Israel Medical Association Journal

background: many electrophysiologists recommend implantable cardioverter defibrillators for patients with Brugada syndrome who are cardiac arrest survivors or presumed at high risk of sudden death (patients with syncope or a familial history of sudden death or those with inducible ventricular fibrillation at electrophysiologic study).

objectives: To assess the efficacy and complications of ICD therapy in patients with Brugada syndrome.

Methods: The indications, efficacy and complications of ICD therapy in all patient with Brugada syndrome who underwent ICD implantation in 12 Israeli centers between 1994 and 2007 were analyzed.

Results: there were 59 patients (53 males, 89.8%) with a mean age of 44.1 years. At diagnosis 42 patients (71.2%) were symptomatic while 17 (28.8%) were asymptomatic. The indications for ICD implantation were: a history of cardiac arrest (n=11, 18.6%), syncope (n=31, 52.5%), inducible VF in symptomatic patients (n=14, 23.7%), and a family history of sudden death (n=3, 0.5%). The overall inducibility rates of VF were 89.2% and 93.3% among the symptomatic and a symptomatic patients, respectively (P=NS). During a follow-up of 4-160 (45+-35) months, all patients (except one who died from cancer) are alive. Five patients (8.4%), all with a history of cardiac arrest, had appropriate ICD discharge. Conversely, none of the patients without prior cardiac arrest had appropriate device therapy during 39+-30 month follow-up. Complications were encountered in 19 patients (32%). Inappropriate shocks occurred in 16 (27.1%) due to lead failure/dislodgment (n=5), T wave oversensing (n=2), device failure (n=1), sinus tachycardia (n=4), and supraventricular tachycardia (n=4). One patient suffered a pneumothorax and another a brachial plexus injury during the implant procedure. One patient suffered a late (2 months) perforation of the right ventricle by the implanted lead. Eleven patients (18.6%) required a reintervention either for infection (n=1) or lead problems (n=10). Eight patients (13.5%) required psychiatric assistance due to complications related to the ICD (mostly inappropriate shocks in 7 patients).

Conclusions: In this Israeli population with Brugada syndrome treated with ICD, appropriate device therapy was limited to cardiac arrest survivors while none of the other patients including those with syncope and/or inducible VF suffered an arrhythmic event. The overall complication rate was high.
 

Background: Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease. Erythropoietin-receptor is present on PMNLs[1].

Objectives: To evaluate the effect of 20 weeks of EPO[2]-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease.

Methods: Forty anemic chronic kidney disease patients, stage 4-5, were assigned to EPO and non-EPO treatment for 20 weeks. A group of 20 healthy controls was also studied. PMNL priming and PMNL-derived low grade inflammation were estimated, in vivo and ex vivo, before and after EPO treatment: The rate of superoxide release, white blood cells and PMNL counts, serum alkaline phosphatase and PMNL viability were measured. EPO-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate.

Results: EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo. Decreased low grade inflammation was reflected by reduced WBC[3] and PMNL counts and ALP[4] activity following treatment. EPO retarded the deterioration in GFR[5]. The percent of PMNLs expressing EPO-R[6] was higher before EPO treatment and correlated positively with the rate of superoxide release. After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated.

Conclusions: These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs, not related to the anemia correction. A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested.

Background: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve prognosis in congestive heart failure and are the treatment of choice in these patients; despite this, the rates of ACE-I[1] usage in heart failure patients remain low in clinical practice.

Objectives: To evaluate the rate of ACE-I/ARB[2] treatment in hospitalized patients with CHF[3], and analyze the reasons for non-treatment.

Methods: We prospectively evaluated 362 consecutive patients hospitalized with CHF. Patients were evaluated for ACE-I/ARB usage at discharge and were followed for 1 year.

Results: At hospital discharge 70% of the patients were prescribed ACE-I/ARB treatment. Only 69% received recommended target or sub-target dosages, proven to improve prognosis. This decreased to 63% and 59% at 6 months and 12 months of follow-up respectively, due to a shift from sub-target levels to low dosages. Justified reasons for under-treatment were apparent in only 25% not optimally treated discharged patients and this decreased to 12% and 4% at 6 and 12 months follow-up, respectively. Common reasons for non-treatment at discharge were hyperkalemia and elevation in serum creatinine, while hypotension and cough were more prominent at follow-up. Clinical parameters associated with increased treatment rates were ischemic heart disease and the absence of chronic renal failure. Patients receiving treatment had lower hospitalization and mortality rates.

Conclusions: ACE-I/ARB treatment is still underutilized in patients discharged from hospital with a diagnosis of CHF. Increasing the awareness of the importance of these drugs may increase the number of patients treated.

Background: Diseases causing increased pulmonary pressure will subsequently cause a dilation of the pulmonary arteries and right heart chambers.

Objectives: To assess the capability of computed tomography angiography and high resolution CT to diagnose and estimate the severity of pulmonary arterial hypertension as compared with standard means of right heart catheterization, echocardiography and pulmonary function tests.

Methods: The study included 38 patients with PHT[1] who underwent CT angiography and HRCT[2] as part of their routine evaluation. Diagnose included: primary PHT (n=20), Eisenmenger syndrome (n=6), scleroderma (n=3), thromboembolic disease (n=3), and others (n=6). Mean pulmonary artery pressure was 58 mmHg (range 39–92 mmHg) by catheterization and peak systolic pressure 79 mmHg (range 40–135) by echocardiography. Findings for the diameters of the main pulmonary artery and its main branches, the ascending aorta, the right atria and ventricle as well as the position of the interventricular septum were compared with 22 chest CT scans as compared to patients with no known clinical history of pulmonary hypertension, performed for other reasons (trauma, oncology follow-up) during the study period. Correlations were also calculated with recent right heart catheterization, echocardiography and pulmonary function tests of the study group.

Results: Mean main pulmonary artery diameter in the study group was 3.55 ± 0.66 cm, pulmonary artery/ascending aorta ratio 1.2 ± 0.29, right pulmonary artery 2.63 ± 0.49 cm, left pulmonary artery 2.57 ± 0.5 cm. All diameters were significantly different from the control group (P < 0.0001). Main and right pulmonary artery diameters correlated to the pressure measurement by echocardiography (P = 0.001). Bronchial collaterals were found in 11 patients (30%). The position of the interventricular septum correlated well with the echocardiography study.

Conclusions: The size of the main pulmonary artery on CT angiography has a good predictive value regarding the severity of PHT.

Background: Carotid artery stenting is used as an alternative to surgical endarterectomy.

Objectives: To determine the outcome of CAS[1] in a retrospective cohort of patients.

Methods: Between July 1999 and March 2003, 56 consecutive patients with carotid artery stenosis who were considered ineligible for surgery were treated (45 male, 11 female, mean age 69). All cases were performed prior to the introduction of distal protective devices in Israel.

Results: Intraprocedural complications included transient neurological findings in 5 patients (8%), cerebrovascular accident in 2 (3%), hemodynamic changes in 11 (18%), and 4 procedural failures. Post-procedural complications included transient ischemic attack in 3 patients and cardiovascular accident in 6 (10%). At 30 days follow-up, three patients (5%) remained with signs of CVA[2]. Two patients (3%) died during the post-procedural period and 16 (28%) during the 5 year follow-up, one due to recurrent CVA and the remainder to non-neurological causes. Five-year carotid Doppler follow-up was performed in 25 patients (45%), which revealed normal stent flow in 21 (84%), 50–60% restenosis in 3 patients (12%) and > 70% restenosis in one patient (4%).

Conclusions: This study confirms that stent procedures are beneficial for symptomatic carotid stenosis in patients not eligible for surgery.

High mobility group box 1 is a nuclear protein participating in chromatin architecture and transcriptional regulation. When released from cells, HMGB1[1] can also act as a pro-inflammatory mediator or alarmin. Upon stimulation with lipopolysaccharides or tumor necrosis factor-alpha, HMGB1 is secreted from certain cells such as monocytes/macrophages and fosters inflammatory responses. In addition, HMGB1 is passively released from necrotic cells and mediates inflammation and immune activation. In contrast, during apoptotic cell death, nuclear HMGB1 gets tightly attached to hypo-acetylated chromatin and is not released into the extracellular milieu, thereby preventing an inflammatory response. There is accumulating evidence that extracellular HMGB1 contributes to the pathogenesis of many inflammatory diseases, including autoimmune diseases. Increased concentrations of HMGB1 have been detected in the synovial fluid of patients with rheumatoid arthritis. In animal models of RA[2], HMGB1 appears to be crucially involved in the pathogenesis of arthritis, since neutralization of HMGB1 significantly ameliorates the disease. Also, in the serum and plasma of patients with systemic lupus erythematosus we detected substantial amounts of HMGB1, which may contribute to the disease process. However, investigations of blood concentrations of HMGB1 and its relevance in human diseases are hindered by the lack of reliable routine test systems.

Medical screening is not a tangible existent tool in autoimmune disorders as it is in other illnesses. Numerous attempts are made to identify individuals destined to develop an autoimmune disease, including analysis of the genetic background, which along with the immunological profile, may assist in identifying those individuals. If these efforts turn out to be successful they may lead to the possibility of proactive measures that might prevent the emergence of such disorders. This review will summarize the attempts made to pursue autoantibodies specific for the central nervous system as potential predictors of autoimmune neurological disorders.

Idiotypic analyses of anti-DNA autoantibodies were widely reported a decade ago. More than 100 studies were conducted on one of the main analyzed idiotypes, the 16/6 Id of the anti-ssDNA monoclonal antibody. In this review we summarize current knowledge on the characteristics of the 16/6 Id[1], its link to infection and its target epitopes on other molecules known so far. This includes the modulation of T and B cell responses and gene expression by the 16/6 mAb[2] in vitro and in vivo. We focus on the ability and mechanisms by which this idiotype induces experimental lupus in naïve mice, manifested by autoantibody spread, kidney and brain involvement, and leukopenia associated with enhanced sedimentation rate. We also discuss various therapeutic modalities to treat 16/6 induced lupus in mice.