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עמוד בית
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March 2022
Ortal Tuvali MD, Gal Sella MD, Dan Haberman MD, Valeri Cuciuc MD, and Jacob George MD

The pathogenesis of atherosclerosis is multifactorial, mainly driven by complex inflammatory processes. Colchicine is an anti-inflammatory drug used in a variety of clinical settings. The purpose of this review is to evaluate the role of colchicine in atherosclerotic vascular disease and more specifically, its promising impact on the outcome of patients with stable and acute coronary syndrome and to review its effect in patients undergoing angioplasty. A literature review was performed using the search terms colchicine, coronary heart disease, or acute coronary syndrome, stable coronary disease. We accessed PubMed, Google scholar, and the Cochrane Library databases to search for studies. Patients with chronic coronary disease may benefit from treatment with low dose colchicine to reduce the occurrence of a cardiovascular event. Among patients with a recent myocardial infarction, colchicine treatment was associated with reduced ischemic cardiovascular events, although without a meaningful difference in mortality. Colchicine was found to be a promising agent that can be potentially integrated into the armamentarium of treatments for patients with atherosclerotic coronary disease pending careful patient selection

October 2021
Nicholay Teodorovich MD, Michael Jonas MD, Dan Haberman MD, Haitham Abu Khadija MD‏, Omar Ayyad MD, Gera Gandelman MD, Lion Poles MD, Jacob George MD, and Alex Blatt MD MSc

Background: Anti-endothelial cell antibodies (AECA) are a known biomarker of endothelial dysfunction and damage in clinical practice, especially in autoimmune disease.

Objectives: To determine the relation between natural AECA levels and prognosis related to coronary artery disease.

Methods: Candidates for coronary angiography were prospectively enrolled. AECA levels were determined by ELISA assay. Mortality was evaluated after more than 5 years follow-up.

Results: Of a total 857 patients, 445 had high AECA levels (group 1) and 412 had low levels (< 1 OD unit, group 2). Both groups did not differ in age, sex, or presence of diabetes. The median follow up was 2293 days (76 months). Patients with high AECA levels were more likely to have normal coronary arteries on angiography (21.6% vs. 16.9%, P = 0.047) and less likely to have calcified lesions (19.0% vs. 26.6%, P = 0.028) and lower prevalence of abnormal renal functions (71.1 mg/dl vs. 66.5 mg/dl, P = 0.033). Patients with higher AECA levels had lower mortality levels (20.1% vs. 27.6%, P = 0.006). A logistic regression model demonstrated independent association between lower AECA levels and the presence of coronary atherosclerosis based on angiogram.

Conclusions: After a median of more than 6 years, higher natural AECA levels were associated with less coronary artery disease and lower mortality rates in patients undergoing coronary angiography

December 2018
Sorel Goland MD, Irena Fugenfirov MD, Igor Volodarsky MD, Hadass Aronson MD, Liaz Zilberman MD, Sara Shimoni MD and Jacob George MD

Background: Early identification of patients with a likelihood of cardiac improvement has important implications for management strategies.

Objectives: To evaluate whether tissue Doppler imaging (TDI) and two-dimensional (2D) strain measures may predict left ventricular (LV) improvement in patients with recent onset dilated cardiomyopathy (ROCM).

Methods: Clinical and comprehensive echo were performed at baseline and at 6 months. Patients who achieved an increase of ≥ 10 LV ejection fraction (LVEF) units and LV reverse remodeling (LVRR) (group 1) and those who improved beyond the device threshold achieving LVEF of ≥ 0.40 (group 2) were compared to patients who did not improve to this level.

Results: Among 37 patients with ROCM (mean age 56.3 ± 12.9 years and LVEF 29.1 ± 7.0%), 48% achieved LVEF ≥ 0.40 and 37.8% demonstrated LVRR. Patients with LVEF improvement ≥ 40% presented at diagnosis with higher LVEF (P = 0.006), smaller LV end-diastolic diameter (LVEDd) (P = 0.04), higher E’ septal (P = 0.02), lower E/E’ ratio (P = 0.02), increased circumferential strain (P = 0.04), and apical rotation (P = 0.009). Apical rotation and LVEDd were found to be independent predictors of LVRR. End-systolic LV volume was a significant predictor of LVEF improvement (≥ 40%).

Conclusions: Nearly half of the patients with ROCM demonstrated cardiac function improvement beyond the device threshold by 6 months. Apical rotation was introduced in our study as 2D strain prognostic parameter and found to be an independent predictor of LVRR. LV size and volume were predictors of LV improvement.

April 2014
Sarah Kraus PhD, Inna Naumov PhD, Shiran Shapira PhD, Dina Kazanov MSc, Ilan Aroch MSc, Arnon Afek MD PhD, Oded Eisenberg PhD , Jacob George MD, Nadir Arber MD MSc MHA and Ariel Finkelstein MD
 Background: Atherosclerosis is a complex vascular inflammatory disease. In the last decade it was suggested that non-steroidal anti-inflammatory drugs (NSAID) and in particular inhibition of cyclooxygenase (COX)-2 are associated with an increase in cardiovascular morbidity and mortality. Aspirin is known to reduce the incidence and mortality from ischemic heart disease and is a mainstay in the prevention of vascular complications of atherosclerosis.

Objectives: To examine the effect of meloxicam, a selective COX-2 inhibitor, or low dose aspirin on the development of experimental atherosclerosis in apoE knockout (KO) compared to wild-type (WT) mice. We aimed to test the hypothesis that meloxicam, a potential vasculitis inducer, would exacerbate atherosclerotic lesions while aspirin, which is known to reduce the incidence of thrombosis occlusive events, would increase protection in this model.

Methods: We randomly divided 36 male apoE KO and 36 WT mice, 8 weeks old. Mice were treated for 10 weeks with 0.1 mg/ml aspirin, or 0.05 mg/ml meloxicam, dissolved in their drinking water. Control groups received regular drinking water. At sacrifice, the hearts were removed for histochemical staining and plaque size and composition were examined.

Results: Aspirin-treated animals displayed a decreased atherosclerotic lesion area compared to the untreated control mice, while meloxicam had a null effect on the extent of atherosclerosis in Apo E KO mice.

Conclusions: These results suggest that low dose aspirin reduces early atherosclerosis, while inhibition of COX-2 by meloxicam is not associated with an increase in atherosclerotic plaque size in this mouse model.

November 2010
A. Finkelstein, S. Schwartzenberg, L. Bar, Y. Levy, A. Halkin, I. Herz, S. Bazan, R. Massachi, S. Banai, G. Keren and J. George

Background: ST-elevation myocardial infarction is caused by occlusive coronary thrombosis where antecedent plaque disruption occurs. When treating STEMI[1] the main goal is to achieve prompt reperfusion of the infarction area. Several studies have demonstrated the efficacy of an aspiration device before percutaneous coronary intervention in patients with acute myocardial infarction.

Objectives: To determine the added value of thrombus aspiration prior to primary PCI[2] by comparing AMI[3] patients with totally occluded infarct-related artery treated with routine primary PCI to those treated with extraction device prior to primary PCI.

Methods: The study group comprised 122 consecutive patients with AMI and a totally occluded infarct artery (TIMI flow 0) who underwent primary PCI. The patients were divided into two groups: 68 who underwent primary PCI only (control group) and 54 who underwent primary thrombus extraction with an extraction device before PCI (extraction group). Baseline clinical and lesion characteristics were similar in both groups. Final TIMI grade flow and myocardial blush as well as 1 year mortality, target lesion revascularization, recurrent myocardial infarction, unstable angina and stroke were compared between the two groups.

Results: Primary angiographic results were better for the extraction group versus the control group: final grade 3 TIMI flow was 100% vs. 95.6% (P = 0.03) and final grade 3 myocardial blush grade 50% vs. 41.18% (although P was not significant). Long-term follow-up total MACE[4] showed a non-significant positive trend in the extraction group (12.96% vs. 24.71%, P = 0.26).

Conclusions: The use of extraction devices for intracoronary thrombectomy during primary PCI in patients with totally occluded infarct artery significantly improved epicardial reperfusion in the infarct-related vessel and showed a trend for more favorable long-term outcome.






[1] STEMI = ST-elevation myocardial infarction



[2] PCI = percutaneous coronary intervention



[3] AMI = acute myocardial infarction



[4] MACE = major adverse cardiac event


December 2008
Y. Michowitz, S. Kisil, H. Guzner-Gur, A. Rubinstein, D. Wexler, D. Sheps, G. Keren, J. George

Background: Myeloperoxidase levels were shown to reflect endothelial dysfunction, inflammation, atherosclerosis and oxidative stress.

Objectives: To examine the role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor of mortality in patients with congestive heart failure.

Methods: Baseline serum MPO[1] levels were measured in 285 consecutive CHF[2] patients and 35 healthy volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C-reactive protein concentrations were also measured. The primary outcome endpoint was overall mortality.

Results: MPO levels were significantly elevated in patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow-up of 40.9 ± 11.3 months there were 106 deaths. On a univariate Cox regression analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP[3] was of considerable value (P < 0.0001) in predicting all-cause mortality. By dividing our cohort according to NT-proBNP levels into high, intermediate and low risk groups a clear difference in mortality was shown. By further dividing the patient cohort according to MPO levels above or below the median (122.5 ng/ml), mortality prediction improved in the patients with intermediate NT-proBNP values.


Conclusions: MPO levels are elevated in CHF and correlate with disease severity. MPO has an additive predictive value on mortality in patients with intermediate NT-proBNP levels.

 


 


[1] MPO = myeloperoxidase

[2] CHF = congestive heart failure

[3] NT-proBNP = N-terminal pro-brain natriuretic peptide

June 2006
A. Glick, Y. Michowitz, G. Keren and J. George
 Background: Cardiac resynchronization therapy is a modality with proven morbidity and mortality benefit in advanced systolic heart failure. Nevertheless, not all patients respond favorably to CRT[1]. Natriuretic peptides and inflammatory markers are elevated in congestive heart failure and reflect disease severity.

Objectives: To test whether an early change in neurohormonal and inflammatory markers after implantation can predict the clinical response to CRT.

Methods: The study group included 32 patients with advanced symptomatic systolic heart failure and a prolonged QRS complex and who were assigned to undergo CRT. Baseline plasma levels of B-type natriuretic peptide and high sensitivity C-reactive protein were determined in the peripheral venous blood and coronary sinus. Post-implantation levels were determined 2 weeks post-procedure in the PVB[2]. Baseline levels and their change in 2 weeks were correlated with all-cause mortality and hospitalization for congestive heart failure.

Results: At baseline, coronary sinus levels of BNP[3] but not hsCRP[4] were significanly elevated compared to the PVB. Compared to baseline levels, BNP and hsCRP decreased significantly within 2 weeks after the implantation (BNP mean difference 229.1 ± 102.5 pg/ml, 95% confidence interval 24.2–434, P < 0.0001; hsCRP mean difference 5.2 ± 2.4 mg/dl, 95% CI[5] 0.3–10.1, P = 0.001). During a mean follow-up of 17.7 ± 8.2 months 6 patients died (18.7%) and 12 (37.5%) were hospitalized due to exacerbation of CHF[6]. Baseline New York Heart Association and CS[7] BNP levels predicted CHF-related hospitalizations. HsCRP levels or their change over 2 weeks did not predict all-cause mortality or hospitalizations.

Conclusions: BNP levels in the CS and peripheral venous blood during biventricular implantation and 2 weeks afterwards predict cilinical response and may guide patient management.


 





[1] CRT = cardiac resynchronization therapy

[2] PVB = peripheral venous blood

[3] BNP = B-type natriuretic peptide

[4] hs-CRP = high sensitivity C-reactive protein

[5] CI = confidence interval

[6] CHF = congestive heart failure

[7] CS = coronary sinus


October 1999
Jacob George, MD, Dror Harats, MD and Yehuda Shoenfeld, MD
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