door-to-balloon time of less than 90 minutes in accordance with ACC/AHA guidelines (88.7% vs. 59.2%, P < 0.0001). Moreover, patients in the direct ICCU group were less likely to have left ventricular ejection fraction < 30% (5.4% vs. 12.2%, P= 0.045) and less likely to have symptoms of overt congestive heart failure. Lastly, 30 days MACE was significantly lower in the direct ICCU group (22 vs. 30%, P< 0.004). CONCLUSIONS: There is significant reduction of the door-to-balloon time in the direct ICCU admission strategy. This reduction translates into improvement in clinical outcome of patients. It is reasonable to apply the direct ICCU strategy to patients with STEMI.


Emergency Service, Hospital , Intensive Care Units , Myocardial Infarction/therapy , Outcome Assessment, Health Care , Aged , Angioplasty, Balloon, Coronary , Female , Hospitalization/trends , Humans , Israel , Male , Middle Aged
19.
Pacing Clin Electrophysiol ; 34(7): 875-83, 2011 Jul.
Article En | MEDLINE | ID: mdl-21410732

BACKGROUND: QRS width and echocardiography-derived indices are limited predictors of response to resynchronization therapy. We applied digital palpography, using vibration resonance imaging, to investigate the effects of right ventricular pacing and left ventricular ejection fraction (LVEF) on mechanical and electrical dyssynchrony. METHODS: Forty-nine subjects were examined: 24 normal controls, 18 subjects with right ventricular apical pacing (12 with reduced LVEF), and seven subjects with reduced LVEF and narrow QRS. Digital measurement of QRS width was performed. Electric dyssynchrony index (EDI) was measured as the time interval between peak R-waves of the same QRS complex of simultaneously recorded standard limb electrocardiograms, L1 and L2. A matrix of 6 × 6 vibration recording transducers was applied to chest. The interval between the onset of Q-wave and the peak of amplitude vibration for each transducer was measured, and a three-dimensional map for the whole matrix of transducers was generated. Median values (QE1) were measured. Mechanical vibration systolic dyssynchrony index (VSDI) for each subject was determined as the standard deviation of the difference between the median value and each transducer interval. RESULTS: EDI was larger in subjects with right ventricular pacing. Mechanical dyssynchrony indices were larger with pacing and reduced LVEF. EDI correlated with QRS width (r(2) = 0.7), with VSDI (r(2) = 0.42), and with QE1 (r(2) = 0.74). QRS width correlated with QE1 (r(2) = 0.75). CONCLUSIONS: Digital chest palpography can determine dyssynchrony indices that are larger in subjects with right ventricular pacing and reduced LVEF and correlate with parameters of electrical dyssynchrony.


Cardiac Resynchronization Therapy , Heart Ventricles/physiopathology , Stroke Volume , Ventricular Dysfunction, Left , Adult , Aged , Electrocardiography , Female , Humans , Male , Middle Aged
20.
Cardiol Res ; 2(1): 36-41, 2011 Feb.
Article En | MEDLINE | ID: mdl-28348658

BACKGROUND: Mitral annular systolic displacement from M-mode echocardiography and velocity from tissue Doppler imaging reflect subendocardial longitudinal systolic LV performance and may precede radial abnormalities. The aim of this study is to evaluate the utility of mitral annular systolic displacement (D) and velocity (V) during dobutamine stress echocardiography (DSE) in detecting left ventricular (LV) functional reserve and wall motion abnormality (WMA). METHODS AND RESULTS: Fifty-nine subjects, 15 with resting WMA, underwent DSE and measurement of mitral systolic (D) and (V) before and immediately after DSE. Annular septal (D) was lower in those with WMA than in those without, at rest 10.5 ± 4 cm versus 13.2 ± 2 cm, p = 0.015, and after DSE, 11.7 ± 3.8 cm versus 14 ± 2.25 cm, p = 0.036, but without significant change after stress. Annular systolic (V) at rest with WMA was 9.7 ± 1.8 cm/sec and similar to those without, 11.25 ± 2.7 cm/sec. In both groups the velocity increased after DSE, 14.5 ± 4.5 cm/sec, p = 0.025 with WMA and 17.8 ± 3.2 cm/sec, p = 1.99 x 10-10 in those without WMA. Velocities after DSE were lower in those with WMA, p = 2.25 x 10-6. CONCLUSIONS: To evaluate LV systolic performance mitral annular systolic longitudinal displacement is valuable at rest, but for assessment of LV functional reserve after stress velocities are better.

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