Offer Amir

Serum levels of microRNAs in patients with heart failure

Diagnosis and risk stratification of patients with heart failure remain a challenge. The small non‐coding RNAs known as microRNAs regulate gene expression and seem to play an important role in the pathogenesis of heart failure. In the current study, we aim to characterize the levels of microRNAs in the sera of chronic systolic heart failure patients vs. controls and assess the possible correlation between elevation in the levels of specific microRNAs and clinical prognostic parameters in heart failure patients.

The ACE deletion allele is associated with Israeli elite endurance athletes

An Alu insertion (I)/deletion (D) polymorphism in the angiotensin I converting enzyme (ACE) gene has been associated with ACE activity. Opposing effects on elite athletic performance have been proposed for the I and D alleles; while the D allele favours improved endurance ability, the I allele promotes more power‐orientated events. We tested this hypothesis by determining the frequency of ACE ID alleles amongst 121 Israeli top‐level athletes classified by their sporting discipline (marathon runners or sprinters). Genotyping for ACE ID was performed using polymerase chain reaction on DNA from leucocytes. The ACE genotype and allele frequencies were compared with those of 247 healthy individuals. Allele and genotype frequencies differed significantly between the groups. The frequency of the D allele was 0.77 in the marathon runners, 0.66 in the control subjects (P= 0.01) and 0.57 in the sprinters (P= 0.002). The ACE DD genotype was more prevalent among the endurance athletes (0.62) than among the control subjects (0.43, P= 0.004) and the power athletes (0.34, P= 0.004). In the group of elite athletes, the odds ratio of ACE DD genotype being an endurance athlete was 3.26 (95% confidence interval 1.49–7.11), and of ACE II genotype was 0.41 (95% confidence interval 0.14–1.19). We conclude that in Israeli elite marathon runners the frequency of the ACE D allele and ACE DD genotype seems to be higher than in sprinters, suggesting a positive association between the D allele and the likelihood of being an elite endurance athlete in some ethnic groups.

Human, Environmental & Exercise: The ACE deletion allele is associated with Israeli elite endurance athletes

An Alu insertion (I)/deletion (D) polymorphism in the angiotensin I converting enzyme (ACE) gene has been associated with ACE activity. Opposing effects on elite athletic performance have been proposed for the I and D alleles; while the D allele favours improved endurance ability, the I allele promotes more power‐orientated events. We tested this hypothesis by determining the frequency of ACE ID alleles amongst 121 Israeli top‐level athletes classified by their sporting discipline (marathon runners or sprinters). Genotyping for ACE ID was performed using polymerase chain reaction on DNA from leucocytes. The ACE genotype and allele frequencies were compared with those of 247 healthy individuals. Allele and genotype frequencies differed significantly between the groups. The frequency of the D allele was 0.77 in the marathon runners, 0.66 in the control subjects (P= 0.01) and 0.57 in the sprinters (P= 0.002). The ACE DD genotype was more prevalent among the endurance athletes (0.62) than among the control subjects (0.43, P= 0.004) and the power athletes (0.34, P= 0.004). In the group of elite athletes, the odds ratio of ACE DD genotype being an endurance athlete was 3.26 (95% confidence interval 1.49–7.11), and of ACE II genotype was 0.41 (95% confidence interval 0.14–1.19). We conclude that in Israeli elite marathon runners the frequency of the ACE D allele and ACE DD genotype seems to be higher than in sprinters, suggesting a positive association between the D allele and the likelihood of being an elite endurance athlete in some ethnic groups.

IL6 (-174) and TNFA (-308) promoter polymorphisms are associated with systemic creatine kinase response to eccentric exercise

Exertional rhabdomyolysis is a complex and poorly understood entity. The inflammatory system has an important role in muscle injury and repair. Serum creatine kinase (CK) is often used as systemic biomarker representing muscle damage. Considerable variation exists in CK response between different subjects. Genetic elements may act as predisposition factors for exertional srhabdomyolysis. Based on their biological activity, we hypothesized that in healthy subjects IL6 G-174C and TNFA G-308A promoter polymorphisms would be associated with CK response to exercise. We determined serum CK activity pre- and post-maximal eccentric contractions of the elbow flexor muscles. IL6 G-174C and TNFA G-308A genotypes were analyzed for possible relationship with changes in serum CK activity. IL6 G-174C genotype was associated with CK activity in a Dose-Dependent fashion. Subjects with one or more of the -174C allele had a greater increase and higher peak CK values than subjects homozygous for the G allele (meanxa0±xa0SE U/L: GG, 2,604xa0±xa0821; GC, 7,592xa0±xa01,111; CC, 8,403xa0±xa03,849, ANOVA Pxa0=xa00.0003 for GGxa0+xa0GC genotypes versus CC genotype, Pxa0=xa00.0005 for linear trend). IL6-174CC genotype was associated with a greater than threefold increased risk of massive CK response (adjusted odds ratio 3.29, 95% confidence interval 1.27–7.85, Pxa0=xa00.009). A milder association (Pxa0=xa00.06) was noted between TNFA G-308A genotype and CK activity. In conclusion, we found a strong association of the IL6 G-174C genotype with systemic CK response to strenuous exercise. Data suggest that homozygosity for the IL6-174C allele is a clinically important risk factor for exercise-induced muscle injury, further supporting the central role of cytokines in the reactive inflammatory process of muscle damage and repair.

Organization of heart failure management in European Society of Cardiology member countries: Survey of the Heart Failure Association of the European Society of Cardiology in collaboration with the Heart Failure National Societies/Working Groups

The aim of this document was to obtain a real‐life contemporary analysis of the demographics and heart failure (HF) statistics, as well as the organization and major activities of the Heart Failure National Societies (HFNS) in European Society of Cardiology (ESC) member countries.

Aldosterone Synthase Gene Polymorphism as a Determinant of Atrial Fibrillation in Patients With Heart Failure

We analyzed the possible association between aldosterone synthase (CYP11B2) T-344C polymorphism, which is associated with increased aldosterone activity, and the prevalence of atrial fibrillation (AF) in 196 consecutive patients who had symptomatic systolic heart failure (HF; left ventricular ejection fraction <40%) for > or =3 months before recruitment. Genomic DNA was extracted from peripheral blood leukocytes using a standard protocol. Subjects were genotyped for the CYP11B2 polymorphism using the polymerase chain reaction/restriction fragment length polymorphism approach. AF was present in 63 patients (33%) with HF. We found the -344 CC genotype to be a strong independent marker for AF. Almost 1/2 (45%) of patients with this genotype had AF compared with 1/4 (27%) with -344 TT and TC genotypes (p = 0.01). A multivariate stepwise logistic regression model that included age, gender, New York Heart Association class, CYP11B2 -344CC genotype, and echocardiographic measurements of left ventricular ejection fraction, left atrial dimension, left ventricular end-diastolic diameter, and mitral regurgitation severity showed that the CYP11B2 CC genotype (adjusted for age and left atrial size) was an independent predictor of AF (adjusted odds ratio 2.35, 95% confidence interval 1.57 to 3.51, p = 0.03). In conclusion, CYP11B2 T-344C promoter polymorphism predisposes to clinical AF in patients with HF.

Sildenafil in Heart failure (SilHF). An investigator-initiated multinational randomized controlled clinical trial: rationale and design.

Heart failure (HF) is a major clinical problem and, despite advances in both pharmacological and device therapy, the mortality remains high and quality of life poor. Over the last decade there has been growing interest in using phosphodiesterase‐5 (PDE‐5) inhibitors in HF associated with group 2 pulmonary hypertension (PH), with benefits reported on pulmonary haemodynamic and functional status in single‐centre trials

The association between obesity, mortality and filling pressures in pulmonary hypertension patients; the “obesity paradox”

BACKGROUNDnThe term obesity paradox, refers to lower mortality rates in obese patients, and is evident in various chronic cardiovascular disorders. There is however, only scarce data regarding the clinical implication of obesity and pulmonary hypertension (PH). Therefore, in the current study, we evaluated the possible prognostic implications of obesity in PH patients.nnnMETHODSnWe assessed 105 consecutive PH patients for clinical and hemodynamic parameters, focusing on the possible association between Body Mass Index (BMI) and mortality. Follow-up period was 19 ± 13 months.nnnRESULTSnSixty-one patients (58%) had pre-capillary PH and 39 patients (37%) out-of-proportion post-capillary PH. During follow-up period, 30 patients (29%) died. Death was associated with reduced functional-class, inverse-relation with BMI, higher pulmonary artery and right atrial pressures, pulmonary vascular resistance and signs of right ventricular failure. In multivariate analysis, obesity (BMI ≥ 30 kg/m²), was the variable most significantly correlated with improved survival [H.R 0.2, 95% C.I 0.1-0.6; p = 0.004], even after adjustment for baseline characteristics. Obese and very-obese (BMI ≥ 35 kg/m²) patients had significantly less mortality rates during follow-up (12% and 8%, respectively) than non-obese patients (41%), p = 0.01. The tendency of survival benefit for the obese vs. non-obese patients was maintained both in the pre-capillary (10% vs. 46% mortality, p = 0.008) and disproportional post-capillary PH patients (11% vs. 40% mortality, p = 0.04).nnnCONCLUSIONSnObesity was significantly associated with lower mortality in both pre-capillary and disproportional post-capillary PH patients. It seems that in PH, similarly to other chronic clinical cardiovascular disease states, there may be a protective effect of obesity, compatible with the obesity paradox.

Serum Oxidative Stress Level Correlates with Clinical Parameters in Chronic Systolic Heart Failure Patients

Serum oxidative stress (OS) level has an important role in the inflammatory process of heart failure.

Photoplethysmography as a single source for analysis of sleep-disordered breathing in patients with severe cardiovascular disease

Sleep‐disordered breathing and Cheyne–Stokes breathing are often not diagnosed, especially in cardiovascular patients. An automated system based on photoplethysmographic signals might provide a convenient screening and diagnostic solution for patient evaluation at home or in an ambulatory setting. We compared event detection and classification obtained by full polysomnography (the ‘gold standard’) and by an automated new algorithm system in 74 subjects. Each subject underwent overnight polysomnography, 60 in a hospital cardiology department and 14 while being tested for suspected sleep‐disordered breathing in a sleep laboratory. The sleep‐disordered breathing and Cheyne–Stokes breathing parameters measured by a new automated algorithm system correlated very well with the corresponding results obtained by full polysomnography. The sensitivity of the Cheyne–Stokes breathing detected from the system compared to full polysomnography was 92% [95% confidence interval (CI): 78.6–98.3%] and specificity 94% (95% CI: 81.3–99.3%). Comparison of the Apnea Hyponea Index with a cutoff level of 15 shows a sensitivity of 98% (95% CI: 87.1–99.6%) and specificity of 96% (95% CI: 79.8–99.3%). The detection of respiratory events showed agreement of approximately 80%. Regression and Bland–Altman plots revealed good agreement between the two methods. Relative to gold‐standard polysomnography, the simply used automated system in this study yielded an acceptable analysis of sleep‐ and/or cardiac‐related breathing disorders. Accordingly, and given the convenience and simplicity of its application, this system can be considered as a suitable platform for home and ambulatory screening and diagnosis of sleep‐disordered breathing in patients with cardiovascular disease.