Israel Medical Association Journal

Background: Endocardial leads of permanent pacemakers (PPM) and implantable defibrillators (ICD) across the tricuspid valve (TV) can lead to tricuspid regurgitation (TR) or can worsen existing TR with subsequent severe morbidity and mortality.

Objectives: To evaluate prospectively the efficacy of intraprocedural 2-dimentional-transthoracic echocardiography (2DTTE) in reducing/preventing lead-associated TR.

Methods: We conducted a prospective randomized controlled study comparing echocardiographic results in patients undergoing de-novo PPM/ICD implantation with intraprocedural echo-guided right ventricular (RV) lead placement (Group 1, n=56) versus non-echo guided implantation (Group 2, n=55). Lead position was changed if TR grade was more than baseline in Group 1. Cohort patients underwent 2DTTE at baseline and 3 and/or 6 months after implantation. Excluded were patients with baseline TR > moderate or baseline ≥ moderate RV dysfunction.

Results: The study comprised 111 patients (74.14 ± 11 years of age, 58.6% male, 19% ICD, 42% active leads). In 98 patients there was at least one follow-up echo. Two patients from Group 1 (3.6%) needed intraprocedural RV electrode repositioning. Four patients (3.5%, 2 from each group, all dual chamber PPM, 3 atrial fibrillation, 2 RV pacing > 40%, none with intraprocedural reposition) had TR deterioration during 6 months follow-up. One patient from Group 2 with baseline mild-moderate aortic regurgitation (AR) had worsening TR and AR within 3 months and underwent aortic valve replacement and TV repair.

Conclusions: The rate of mechanically induced lead-associated TR is low; thus, a routine intraprocedural 2DTTE does not have a significant role in reducing/preventing it

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06–5.62; P = 0.036) for patients with moderate-severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease with the presence of autoantibodies, rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA). The presence of RF or ACPA predicts RA severity. Data on the influence of ACPA titer on RA course are limited.

Objectives: To determine the correlation between ACPA titers at the time of RA diagnosis to RA features and severity during 3 years of follow-up.

Methods: We performed a retrospective study of RA patients treated at our institution during the years 2006–2015 with known ACPA titers at RA diagnosis who completed at least 3 years of follow-up. Patients (N=133) were divided according to ACPA titer: seronegative (< 15 U/ml, n=55), weakly positive (15–49 U/ml, n=18), moderately positive (50–300 U/ml, n=29), and strongly positive (> 300 U/ml, n=31). Patient data, including disease activity score (DAS28), bone erosion on hand and/or foot X-rays, treatments with corticosteroids and disease-modifying-anti-rheumatic drugs (DMARDs), and hospitalizations, were recorded. Chi-square and Mann-Whitney method were used for statistical analysis. P < 0.05 was considered as statistically significant.

Results: Male gender, smoking, and RF positivity correlated with ACPA positivity and higher ACPA titers. There was no correlation between ACPA titer and the variables defined as representing RA severity: higher DAS28, bone erosions, hospitalizations, need for corticosteroids, and conventional and biological DMARDs.

Conclusions: Titer of ACPA was not identified as a predictive factor for RA severity

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI), and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR as well as the relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%, P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (2.44, 95% confidence interval 1.06–5.6, P = .036) for patients with moderate to severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate to severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited.

Objectives: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban.

Methods: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence.

Results: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding.

Conclusions: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.

Background: During the coronavirus disease-2019 (COVID-19) pandemic outbreak our blood bank developed protocols to guarantee accurate blood components to COVID-19 patients.

Objectives: To provide convalescent whole blood donor screening strategies for patients recovering from COVID-19.

Methods: We recruited COVID-19 recovering patients who met our defined inclusion criteria for whole blood donation. All blood units were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA by real time reverse transcription polymerase chain reaction (RT-PCR) and SARS-COV-2 immunoglobulin G (IgG) antibodies against the S1 domain.

Results: We screened 180 blood units from patients recovering from COVID-19. All results were negative for SARS-CoV-2 RNA and 87.2% were positive for SARS-COV-2 IgG antibodies in the plasma.

Conclusions: Blood component units from recovering COVID-19 patients are safe. Plasma units with positive IgG antibodies could serve as an efficient passive immunization for COVID-19 patients. Moreover, in the face of increased transfusion demand for treatment of anemia and coagulation dysfunction in critical ill COVID-19 patients, red blood cells units and random platelets units from convalescent donors can be safely transfused.

Background: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.

Objectives: To evaluate SC tocilizumab in a real-life clinical setting.

Methods: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed.

Results: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively.

Conclusions: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.

Background: Behçet's disease is a multi-systemic chronic relapsing inflammatory disease, classified among the vasculitides. The heterogeneity of clinical manifestations challenges the disease management.

Objectives: To assess efficacy and safety of adalimumab in patients with active persistent Behçet's arthritis who did not respond to disease-modifying anti-rheumatic drugs and to assess the impact of treatment on the cytokine milieu.

Methods: Our cohort comprised 10 patients with active arthritis who received adalimumab in a 24-week investigator-initiated prospective open-label study. Patients who relapsed within 12 weeks following adalimumab discontinuation could enter a 3-year extension study. The patients underwent a comprehensive assessment including questionnaires and measurement of inflammatory cytokines, adalimumab serum levels, and anti-drug antibodies.

Results: A significant improvement was observed in arthritis, disease activity visual analogue scales, Behçet's disease current activity form, and interleukin-6 (IL-6) levels, but not in health assessment questionnaire and functional assessment of chronic illness therapy fatigue scale questionnaire. Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. The disease relapsed in 9 of 10 patients, within 2–6 weeks following adalimumab discontinuation. Of the 7 patients who continued the study, arthritis was resolved in 5. Two patients with high neutralizing antidrug antibodies titer relapsed.

Conclusions: Adalimumab treatment achieved a significant improvement in arthritis, mucocutaneous manifestations, and IL-6 levels in all study patients but only 40% reported significant pain reduction. The arthritis relapsed in 90% of patients following adalimumab discontinuation and long-term treatment was required.

Background: The effect of repeated intravenous amantadine (IVAM) in advanced Parkinsonism has not been studied in depth.

Objectives: To report the experience of our medical center with repeated IVAM infusions in patients with advanced Parkinsonism.

Methods: Thirty patients with advanced Parkinsonism of various etiologies were enrolled in an open-label retrospective study. All patients were treated with IVAM infusions in a neurological daycare center. Treatment was initiated with a loading dose of 200/400 mg per day for 5 days followed by a once-daily maintenance dose of 200/400 mg every 1 to 3 weeks. Patients and their caregivers participated in a structured interview and independently completed a clinical global impression of changes scale questionnaire on various motor and non-motor symptoms.

Results: Patient mean age was 73.3 ± 9.7 years, average disease duration was 6.2 ± 5.7 years, and mean Hoehn and Yahr score was 3.2 ± 0.84. Mean duration of the IVAM treatment was 15.1 ± 11.6 months. An improvement in general function was reported by 91% of the patients and 89% of the caregivers. Most of the patients reported improvement in tremor and rigidity, as well as in gait stability, freezing of gait, and reduced falls. The treatment was safe with few side effects.

Conclusions: Our data suggest that repeated IVAM infusions could be an effective treatment against various motor symptoms and for improvement of mobility in patients with advanced Parkinsonism. Further randomized clinical trials with a larger sample size using objective measures are warranted to validate our results.

Background: The MitraClip procedure is becoming an acceptable alternative for high-risk patients with mitral regurgitation (MR) due to functional (FMR) or degenerative (DMR) disease and suitable mitral anatomy.

Objectives: To evaluate the results of MitraClip at our institute in carefully selected patients.

Methods: We conducted a retrospective analysis of medical records and echocardiography data from January 2012 to December 2017.

Results: A total of 39 MitraClip procedures in 37 patients (aged 75 ± 12 years, 9 women) was performed. Twenty-four patients presented with FMR, 12 with DMR, and 1 with combined pathology. One-day post-procedure MR was moderate to low in 86.1% of patients, with immediate device success in 88.8%. MR at 1 year was moderate to low in 79% at 1 year. Survival at 1 year was 86% and at 2 years 69.4%. Peri-procedural (< 1 week) death and MitraClip failure occurred in one and three patients, respectively. New York Heart Association score improved to class 1 or 2 in 37% of patients at 1 year vs. one patient at baseline. Post-procedural systolic pulmonary pressure was reduced from 53 (range 48–65) to 43 (range 36–52) mmHg at 1 month with a subsequent plateau at follow-up, to 41 (34–57) mmHg at 6 months, and to 47 (38–50) at 12 months.

Conclusions: MitraClip in severe MR resulted in modest improvement in functional status and pulmonary pressure with a small risk of immediate procedural complications. Outcomes are encouraging considering the natural course of MR and the risks of surgical intervention.