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עמוד בית
Sun, 26.05.24

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July 2020
Osnat Itzhaki Ben Zadok MD MSc, Daniel Murninkas MD, Zaza Iakobishvili MD PhD, Henri Jino MD, Esther Yohananov RN, Shlomo Birkenfeld MD and David Hasdai MD

Background: Heart failure (HF) patients with reduced ejection fraction (HFrEF) are frequently treated with sub-optimal doses of angiotensin converting enzyme-inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta blockers (BBs).

Objectives: To determine factors associated with attaining upper-range doses in patients with HFrEF.

Methods: We examined treatment in patients with left ventricular ejection fraction (LVEF) ≤ 40% in a community-based, dedicated heart-failure clinic. Upper-range doses were defined as ≥ 75% of target recommended doses by heart failure society guidelines.

Results: The majority of the 215 patients were men (82%); median age at presentation 73 years (interquartile range [IQR] 65–78) and LVEF of 30% (IQR 25–35%). Following the up-titration program, 41% and 35% of patients achieved upper-range doses of ACE-Is/ARBs and BBs, respectively. Higher body mass index (BMI) was the only parameter found to be associated with achieving upper-range doses of ACE-I/ARBs (odds ratio [OR] 1.13, 95% confidence interval [95%CI] 1.05–1.22, P = 0.001). More patients achieved this target as BMI increased, with a sharp decline in the highest obesity category (BMI ≥ 40 m2/kg). Attaining upper-range doses of BBs was associated with pre-existing diabetes mellitus (DM) (OR 2.6, 95%CI 1.34–5.19, P = 0.005); women were associated with attaining lower BBs doses (OR 0.34, 95%CI 0.13–0.90, P = 0.031).

Conclusions: Achieving upper-range doses of ACE-Is/ARBs and BBs in HFrEF outpatients in a treatment up-titration program were associated with greater BMI and DM, respectively. These findings may serve as benchmarks for up-titration programs.

February 2016
Shirit Kazum MD, Alon Eisen MD, Eli I. Lev MD, Zaza Iakobishvili MD, Alejandro Solodky MD, David Hasdai MD, Ran Kornowski MD and Aviv Mager MD

Background: Concomitant carotid artery disease (CaAD) in patients with coronary artery disease (CAD) is associated with worse cardiac and neurologic outcomes. The reported prevalence and risk factors for concomitant CaAD in CAD patients varied among previous studies. 

Objectives: To examine these factors in ambulatory patients with CAD and well-documented cholesterol levels treated with cholesterol-lowering medications. 

Methods: We retrospectively analyzed prospectively collected data from 325 unselected patients with CAD (89 women, mean age 68.8 ± 9.9 years) undergoing routine evaluation at the coronary clinic of our hospital. 

Results: The low density lipoprotein-cholesterol (LDL-C) was < 100 mg/dl in 292 patients (90%). Age at onset of CAD symptoms was 59.4 ± 10.8 years. Carotid stenosis ≥ 50% was seen in 83 patients (25.5%) and between 30% and 49% in 55 patients (17%) (duplex method). Carotid stenosis was significantly associated with hypertension (P = 0.032), peripheral arterial disease (P = 0.002) and number of coronary arteries with ≥ 50% stenosis (P = 0.002), and showed a borderline association with age at CAD onset (P = 0.062) and diabetes mellitus (P = 0.053). On linear regression analysis, independent predictors of CaAD were peripheral vascular disease (OR 3.186, 95%CI 1.403–7.236, P = 0.006), number of coronary arteries with ≥ 50% stenosis (OR 1.543, 95%CI 1.136–2.095, P = 0.005), and age at CAD onset (OR 1.028, 95%CI 1.002–1.054, P = 0.003). None of the variables studied predicted freedom from CaAD. 

Conclusions: Carotid atherosclerosis is very common in stable ambulatory patients with CAD regularly taking statins. The risk is higher in patients with peripheral arterial disease, a greater number of involved coronary arteries, and older age at onset of CAD. 

 

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. 

 

January 2014
Alon Eisen, Eli Lev, Zaza Iakobishvilli, Avital Porter, David Brosh, David Hasdai and Aviv Mager
Background: Treatment with HMG-CoA reductase inhibitors (statins) is often complicated by muscle-related adverse effects (MAEs). Studies of the association between low plasma vitamin D levels and MAEs have yielded conflicting results.

Objectives: To determine if low plasma vitamin D level is a risk factor for MAEs in statin users.

Methods: Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007–2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database.

Results: The sample included 272 patients (141 men) aged 33–89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 ± 20.5 vs. 44.7 ± 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 11 patients (4%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 ± 17.7 vs. 48.9 ± 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 ± 14.6 vs. 47.8 ± 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 ± 15.0 vs. 47.8 ± 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L).

Conclusions: There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.

July 2008
A. Mager, N. Koren-Morag, M. Shohat, A. Dadashev, R. Kornowski, A. Battler and D. Hasdai

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.






[1] CAD = coronary artery disease

[2] CI = confidence interval

[3] OR = odds ratio


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