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עמוד בית
Fri, 22.11.24

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December 2015
May-Tal Rofe MD, Ran Levi PhD, Einat Hertzberg-Bigelman MSc, Pavel Goryainov MSc, Rami Barashi MD, Jeremy Ben-Shoshan MD PhD, Gad Keren MD and Michal Entin-Meer PhD
 

Background: Chronic kidney disease (CKD) is a prevalent clinical condition affecting 15% of the general population. Cardiorenal syndrome (CRS) type 4 is characterized by an underlying CKD condition leading to impairment of cardiac function and increased risk for major cardiovascular events. To date, the mechanisms leading from CKD to CRS are not completely understood. In particular, it is unclear whether the pathological changes that occur in the heart in the setting of CKD involve enhanced cell death of cardiac cells.  


Objectives: To assess whether CKD may mediate loss of cardiac cells by apoptosis. 


Methods: We established rat models for CKD, acute myocardial infarction (acute MI), left ventricular dysfunction (LVD), and sham. We measured the cardiac-to-body weight as well as kidney-to-body weight ratios to validate that renal and cardiac hypertrophy occur as part of disease progression to CRS. Cardiac cells were then isolated and the percent of cell death was determined by flow cytometry following staining with annexin-FITC and propidium iodide. In addition, the levels of caspase-3-dependent apoptosis were determined by Western blot analysis using an anti-cleaved caspase-3 antibody. 


Results: CKD, as well as acute MI and LVD, resulted in significant cardiac hypertrophy. Nevertheless, unlike the increased levels of cell death observed in the acute MI group, in the CKD group, cardiac hypertrophy was not associated with induction of cell death of cardiac cells. Caspase-3 activity was even slightly reduced compared to sham-operated controls. 


Conclusions: Our data show that while CKD induces pathological changes in the heart, it does not induce cardiac cell death. 


 

 
Yuval Konstantino MD, Tali Shafat BSc, Victor Novack MD PhD, Lena Novack PhD and Guy Amit MD MPH
 

Background: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients implanted for primary and secondary prevention of sudden cardiac death. Data on the incidence of appropriate ICD therapies in primary vs. secondary prevention are limited. 


Objectives: To compare ICD therapies and mortality in primary vs. secondary prevention of sudden cardiac death. 


Methods: We conducted a retrospective analysis of 581 consecutive patients receiving an ICD for primary (66%) or secondary (34%) prevention indications. 


Results: During long-term follow-up, 29% of patients implanted for secondary prevention received appropriate ICD therapy vs. 18% implanted for primary prevention. However, the overall 7 year mortality rate was not significantly different between the two groups (26.9%, P = 0.292). Multivariate analysis showed that patients implanted for primary prevention had a significantly lower risk of appropriate ICD therapy even after adjustment for age, left ventricular ejection fraction < 0.35 and chronic renal failure (HR 1.63, 95%CI 1.10–2.41, P = 0.015).


Conclusions: Patients implanted for secondary prevention were more likely to receive appropriate ICD therapy, with a significantly shorter time period from ICD implant to the first therapy. However, all-cause mortality was comparable between primary and secondary prevention groups. 


 

 
October 2015
Zaza Iakobishvili MD PhD, Adaya Weissler MD, Kiril Buturlin MD, Gustavo Goldenberg MD, Boris Strassberg MD, Ruth Tur MD and David Hasdai MD FESC

Background: The kinetics of high sensitivity cardiac troponin T (hs-cTnT) levels after elective, biphasic, direct-current cardioversion for persistent atrial fibrillation/flutter remains unknown.

Methods: We examined hs-cTnT kinetics in 24 patients at baseline and at 2, 6 and 24 hours post-cardioversion, and again at 7 and 30 days. We also examined levels of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, brain natriuretic peptide (BNP), and high sensitivity C-reactive protein (hs-CRP).

Results: Median (25th, 75th interquartiles) baseline hs-cTnT concentration was 19.8 (10.4, 35.2) ng/L with 14 patients presenting with levels above the 99th percentile (13 ng/L). Hs-cTnT levels did not change significantly over time although they tended to decrease by 30 days, 18.8 ng/L (12.5, 23.3). There was no significant rise in other markers of myocardial injury. Similarly, BNP and hs-CRP levels were elevated at baseline and tended to decrease over time.

Conclusions: Patients with persistent atrial fibrillation/flutter have elevated hs-cTnT levels, as part of a general rise in biomarkers such as BNP and hs-CRP, without a further rise after cardioversion. After cardioversion, there is a gradual non-significant decrease in biomarker levels over time, and thus a rise in hs-cTnT levels should not be attributed to cardioversion. 

 

Haim Shmilovich MD, Svetlana Trestman MD, Stella Bak MD, Galit Aviram MD, Shmuel Banai MD, Arie Steinvil MD and Gad Keren MD
September 2015
Ibrahim Marai MD, Monther Boulos MD and Asaad Khoury MD

Background: Left cardiac sympathetic denervation (LCSD) was reported to be effective in patients with intractable ryanodine receptor mutation-associated catecholaminergic polymorphic ventricular tachycardia (CPVT). 

Objectives: To report our experience with LCSD in calsequestrin (CASQ2) mutation-associated CPVT. 

Methods: LCSD was performed in three patients with CASQ2 mutation-associated CPVT with symptoms and exercise-induced ventricular arrhythmia despite high dose beta-blocker. 

Results: None of them experienced symptoms or exercise-induced ventricular arrhythmia after LCSD. However, all had recurrence of symptoms and/or exercise-induced ventricular arrhythmia after 6 months (6–18 months).

Conclusions: LCSD conferred short-term suppression but less than optimal long-term suppression of exercise-induced ventricular arrhythmia among CASQ2-associated CPVT patients.

 

August 2015
Guy Topaz MD, Moti Haim MD, Jairo Kusniec MD, Shirit Kazum MD, Gustavo Goldenberg MD, Gregory Golovchiner MD, Ran Kornowski MD, Boris Strasberg MD and Alon Eisen MD

Background: Cardiac resynchronization therapy (CRT) is a non-pharmacological option for patients with heart failure and interventricular dyssynchrony. Elevated red cell distribution width (RDW) reflects higher size and heterogeneity of erythrocytes and is associated with poor outcome in patients with chronic heart failure. 

Objectives: To examine the association between RDW levels and outcomes after CRT implantation.

Methods: We conducted a cohort analysis of 156 patients (126 men, median age 69.0 years) who underwent CRT implantation in our institution during 2004–2008. RDW was measured at three time points before and after implantation. Primary outcome was defined as all-cause mortality, and secondary outcome as hospital re-admissions. We investigated the association between RDW levels and primary outcome during a median follow-up of 61 months.

Results: Ninety-five patients (60.9%) died during follow-up. Higher baseline RDW levels were associated with all-cause mortality (unadjusted HR 1.35, 95%CI 1.20–1.52, P < 0.001). On multivariate analysis adjusted for clinical, electrocardiographic and laboratory variables, baseline RDW levels were associated with mortality (HR 1.33, 95%CI 1.16–1.53). RDW levels 6 months and 12 months post-implantation were also associated with mortality (HR 1.22, 95%CI 1.08–1.38, P = 0.001; and HR 1.15, 95%CI 1.01–1.32, P = 0.02, respectively). Patients who were re-admitted to hospital during follow-up (n=78) had higher baseline RDW levels as compared to those who were not (14.9%, IQR 14.0, 16.0% vs. 14.3%, IQR 13.7, 15.0%, respectively, P = 0.03). 

Conclusion: An elevated RDW level before and after CRT implantation is independently associated with all-cause mortality. 

 

July 2015
Marina Leitman MD, Laurian Copel MD, Simcha Rosenblatt MD, Josef Gurevich MD and Zvi Vered MD FACC FESC
March 2014
Orly Goitein, Yishay Salem, Jeffrey Jacobson, David Goitein, David Mishali, Ashraf Hamdan, Rafael Kuperstein, Elio Di Segni and Eli Konen
 Background: Patients with complex congenital heart disease (CHD) have a high incidence of extracardiac vascular and non-vascular malformations. Those additional abnormalities may have an impact on the precise planning of surgical or non-surgical treatment.

Objectives: To assess the role of electrocardiography-gated CT-angiography (ECG-CTA) in the routine evaluation of CHD in neonates and infants particularly for the assessment of extracardiac findings.

Methods: The study cohort comprised 40 consecutive patients who underwent trans-thoracic echocardiography (TTE) and ECG-CTA. TTE and ECG-gated CTA findings regarding extracardiac vascular structures, coronary arteries and airways were compared with surgical or cardiac catheterization findings. Scans were evaluated for image quality using a subjective visual scale (from 1 to 4). Effective radiation dose was calculated for each scan.

Results: Median age was 28 ± 88 days and mean weight 3.7 ± 1.5 kg. Diagnostic quality was good or excellent (visual image score 3–4) in 39 of 40 scans (97.5%). ECG-CTA provided important additional information regarding extracardiac vascular structures and airway anatomy, complementing TTE in 75.6% of scans. Overall sensitivity of ECG-gated CTA for detecting extracardiac findings as compared with operative and cardiac catheterization findings was 97.6%. The calculated mean effective radiation dose was 1.4 ± 0.07 mSv (range 1.014–2.3 mSv).

Conclusions: ECG-CTA is an accurate modality for demonstrating extracardiac structures in complex CHD. It provides important complementary information to TTE regarding extracardiac vascular structures and coronary artery anatomy. This modality may obviate the need for invasive cardiac catheterization, thus exposing the patient to a much lower radiation dose. 

Aleksandra Djokovic, Ljudmila Stojanovich, Milica Kontic, Natasa Stanisavljevic, Slavica Radovanovic and Dragomir Marisavljevic
Background: Antiphospholipid syndrome (APS, also known as Hughes syndrome) may manifest itself as a primary or secondary disease, most commonly with systemic lupus erythemathosus (SLE) and various cardiac manifestations. 

Objectives: To report the first results from the Serbian National Cohort study, which was started in January 2000.

Methods: Our study included 374 patients: 260 primary APS patients and 114 SLE patients with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of anticardiolipin antibodies (aCL) (immunoglobulin G and M), ß2-glycoprotein 1, and lupus anticoagulant. Echocardiography was performed in all patients, and data on myocardial infarction, unstable angina, chronic cardiomyopathy and acute heart failure were collected.

Results: There were 30.7% secondary APS patients and 9.2% primary APS patients with pseudo-infective endocarditis (P = 0.0001). Cardiac manifestations were observed in 28.7% of patients who had more than one type of antibody (category I), in 24.1% with category IIa, in 23.1% with category IIb, and in 27.8% with category IIc (P = 0.78). Age was confirmed as a significant factor for cardiac manifestations in APS patients (52.3 and 43.3 years, respectively, P = 0.001). aCL IgG and IgM positivity was related to valvular changes in all APS patients and high levels of those antibodies increased the risk of these manifestations.

Conclusions: Patients with secondary APS had a higher prevalence of valvular lesions, and some aPL types and high levels of aPL were risk factors for specific cardiac manifestations in APS patients.

November 2013
O. Havakuk, M. Entin-Meer, J. Ben-Shoshan, P. Goryainov, S. Maysel-Auslender, E.l Joffe and G. Keren
 Background: Vitamin D has been shown to induce beneficial effects on cardiovascular and renal morbidity by regulating inflammation and tissue fibrosis.

Objectives: To evaluate the effect of vitamin D analogues on cardiac function and fibrosis in an animal model of cardiorenal syndrome.

Methods: Unilateral nephrectomy was performed and myocardial infarction induced in rats. Rats were treated with vitamin D receptor activator (VDRA, paricalcitol, 40 ng/250 g x 3/week) versus a vehicle. A third group of animals, which served as the control, underwent sham surgery and received no treatment. After 4 weeks of treatment, cardiac function and fibrosis were assessed by trans-thoracic echo and histology, respectively. As a parameter of systemic inflammation, previously shown to be altered in acute coronary syndrome, T regulatory (Treg) cell levels were measured by flow cytometry. Renal dysfunction was documented by standard laboratory tests.

Results: After 4 weeks of treatment, no significant improvement in cardiac function parameters was noted following VDRA administration. VDRA treatment did not significantly alter Treg cell systemic levels. Consistently, despite a trend toward less extent of myocardial fibrosis, we found no clear beneficial effects of VDRA on myocardial tissue inflammation and remodeling.

Conclusions: Vitamin D treatment showed no beneficial effects on cardiac function parameters and fibrosis in an animal model of cardiorenal syndrome. 

May 2013
E. Nahum, U. Pollak, O. Dagan, G. Amir, G. Frenkel and E. Birk
 Background: B-type natriuretic peptide (BNP) has been shown to have prognostic value for morbidity and mortality after cardiac surgery. Less is known about its prognostic value in infants.

Objectives: To investigate the predictive value of BNP levels regarding the severity of the postoperative course in infants undergoing surgical repair of congenital heart disease.

Methods: We conducted a prospective comparative study. Plasma BNP levels in infants aged 1–12 months with congenital heart disease undergoing complete repair were measured preoperatively and 8, 24 and 48 hours postoperatively. Demographic and clinical data included postoperative inotropic support and lactate level, duration of mechanical ventilation, intensive care unit (ICU) and hospitalization stay.

Results: Cardiac surgery was performed in 19 infants aged 1-12 months. Preoperative BNP level above 170 pg/ml had a positive predictive value of 100% for inotropic score ≥ 7.5 at 24 hours (specificity 100%, sensitivity 57%) and 48 hours (specificity 100%, sensitivity 100%), and was associated with longer ICU stay (P = 0.05) and a trend for longer mechanical ventilation (P = 0.12). Similar findings were found for 8 hours postoperative BNP above 1720 pg/ml. BNP level did not correlate with measured fractional shortening.

Conclusions: In infants undergoing heart surgery, preoperative and 8 hour BNP levels were predictive of inotropic support and longer ICU stay. These findings may have implications for preplanning ICU loads in clinical practice. Further studies with larger samples are needed.

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