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עמוד בית
Sat, 18.05.24

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March 2024
Batia Kaplan PhD, Rivka Goldis MSc, Tamar Ziv PhD, Amir Dori MD PhD, Hila Magen MD, Amos J Simon PhD, Alexander Volkov MD, Elad Maor MD PhD, Michael Arad MD

Background: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA).

Objectives: To demonstrate the utility of the Western blotting (WB)-based amyloid typing method in patients diagnosed with cardiac amyloidosis where the type of amyloid was not obvious based on the clinical context.

Methods: Congo red positive endomyocardial biopsy specimens were studied in patients where the type of amyloid was uncertain. Amyloid proteins were extracted and identified by WB. Mass spectrometry (MS) of the electrophoretically resolved protein-in-gel bands was used for confirmation of WB data.

Results: WB analysis allowed differentiation between AL, AA, and ATTR in cardiac biopsies based on specific immunoreactivity of the electrophoretically separated proteins and their characteristic molecular weight. The obtained results were confirmed by MS.

Conclusions: WB-based amyloid typing method is cheaper and more readily available than the complex and expensive gold standard techniques such as MS analysis or immunoelectron microscopy. Notably, it is more sensitive and specific than the commonly used immunohistochemical techniques and may provide an accessible diagnostic service to patients with amyloidosis in Israel.

August 2023
Andre Keren MD, Rabea Asleh MD PhD MHA, Edo Y. Birati MD, Tuvia Ben Gal MD, Michael Arad MD

Recognizing myocarditis is a diagnostic and therapeutic challenge due to the heterogeneity of its clinical presentation and the wide range of etiologies. There is a lack of uniformity among position papers and guidelines from various professional societies regarding the definition and diagnostic workout, including recommendations for performing endomyocardial biopsy (EMB) and medical management, especially the use of immunosuppressive regimens [1-3]. Moreover, there is significant variability among medical centers in Israel in the diagnostic and therapeutic approaches to acute myocarditis. The purpose of this position paper is to present ways to standardize the management of acute myocarditis in Israel [4] by providing up-to-date definitions of the clinical categories of myocarditis, diagnostic criteria, and therapeutic approaches that correspond to the realities of our healthcare system.

Andre Keren MD, Rabea Asleh MD PhD MHA, Edo Y. Birati MD, Tuvia Ben Gal MD, Michael Arad MD

In the position statement on the definition and diagnosis of acute myocarditis on page XXX of this issue of the Israel Medical Association Journal (IMAJ), we discussed contemporary criteria for definition of acute myocarditis and inflammatory cardiomyopathy [1-6]. We also addressed current diagnostic methods including indications for endomyocardial biopsy (EMB) [7-21]. In this position statement, we discuss the management approaches during hospitalization and following hospital discharge, including specific forms of myocarditis and recommendations for returning to physical activity after myocarditis [21-36].

July 2021
Jacob Weinstein MD, Amichai Shinfeld MD, Michal Simchen MD, Tal Cahan MD, Jonathan Frogel MD, Michael Arad MD, Haim Berkenstadt MD, and Rafael Kuperstein MD

Background: Pregnant women with Marfan syndrome (MS) have a high risk of aortic dissection around delivery and their optimal management requires a multi-disciplinary approach, including proper cardio-obstetric care and adequate pain management during labor, which may be difficult due to the high prevalence of dural ectasia (DE) in these patients.

Objectives: To evaluate the multidisciplinary management of MS patients during labor.

Methods: Nineteen pregnant women (31 pregnancies) with MS were followed by a multi-disciplinary team (cardiologist, obstetrician, anesthesiologist) prior to delivery.

Results:. Two patients had kyphoscoliosis; none had previous spine surgery nor complaints compatible with DE. In eight pregnancies (7 patients), aortic root diameter (ARd) before pregnancy was 40 to 46 mm. In this high-risk group, one patient underwent elective termination, two underwent an urgent cesarean section (CS) under general anesthesia, and five had elective CS; two under general anesthesia (GA), and three under spinal anesthesia. In 23 pregnancies (12 patients), ARd was < 40 mm. In this non-high-risk group three pregnancies (1 patient) were electively terminated. Of the remaining 20 deliveries (11 patients), 14 were vaginal deliveries, 9 with epidural analgesia and 5 without. Six patients had a CS; four under GA and two2 under spinal anesthesia. There were no epidural placement failures and no failed responses. There were 2 cases of aortic dissection, unrelated to the anesthetic management.

Conclusions: The optimal anesthetic strategy during labor in MS patients should be decided by a multi-disciplinary team. Anesthetic complications due to DE were not encountered during neuraxial block

August 2018
Anan Younis MD, Dov Freimark MD, Robert Klempfner MD, Yael Peled MD, Yafim Brodov MD, Ilan Goldenberg MD and Michael Arad MD

Background: Cardiac damage caused by oncological therapy may manifest early or many years after the exposure.

Objectives: To determine the differences between sub-acute and late-onset cardiotoxicity in left ventricular ejection fraction (LVEF) recovery as well as long-term prognosis.

Methods: We studied 91 patients diagnosed with impaired systolic function and previous exposure to oncological therapy. The study population was divided according to sub-acute (from 2 weeks to ≤ 1 year) and late-onset (> 1 year) presentation cardiotoxicity. Recovery of LVEF of at least 50% was defined as the primary end point and total mortality was the secondary end point.

Results: Fifty-three (58%) patients were classified as sub-acute, while 38 (42%) were defined as late-onset cardiotoxicity. Baseline clinical characteristics were similar in the two groups. The mean LVEF at presentation was significantly lower among patients in the late-onset vs. sub-acute group (28% vs. 37%, respectively, P < 0.001). Independent predictors of LVEF recovery were trastuzumab therapy and a higher baseline LVEF. Although long-term mortality rates were similar in the groups with sub-acute and late-onset cardiotoxicity, improvement of LVEF was independently associated with reduced mortality.

Conclusions: Our findings suggest that early detection and treatment of oncological cardiotoxicity play an important role in LVEF recovery and long-term prognosis.

November 2014
Michael Arad MD Msc, Lorenzo Monserrat MD PhD, Shiraz Haron-Khun MSc, Jonathan G. Seidman PhD, Christine E. Seidman MD, Eloisa Arbustini MD PhD, Michael Glikson MD and Dov Freimark MD

Background: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.

Objectives: To analyze the impact of genetic diagnosis on the clinical management of HCM.

Methods: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.

Results: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.

Conclusions: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determine the indication for genetic testing and interpretation of the results.

July 2014
Michael Arad MD, Tamar Nussbaum MD, Ido Blechman BA, Micha S. Feinberg MD, Nira Koren-Morag PhD,Yael Peled MD and Dov Freimark MD

Background: Contemporary therapies improve prognosis and may restore left ventricular (LV) size and function.

Objectives: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM).

Methods: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by ≥ 10% concomitant with ≥ 10% decreased LV end-diastolic dimension.

Results: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the RR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, lower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose was related to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01).

Conclusions: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures. 

July 2009
D. Freimark, M. Arad, S. Matetzky, I. DeNeen, L. Gershovitz, N. Koren Morag, N. Hochberg, Y. Makmal and M. Shechter

Background: Chronic heart failure is associated with excessive hospitalizations and poor prognosis.

Objectives: To summarize the 5 year experience of a single-center CHF[1] day care service, detect the cardiovascular and non-cardiovascular events, and evaluate the safety of the treatments provided.

Methods: We retrospectively studied all patients admitted to the CHF day care service of the Sheba Medical Center between September 2000 and September 2005.

Results: Advanced (New York Heart Association class III-IV) CHF patients (n=190), mean age 65 ± 12 years and left ventricular ejection fraction 25 ± 11%, were treated for 6 hourly biweekly visits; 77% had ischemic and 23% had non-ischemic cardiomyopathy. Treatment included: intravenous diuretic combinations (91%), intermittent low dose (≤ 5 mg/kg/min) dobutamine (87%), low dose (≤ 3 mg/kg/min) dopamine (38%), intravenous iron preparation and/or blood (47%), and intravenous nitropruside (36%). Follow-up of at least 1 year from initiation of therapy was completed in 158 of 190 patients (83%). Forty-six (29.3%) died: 23% due to CHF exacerbation, 5.7% from infection, 4.4% from sudden cardiac death, 3.8% from malignancy, 2.5% from malignant arrhythmias, 1.9% from renal failure, 1.3% from stroke, and 0.6% from myocardial infarction. There were only 0.68 rehospitalizations/patient/year; the most frequent cause being CHF exacerbation (16.5%).

Conclusions: Our study demonstrates the safety and potential benefits of a supportive day care service for advanced CHF patients. Multidrug intravenous treatment, accompanied by monitoring of electrolytes, hemoglobin and cardiac rhythm, along with education and psychological support, appear to reduce morbidity in advanced CHF patients and may have contributed to the lower than expected mortality/hospitalization rate.

[1] CHF = chronic heart failure

June 2005
M. Arad, H. Lahat and D. Freimark
 Familial cardiomyopathies represent a substantial portion of idiopathic dilated cardiomyopathy in clinical practice. Diversity of clinical presentations and variability in penetrance lead to under-recognition of this disease entity as an inherited disorder. The mechanisms by which mutations in different genes perturb cardiac function and lead to pathologic remodeling help understand the molecular pathways in disease pathogenesis and define the potential targets for therapeutic interventions. Appreciating when DCM[1] is inherited might spare unnecessary diagnostic efforts and, instead, help give appropriate attention to the timely detection of subclinically affected family members. Establishing preventive therapy in asymptomatic family members showing early signs of cardiac dysfunction might prevent death and slow down progression to end-stage heart failure.


[1] DCM = dilated cardiomyopathy

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