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עמוד בית
Mon, 07.10.24

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March 2010
O. Amir, O. Rogowski, M. David, N. Lahat, R. Wolff and B.S. Lewis

Background: Interleukin-10 is an anti-inflammatory cytokine and consequently is considered by many to have a protective role in heart failure, as opposed to the notorious tumor necrosis factor-alpha.

Objectives: To test the hypothesis of the possible beneficial impact of IL-10[1] on mortality in systolic heart failure patients in relation to their circulating TNFα[2] levels.

Methods: We measured circulating levels of IL-10 and TNFα in 67 ambulatory systolic heart failure patients (age 65 ± 13 years).

Results: Mortality was or tended to be higher in patients with higher levels (above median level) of circulating TNFα (9/23, 39% vs. 6/44, 14%; P = 0.02) or IL-10 (10/34, 30% vs. 5/33, 15%; P = 0.10). However, mortality was highest in the subset of patients with elevation of both markers above median (7/16, 44% vs. 8/51, 16%; P = 0.019). Elevation of both markers was associated with more than a threefold hazard ratio for mortality (HR[3] 3.67, 95% confidence interval 1.14–11.78).

Conclusions: Elevated circulating IL-10 levels in systolic heart failure patients do not have a protective counterbalance effect on mortality. Moreover, patients with elevated IL-10 and TNFα had significantly higher mortality, suggesting that the possible interaction in the complex inflammatory and anti-inflammatory network may need further study.

 






[1] IL = interleukin

[2] TNFα = tumor necrosis factor-alpha

[3] HR = hazard ratio


February 2008
O. Amir, H. Paz, R. Ammar, N. Yaniv J.E. Schliamser and B.S. Lewis
 
Background: Serum natriuretic peptide levels are useful diagnostic and prognostic markers in patients with acute decompensated heart failure, but have been little used to stratify urgency of treatment in the outpatient situation.

Objectives: To examine the use of natriuretic peptide to guide priority of patient referral to a heart failure center.

Methods: We analyzed data from 70 consecutive patients with chronic heart failure (NYHA class 2-4) referred for first evaluation in a specialized outpatient heart failure center. Serum NT-proBNP[1] was measured at the initial patient visit. We examined correlates and predictive value of mid- and upper tertile NT-proBNP for mortality in comparison with other known prognostic indicators using univariate and multivariate logistic regression analysis.

Results: Mortality at 6 months was 26.0% in patients with upper tertile (> 1958 pg/ml) NT-proBNP, 8.7% in the middle tertile group and 0% in the lowest tertile (P = 0.017). Patients with upper tertile serum NT-proBNP levels (group 3) had lower left ventricular ejection fraction, were more often in atrial fibrillation (P = 0.04) and more often had renal failure (P = 0.03). Age-adjusted logistic regression analysis identified upper tertile serum NT-proBNP level as the strongest independent predictor of 6 month mortality with a sixfold risk of early death (adjusted odds ratio 6.08, 95% confidence interval 1.58–47.13, P = 0.04). NT-proBNP was a more powerful predictor of prognosis than ejection fraction and other traditional outcome markers.

Conclusions: In heart failure patients referred to an outpatient specialized heart failure center, an upper tertile NT-proBNP level identified patients at high risk for mortality. A single high > 550 pg/ml NT-proBNP measurement appears to be useful for selecting patients for care in a heart failure center, and a level > 2000 pg/ml for assigning patients to high priority management.






[1] NT-proBNP = - N-terminal pro-brain natriuretic peptide


December 2007
April 2007
M. Garty, A. Shotan, S. Gottlieb, M. Mittelman, A. Porath, B.S. Lewis, E. Grossman, S. Behar, J. Leor, M. S. Green, R. Zimlichman and A. Caspi

Background: Despite improved management of heart failure patients, their prognosis remains poor.

Objectives: To characterize hospitalized HF[1] patients and to identify factors that may affect their short and long-term outcome in a national prospective survey.

Methods: We recorded stages B-D according to the American College of Cardiology/American Heart Association definition of HF patients hospitalized in internal medicine and cardiology departments in all 25 public hospitals in Israel.

Results: During March-April 2003, 4102 consecutive patients were recorded. Their mean age was 73 ± 12 years and 57% were males; 75.3% were hypertensive, 50% diabetic and 59% dyslipidemic; 82% had coronary artery disease, 33% atrial fibrillation, 41% renal failure (creatinine ³ 1.5 mg/dl), and 49% anemia (hemoglobin £ 12 g/dl). Mortality rates were 4.7% in-hospital, 7.6% at 30 days, 18.7% at 6 months and 28.1% at 12 months. Multiple logistic regression analysis revealed that increased 1 year mortality rate was associated with New York Heart Association III–IV (odds ratio 2.07, 95% confidence interval 1.78–2.41), age (for 10 year increment) (OR[2] 1.41, 95% CI[3] 1.31–1.52), renal failure (1.79, 1.53–2.09), anemia (1.50, 1.29–1.75), stroke (1.50, 1.21–1.85), chronic obstructive pulmonary disease (1.25, 1.04–1.50) and atrial fibrillation (1.20, 1.02–1.40).

Conclusions: This nationwide heart failure survey indicates a high risk of long-term mortality and the urgent need for the development of more effective management strategies for patients with heart failure discharged from hospitals.

 







[1] HF = heart failure



[2] OR = odds ratio



[3] CI = confidence interval


B. S. Lewis, A. Shotan, S. Gottlieb, S. Behar, D. A. Halon, V. Boyko, J. Leor, E. Grossman, R. Zimlichman, A. Porath, M. Mittelman, A. Caspi and M. Garty

Background: Heart failure with preserved systolic left ventricular function is a major cause of cardiac disability.

Objectives: To examine the prevalence, characteristics and late clinical outcome of patients hospitalized with HF-PSF[1] on a nationwide basis in Israel.

Methods: The Israel nationwide HF survey examined prospectively 4102 consecutive HF patients admitted to 93 internal medicine and 24 cardiology departments in all 25 public hospitals in the country. Echocardiographic LV function measurements were available in 2845 patients (69%). The present report relates to the 1364 patients who had HF-PSF (LV ejection fraction ≥ 40%).

Results: Mortality of HF-PSF patients was high (in-hospital 3.5%, 6 months 14.2%, 12 months 22.0%), but lower than in patients with reduced systolic function (all P < 0.01). Mortality was higher in patients with HF as the primary hospitalization diagnosis (16.0% vs. 12.5% at 6 months, P = 0.07 and 26.2% vs. 18.0% at 12 months, P = 0.0002). Patients with HF-PSF who died were older (78 ± 10 vs. 71 ± 12 years, P < 0.001), more often female (P = 0.05) and had atrial fibrillation more frequently (44% vs. 33%, P < 0.01). There was also a relationship between mortality and pharmacotherapy: after adjustment for age and co-morbid conditions, mortality was lower in patients treated with angiotensin-converting enzyme inhibitors (P = 0.0003) and angiotensin receptor blockers (P = 0.002) and higher in those receiving digoxin (P = 0.003) and diuretic therapy (P = 0.009).

Conclusions: This nationwide survey highlights the very high late mortality rates in patients hospitalized for HF without a decrease in systolic function. The findings mandate a focus on better evidence-based treatment strategies to improve outcome in HF-PSF patients.

 







[1] HF-PSF = heart failure with preserved systolic left ventricular function


A. Shiran, S. Adawi, I. Dobrecky-Mery, D. A. Halon, and Basil S. Lewis

Background: Echocardiographic ventricular function predicts prognosis and guides management in patients with acute coronary syndromes. In elderly patients, interpretation of echocardiographic measurements may be difficult, especially regarding assessment of diastolic left ventricular function.

Objectives: To examine the usefulness of echocardiographic systolic and echocardiographic diastolic LV[1] function measurements as predictors of long-term outcome in elderly patients with ACS[2].

Methods: We studied 142 consecutive elderly patients (≥ 70 years old, mean age 80 ± 6 years) with ACS who had an echocardiogram at index hospitalization and were in sinus rhythm. LV ejection fraction and diastolic mitral inflow pattern were examined as predictors of survival and repeat hospitalization over a period of 18–24 months.

Results: During the 2 year mean follow-up period 35/142 patients died (25%). Survival was lower in patients with EF[3] < 40% (n=42) as compared to EF ≥ 40% (n=100) (2 year survival rate 61% vs. 81%, P = 0.038). Patients with severe diastolic dysfunction (a restrictive LV filling pattern, n=7) had a lower survival rate than those without (43 vs. 76%, P = 0.009). The most powerful independent predictor of mortality was a restrictive filling pattern (hazard ratio 4.6, 95% confidence interval 1.6–13.5), followed by a clinical diagnosis of heart failure on admission and older age. Rate of survival free of repeat hospitalization was low (33% at 18 months) but repeat hospitalization was not predicted either by EF or by a restrictive filling pattern.

Conclusions: As in the young, echocardiographic measurements of systolic and diastolic LV function predicted long-term survival in elderly patients with ACS. A restrictive filling pattern was the strongest independent predictor of mortality.

 







[1] LV = left ventricular

[2] ACS = acute coronary syndromes

[3] EF = ejection fraction


S. Alroy, M. Preis, M. Barzilai, A. Cassel, L. Lavie, D. A. Halon, O. Amir, B. S. Lewis and M. Y. Flugelman

Background: The etiology of chest pain with normal epicardial coronary arteries (cardiac syndrome X) seems to be related to endothelial cell dysfunction. Multiple factors are implicated in the pathophysiology, including evelated levels of homocysteine in the blood. Mutations in the MTHFR gene are associated with evelated levels of homocysteine.

Objectives: To test whether abnormal homocysteine metabolism is associated with syndrome X.

Methods: Forty-two women with chest pain, positive stress test and normal coronary arteries (syndrome X) and 100 asymptomatic women (controls) were studied for the C677T mutation. Vitamin B12, folic acid, and plasma levels of homocysteine were also measured. Endothelial cell function was studied in 10 patients with syndrome X and homozygosity for C677T mutation, and in 10 matched healthy controls. Folic acid (5 mg daily) was prescribed to syndrome X patients after initial measurements of ECF[1]. Following 13 weeks of treatment, ECF and blood tests were repeated and compared to baseline measurements.

Results: Homozygosity for C677T mutation was doubled in syndrome X vs. control (33%, 14/42 vs. 16%, 16/100, P < 0.02), and homocysteine levels were increased (9.16 ± 2.4 vs. 8.06 ± 2.6 μmol/L, P = 0.02). In the 10 homozygous patients, homocysteine levels decreased significantly after treatment with 5 mg/day folic acid (10 ± 3.3 vs. 5.4 ± 1.1 µmol/L, P = 0.004). Abnormal baseline ECF improved after treatment with folic acid: flow-mediated dilatation was greater (11.3 ± 7.9% vs. 0.7 ± 4.5%, P < 0.002), as was nitroglycerin-mediated dilatation (15.2 ± 9.0% vs. 5.6 ± 6.4%, P < 0.003). Frequency of chest pain episodes was significantly reduced after 13 weeks of folic acid treatment.

Conclusion: Our findings establish the association between the C677T mutation, endothelial cell dysfunction and cardiac syndrome X, and provide a novel and simple therapy for a subset of patients with syndrome X and homozygosity for the C677T mutation.






[1] ECF = endothelial cell function



 
December 2006
A. Jotkowitz, A. Porath, A. Shotan, M. Mittelman, E. Grossman, R. Zimlichman, B.S. Lewis, A. Caspi, S. Gottlieb and M. Garty, for the Steering Committee of the Israeli Heart Failure National Survey 2003

Background: Despite significant advances in the therapy of heart failure, many patients still do not receive optimal treatment.

Objectives: To document the standard of care that patients hospitalized with HF[1] in Israel received during a 2 month period.

Methods: The Heart Failure Survey in Israel 2003 was a prospective 2 month survey of patients admitted to all 25 public hospitals in Israel with a diagnosis of HF.

Results: The mean age of the 4102 patients was 73 years and 43% were female. The use of angiotensin-converting enzyme/angiotensin receptor blockers and beta blockers both declined from NYHA class I to IV (68.8% to 50.6% for ACE[2]-inhibitor/ARB[3] and 64.1% to 52.9% for beta blockers, P < 0.001 for comparisons). The percentage of patients by NYHA class taking an ACE-inhibitor or ARB and a beta blocker at hospital discharge also declined from NYHA class I to IV (47.5% to 28.8%, P < 0.002 for comparisons). The strongest predictor of being discharged with an ACE-inhibitor or ARB was the use of these medications at hospital admission. Negative predictors for their usage were age, creatinine, disease severity class, and functional status.

Conclusions: Despite the dissemination of guidelines many patients did not receive optimal care for HF. Reasons for this discrepancy need to be identified and modified.






[1] HF = heart failure



[2] ACE = angiotensin-converting enzyme



[3] ARB = angiotensin receptor blocker


May 2006
R. Rubinshtein, D.A. Halon, A. Kogan, R. Jaffe, B. Karkabi, T. Gaspar, M.Y. Flugelman, R. Shapira, A. Merdler and B.S. Lewis

Background: Emergency room triage of patients presenting with chest pain syndromes may be difficult. Under-diagnosis may be dangerous, while over0diagnosis may be costly.

Objectives: To report our initial experience with an emergency room cardiologist-based chest pain unit in Israel.

Methods: During a 5 week pilot study, we examined resource utilization and ER [1] diagnosis in 124 patients with chest pain of uncertain etiology or non-high risk acute coronary syndrome. First assessment was performed by the ER physicians and was followed by a second assessment by the CPU[2] team. Assessment was based on the following parameters: medical history and examination, serial electrocardiography, hematology, biochemistry and biomarkers for ACS[3], exercise stress testing and/or 64-slice multi-detector cardiac computed tomography angiography. Changes in decision between initial assessment and final CPU assessment with regard to hospitalization and utilization of resources were recorded.

Results: All patients had at least two cardiac troponin T measurements, 19 underwent EST[4], 9 echocardiography and 29 cardiac MDCT[5]. Fourteen patients were referred for early cardiac catheterization (same/next day). Specific working diagnosis was reached in 71/84 patients hospitalized, including unstable angina in 39 (31%) and non-ST elevation myocardial infarction in 12 (10%). Following CPU assessment, 40/124 patients (32%) were discharged, 49 (39%) were admitted to Internal Medicine and 35 (28%) to the Cardiology departments. CPU assessment and extended resources allowed discharge of 30/101 patients (30%) who were initially identified as candidates for hospitalization after ER assessment. Furthermore, 13/23 (56%) of patients who were candidates for discharge after initial ER assessment were eventually hospitalized. Use of non-invasive tests was significantly greater in patients discharged from the ER (85% vs. 38% patients hospitalized) (P < 0.0001). The mean ER stay tended to be longer (14.9 ± 8.6 hours vs. 12.9 ± 11, P = NS) for patients discharged. At 30 days follow-up, there were no adverse events (myocardial infarction or death) in any of the 40 patients discharged from the ER after CPU assessment. One patient returned to the ER because of chest pain and was discharged after re-assessment. 

Conclusions: Our initial experience showed that an ER cardiologist-based chest pain unit improved assessment of patients presenting to the ER with chest pain, and enhanced appropriate use of diagnostic tests prior to decision regarding admission/discharge from the ER.


 




[1] ER = emergency room

[2] CPU = chest pain unit

[3] ACS = acute coronary syndrome

[4] EST = exercise stress testing

[5] MDCT = multi-detector cardiac computed tomography angiography


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