Ivabradine: a new frontier in the treatment of stable coronary artery disease and chronic heart failure.

Ivabradine (IVA) is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. This pure heart rate-lowering agent possesses well-documented antianginal and anti-ischemic properties comparable to well-established antianginal agents, such as ß-blockers and calcium channel blockers. IVA lowers heart rate (HR) without affecting contractility or vascular tone and it is licensed for HR control in chronic heart diseases. The heart rate reduction is beneficial in patients with coronary artery disease (CAD), chronic stable angina pectoris, and chronic heart failure (CHF). Published trials documented not only pharmacodynamic and pharmacokinetic properties but also acceptable tolerance and safety profile of IVA, compared to other currently used cardiovascular drugs, including betablockers. The aim of this review is to describe recent evidences with IVA an interesting medicament, able to lower HR by selective inhibition of the If current, and to describe its applications.

Assessing viral taxonomic composition in benthic marine ecosystems: reliability and efficiency of different bioinformatic tools for viral metagenomic analyses.

In benthic deep-sea ecosystems, which represent the largest biome on Earth, viruses have a recognised key ecological role, but their diversity is still largely unknown. Identifying the taxonomic composition of viruses is crucial for understanding virus-host interactions, their role in food web functioning and evolutionary processes. Here, we compared the performance of various bioinformatic tools (BLAST, MG-RAST, NBC, VMGAP, MetaVir, VIROME) for analysing the viral taxonomic composition in simulated viromes and viral metagenomes from different benthic deep-sea ecosystems. The analyses of simulated viromes indicate that all the BLAST tools, followed by MetaVir and VMGAP, are more reliable in the affiliation of viral sequences and strains. When analysing the environmental viromes, tBLASTx, MetaVir, VMGAP and VIROME showed a similar efficiency of sequence annotation; however, MetaVir and tBLASTx identified a higher number of viral strains. These latter tools also identified a wider range of viral families than the others, providing a wider view of viral taxonomic diversity in benthic deep-sea ecosystems. Our findings highlight strengths and weaknesses of available bioinformatic tools for investigating the taxonomic diversity of viruses in benthic ecosystems in order to improve our comprehension of viral diversity in the oceans and its relationships with host diversity and ecosystem functioning.

Cardiac myxoma originating from areas of ventricular akinesia.

We present a case of large pedunculated myxoma (61×39 mm) in the left ventricular cavity with anterior-septal and anterior free wall akinesia. Angiographic study showed normal coronary arteries, but the clinical signs strongly suggested a previous myocardial infarction. We cannot exclude the possibility that the ventricular akinesia results from embolization of tumor fragments. For a time, cardiac myxomas were believed to arise from mural thrombi. In this case the presence of blood stasis or low-velocity blood flow related to wall motion abnormalities may have played a role in improving tumor growth.

Ivabradine improves quality of life in subjects with chronic heart failure compared to treatment with ß-blockers: results of a multicentric observational APULIA study.

OBJECTIVES: Ivabradine (IVA), a selective If current inhibitor decreasing the heart rate (HR) in patients with sinus rhythm, has been added to the most recent European Guidelines on heart failure. This selective treatment reduces HR exclusively while fully preserving myocardial contractility and relaxation, atrioventricular conduction, and ventricular repolarization, as well as blood pressure. The aim of this study was to evaluate the improvement of quality of life (QOL) in patients with chronic heart failure (CHF) treated with IVA versus two ß-blockers (bisoprolol and carvedilol). METHODS: We evaluated if a 1-month treatment with IVA (5 mg b.i.d.) or ß-blockers (carvedilol 6.25 mg b.i.d. or bisoprolol 1.25 mg b.i.d.) improves the QOL (assessed by SF-36 questionnaire) in patients with CHF with reduced left ventricular ejection fraction (<50%). SF-36 was tested in 221 CHF patients (mean age 64 ± 6 years) randomized into two groups (IVA group - 110 patients; ß-blockers group - 111 patients). Data of QOL questionnaire and HR were collected by an interview during a clinical visit both at prescription time (basal) and after 1 month of therapy with IVA or ß-blockers. QOL life and HR results after 1-month of therapy (T1) with IVA were compared with basal values (T0). RESULTS: The IVA versus ß-blockers treatment was associated with a significant improvement of physical functioning (p < 0.001 vs. p < 0.01), physical role functioning (p < 0.001 vs. p < 0.01), emotional role functioning (p < 0.01 vs. p < 0.85), and mental health scales (p < 0.001 vs. p < 0.01). HR in the IVA group was significantly lower compared to the group of patients treated with ß-blockers (63 vs. 67 bpm; p < 0.001). CONCLUSIONS: IVA treatment significantly improves the QOL in patients with CHF without any deleterious impact on hemodynamics, and may be beneficial in these patients without other adverse effects associated with ß-blockers.

Negative feedback interaction of HO-1/INOS in PBMC of acute congestive heart failure patients.

Heart failure (HF) is a common clinical syndrome with frequent exacerbations requiring hospitalization. Among the various mechanisms that underlie the pathogenesis of HF, the activation of the immune system leads to a progressive and redundant release of proinflammatory cytokines responsible for a variety of deleterious effects in heart failure, such as endothelial dysfunction, apoptosis of myocytes, activation of MMPs (Matrix Metallo Proteinases) and oxidative stress, with the result of decreased inotropism and clinical syndrome such as pulmonary edema,. The condition of oxidative stress induces the expression of genes coding for the proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). Twenty-five hospitalized cardiology patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction less than 35 percent) were included in the study. The aim of this study was to evaluate the cytokines plasma concentrations and the expression and activity of iNOS and HO-1 proteins in peripheral blood mononuclear cell (PBMC) extracted from patients in comparison to control group. In ACHF; left ventricular ejection fraction (LVEF) percent was reduced. Furthermore; iNOS and HO-1 expression and cytokines plasma levels were significantly higher in patients with ACHF as compared to controls group. Moreover the enzyme activity presents an opposite trend compared to that obtained in the analysis of the transcript and proteins. Our studies suggest a negative feedback interaction between iNOS and HO-1 important in the physiopathology of heart failure that could be considered a good candidate as a future therapeutic target for the development of new drugs.

Acute abdominal aortic thrombosis caused by paroxysmal atrial fibrillation.

Acute abdominal aortic thrombosis is a rare and potential fatal event, which occurs in adult subjects. We present the case of a 72-year-old-man, who referred to the emergency Department of our hospital because of persistent severe abdominal and perineal pain. Doppler ultrasounds and computerized tomography angiography revealed the acute thrombosis of the abdominal aorta. Immediate revascularization through aortic thrombo-endoarterectomy resolved the disease.

Ivabradine: the hope for a good treatment of ischemic heart disease.

Chronic stable angina pectoris (CSAP) is the most common manifestation of coronary artery disease (CAD). Angina pectoris occurs as a result of an imbalance between myocardial perfusion and the demands of the myocardium. Elevated heart rate (HR) is an important pathophysiological variable that increases myocardial oxygen demand, and also limits tissue perfusion by reducing the duration of diastole during which most myocardial perfusion occurs. Elevated resting HR represents a significant predictor of all-cause and cardiovascular mortality in the general population and patients with cardiovascular disease (CVD) because it assists the progression of CVD through the development of atherosclerosis, plaque destabilization, and initiation of arrhythmias. Since ß-blockers have been found to reduce HR, therefore, they are currently viewed as the first line therapy for CSAP and are associated with an improved prognosis after acute myocardial infarction (AMI) or congestive heart failure (CHF). The classical treatments for HR reduction have shown negative aspects, such as ß-blockers therapy which exerts negative effects on regional myocardial blood flow and function when HR reduction is eliminated by atrial pacing. Calcium channel antagonists functionally antagonize coronary vasoconstriction mediated through α-adrenoreceptors, and are thus devoid of this undesired effect, but the compounds are nevertheless negative inotrope. Ivabradine (IVA), a pure HR lowering drug, reduces the demand of myocardial oxygen during exercise, contributes to the restoration of oxygen balance and is therefore beneficial in chronic CVD. No relevant negative effects have been observed on cardiac conduction, contractility, relaxation, repolarization or blood pressure (BP). Beneficial effects of IVA have been noticed in CSAP and CHF, with optimal tolerability profile due to selective interaction with I(f) channel of sino atrial node cells. More recently, IVA has been highly recommended to be used in patients with CAD in association with ß-blockers. This review highlights the importance of IVA in the treatment of ischemic heart disease.

Ivabradine improves all aspects of quality of life assessed with the 36-item short form health survey in subjects with chronic ischemic heart disease compared with beta-blockers.

No published studies have evaluated quality of life (QOL) with the 36-item Short Form Health Survey (SF-36) in subjects with chronic stable angina pectoris (CSAP). We evaluated whether a 1-month treatment with 10 mg ivabradine (IVA) or ß-blockers (bisoprolol 2.5 mg/day, carvedilol 12.5 mg/day, atenolol 50 mg/day) improves the QOL in patients with CSAP. The SF-36 was administered to 238 patients randomized in two groups. QOL and heart rate (HR) results after 1 month of therapy with IVA and ß-blockers (T1) were compared with basal values (T0). Treatments in both groups significantly reduced HR (-11 bpm at T1 compared with T0 in the IVA group, -7 bpm at T1 compared with T0 in the ß-blocker group), but IVA demonstrated a more significant (p < 0.001) reduction in HR than ß-blocker treatment (p < 0.01). We observed a significant improvement in all QOL dimensions in the group treated with IVA, in particular in the sections regarding physical functioning, physical role, and general health (p < 0.001). In the group treated with ß-blockers, we found statistically significant improvement only in the physical functioning and physical role sections (p < 0.01). With ß-blocker treatment, many questionnaire sections showed no statistically significant improvement (body pain, social functioning, emotional role, and mental component summary). IVA treatment significantly improves all aspects of QOL in patients with CSAP, unlike ß-blocker treatment. This improvement is associated with a greater reduction in HR.

ADMA, SDMA, L-Arginine and nitric oxide in allergic pediatric bronchial asthma.

Published data regarding asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine (L-ARG) and nitric oxide fraction in exhaled air (FeNO) in pediatric bronchial asthma are limited. Many question remain open about plasma concentration of these substances. The aim of this study is to evaluate ADMA, SDMA, L-ARG and FeNO concentration in allergic pediatric mild asthmatic patients in respect to healthy subjects. In this case-control study 60 children (50 asthmatics and 10 healthy) underwent a complete clinical visit, baseline respiratory function, allergy tests and biochemical analyses. The statistical significance of the different concentrations between the two groups were studied using one-way analysis of variance (ANOVA). A p value less than 0.05 was considered statistically significant. The mean plasma ADMA (0.58 vs 0.68 micromol/L), SDMA (0.40 vs 0.45 micromol/L) and L-ARG (52.2 vs 74.13 micromol/L) concentration were significantly lower (p less than 0.001) in the asthmatic patients in respect to healthy subjects (control group). The concentration of FeNO was significantly higher in the asthmatic subjects in respect to the control group (9.18 vs 4.2 micromol/L; p less than 0.001). Low plasma concentrations of ADMA, SDMA, L-ARG and high concentration of FeNO are associated with bronchial asthma and indicate an important role in airway disease through NO metabolism.

Lycopene and preclinical carotid atherosclerosis.

Evidence from epidemiological and clinical studies suggests a possible correlation between serum antioxidant levels and cardiovascular disease risk. High plasma concentrations of lycopene have been associated with reduced prevalence of cardiovascular disease. The aim of this study is to compare plasma concentrations of lycopene in subjects with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. One hundred and twenty subjects underwent physical examination, ultrasonic measurement of common carotid artery intima-media thickness and serum profile analysis. Logistic regression methods and analysis of variance were used to determine whether differences existed between participants with or without evidence of carotid atherosclerosis. Of the 120 participants, 58 exhibited evidence of carotid atherosclerosis. Participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly higher serum concentrations of total cholesterol, LDL-cholesterol and triglycerides. In contrast, participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly lower plasma concentrations of lycopene. These data suggest that higher serum levels of lycopene may play a protective role versus cardiovascular diseases, in particular carotid atherosclerosis.

Recurrent atrial fibrillation in a patient with ulcerative colitis treated with azathioprine: case report and review of the literature.

We present a clinical case report regarding recurrent atrial fibrillation in a patient with ulcerative colitis treated with azathioprine. Atrial fibrillation represents the most common sustained cardiac arrhythmia, occurring in 1-2% of the general population and characterized by seemingly disorganized atrial depolarizations without effective atrial contraction. Several mechanisms determine this arrhythmia; in particular remodelling (structural, mechanical and electrical alteration related to atrial fibrillation). The pro-arrhythmic effect of azathioprine may be evaluated during immunosuppressive therapy to be aware of this serious but reversible adverse effect.

Left ventricular noncompaction cardiomyopathy.

Isolated left ventricular noncompaction (ILVNC) is a congenital abnormality in the structure of ventricular tissue due to amorphogenetic defect during embryogenesis. This rare entity can be easily diagnosed by the characteristic appearance of prominent trabeculations and deep inter-trabecular spaces. Clinical manifestations of this disease include benign and malignant ventricular arrhythmia, congestive heart failure signs, cardio-embolic events (stroke), mitral and pulmonary valve incompetence, and reduced global ventricular systolic function. We present the case report of a 58-year-old man with ILVNC.

Carotenoids and asymptomatic carotid atherosclerosis.

High plasma concentrations of lycopene and beta-carotene have been associated with reduced prevalence of cardiovascular disease. The aim of this study is to compare plasma concentrations of these carotenoids in subjects with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. One hundred and sixty-five subjects underwent physical examination and ultrasonic measurement of common carotid artery intima-media thickness. Analysis of variance and logistic regression methods were used to determine whether differences existed between participants with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. Of the 165 participants, 80 exhibited evidence of carotid atherosclerosis (carotid intima-media thickness>0.8 mm), while 85 did not (carotid intima-media thickness>0.8 mm), while 85 did not (carotid intima-media thickness<0.8 mm). Participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly greater body mass index, significantly higher serum concentrations of total cholesterol, LDL-associated cholesterol and triglycerides, and significantly higher plasma concentrations of uric acid, C-reactive protein and fibrinogen. In contrast, participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly lower plasma concentrations of lycopene and beta-carotene. These results suggest that lycopene and beta-carotene may play important roles in delaying the development of the early asymptomatic stage of carotid atherosclerosis. Encouraging adequate intakes of antioxidant carotenoids may provide an important public health service.

Relationship between asymmetric dimethylarginine and asymptomatic carotid atherosclerosis.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) associated with an increased risk of cardiovascular disease (CVD). In this study we assessed the relationship between ADMA and asymptomatic carotid intima-media thickness (CIMT). Eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). None of the subjects had symptoms of carotid atherosclerosis and nor were they taking any medication. Statistical analyses showed that high plasma levels of ADMA were positively correlated to CIMT (p less than 0.001). Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p less than 0.001). High serum concentrations of ADMA were associated with early carotid atherosclerotic lesions as measured by CIMT and represent a new marker of asymptomatic carotid atherosclerosis.

Circulating plasma antioxidants, inflammatory markers and asymptomatic carotid atherosclerosis in end-stage renal disease patients: a case control study.

Few studies have been conducted on the relationship between antioxidant plasma vitamin concentrations, inflammatory markers and carotid atherosclerosis with inconclusive results in endstage renal disease (ESRD) patients. A case-control study was performed to investigate the relationship between plasma antioxidant concentrations, inflammatory markers, and carotid intima-media thickness (CIMT) in healthy subjects and in patients undergoing hemodialysis (HD). We enrolled 40 subjects (20 healthy, 20 with ESRD) asymptomatic for carotid atherosclerosis. After carotid ultrasound investigation (CUI), medical history data, physical examination, venous blood samples were collected. These were analyzed for concentrations of antioxidant vitamins (A, E), carotenoids (lycopene, beta-carotene), inflammatory markers (C-reactive protein, fibrinogen), and lipid profile. Low concentrations of vitamin A, vitamin E, lycopene, and beta-carotene were significantly associated with carotid atherosclerosis in patients with ESRD (p less than 0.001). In addition, high concentration of low density lipoprotein cholesterol and total cholesterol (p less than 0.01), C-reactive protein and fibrinogen (p less than 0.001) were also associated with carotid atherosclerosis, while other laboratory parameters considered (high density lipoprotein cholesterol and triglycerides) were not significantly associated with carotid atherosclerosis. A regular intake of foods rich in antioxidant vitamins with low fat concentrations may slow the progression of atherosclerotic process in this group of patients.

Blood cholesterol concentration measured by CR3000: fingerstick versus venous sampling.

Currently, the clinical practice of desktop or Point of Care (PoC) analyzers for lipid measurements has gained wide popularity. Designed to quickly perform measurements on microlitre(microL) quantities of blood, these instruments can be used in non-laboratory settings, such as physicians offices or field-testing sites and can provide measurements in whole blood, serum, or plasma, using either venous or capillary blood samples. The aim of this study is to examine the relationship between cholesterol determinations in venous and capillary samples using the CR3000 PoC system. The study was performed on 21 unselected adult volunteers, and no exclusion criteria was adopted. The mean cholesterol concentration for the venous blood samples measured was 164 mg/dL. The values obtained in the capillary blood samples averaged 168 mg/dL, which is only slightly higher (e.g., 2.87%) than the venous sample measurements. Moreover, the total variance was statistically similar for venous and capillary measurements (F value = 1.199, where the upper critical value of the F distribution is 2.124, p < 0.05). The results of our study support the concept that CR3000 total cholesterol testing can be performed safely and accurately in either venous or capillary specimens.

Protective effect of lycopene in cardiovascular disease.

Coronary artery disease (CAD) represents the primary cause of death in Western Countries with an high incidence on human health and community social costs. Oxidative stress induced by reactive oxygen species (ROS) plays an important role in the aetiology of this disease. In particular, the LDL-oxidization has a key role in the pathogenesis of atherosclerosis and cardiovascular heart diseases through the initiation of plaque formation process. Dietary phytochemical products such antioxidant vitamins (A,C,E) and bioactive food components (alpha- and beta-carotene) have shown an antioxidant effect in reducing both oxidative markers stress and LDL-oxidization process. Scientifical evidences support the beneficial roles of phytochemicals in the prevention of some chronic diseases. Lycopene, an oxygenated carotenoid with great antioxidant properties, has shown both in epidemiological studies and supplementation human trials a reduction of cardiovascular risk. However, controlled clinical trials and dietary intervention studies using well-defined subjects population haven't been provided a clear evidence of lycopene in the prevention of cardiovascular diseases. The present short review aims to evaluate the beneficial effect of lycopene in the prevention of cardiovascular disease.

Reduction of intima-media thickness in subjects with asymptomatic carotid disease: two cases from the Asymptomatic Carotid Atherosclerosis DIsease Manfredonia Study (ACADIM Study).

The intima-media thickness (IMT) of carotid common arteries (CCA) represents an important step of carotid plaque formation and progression, and is a characteristic marker of atherosclerosis, one of the most principal determinants of coronary artery disease (CAD). Change in IMT is one of the currently used markers to evaluate the progression of atherosclerotic process. In particular rosuvastatin (ROS) has demonstrated in a large scale controlled study with placebo a significant reduction of coronary atherosclerosis. Two subjects with normal lipidic profile underwent a carotid ultrasound investigations (CUI) and received ROS (10 mg/day). The CUI documented a bilateral IMT of CCDX and CCSX for the case A (0.101 cm dx-0.105 cm sx; mean 0.103 cm) and B (0.114 cm dx-0.108 cm sx; mean 0.111 cm), in absence of stenosis or occlusion. After 16 treatment-weeks with ROS it has found a significant reduction of IMT for both case A (0.081 cm dx -0.096 cm sx; mean 0.088 cm) than case B (0.082 cm dx-0.084 cm sx; mean 0.083 cm). The treatment with ROS has been well tolerated and no adverse effects has been reported. ROS represents an efficacious IMT-lowering agent of the statin class. The two presented case reports confirm the benefit of ROS in the IMT reduction in subjects with normal LDL-C values.

Compliance therapy with anti-inflammatory antiasthmatic drugs: inhaled corticosteroids and leukotriene receptor antagonists.

Bronchial asthma represents the commonest chronic respiratory disease in industrialized countries and its prevalence is increasing throughout the world. This is a chronic inflammatory disease in which the inflammation constitutes an important predisposing condition for airway remodelling and secondary irreversible airflow obstruction. The current approach for the treatment involves many classes of drugs, particularly anti-inflammatory such inhaled and oral corticosteroids and cysteinyl-leukotriene receptor antagonist. The pharmacology of drugs used in asthma represents an important factor that conditioning the effectiveness of therapy. In fact, many studies have demonstrated that some asthmatic patients have particular problems that deserve special treatment. Another important factor of asthma treatment is represented by delivery devices for the inhalation of medications and their correct use because, at the present, it is estimated that compliance to controller anti-asthmatic therapy is no more than 50%. The aim of this review is to focus on the compliance in the treatment of asthma and the use of antiinflammatory therapies with inhaled corticosteroids and leukotriene receptor antagonist drugs.

Antileukotriene drugs: clinical application, effectiveness and safety.

Cysteinyl leukotrienes (Cys-LTs) are potent proinflammatory mediators derived from arachidonic acid through the 5-lypoxigenase (5-LO) pathway. They exert important pharmacological effects by interaction with at least two different receptors: Cys-LT(1) and Cys-LT(2). By competitive binding to the Cys-LT(1) receptor, leukotriene receptor antagonist drugs such as montelukast, zafirlukast, and pranlukast, block the effects of Cys-LTs and alleviate the symptoms of many chronic diseases, especially bronchial asthma and allergic rhinitis. Evidence obtained by randomized clinical trials as also by direct experience derived from patients suffering from asthma and allergic rhinitis justifies a broader role for leukotrienes receptor antagonists (LTRAs). Recently published studies and case reports have demonstrated beneficial effects of LTRAs on other diseases commonly associated with asthma (exercise induced asthma, rhinitis, chronic obstructive pulmonary disease, interstitial lung disease, chronic urticaria, atopic dermatitis, allergic fungal disease, nasal polyposis, and paranasal sinus disease) as well as other diseases not connected to asthma (migraine, respiratory syncytial virus postbronchiolitis, systemic mastocytosis, cystic fibrosis, pancreatitis, vulvovaginal candidiasis, cancer, atherosclerosis, eosinophils cystitis, otitis media, capsular contracture, and eosinophilic gastrointestinal disorders). The aim of this review is to show the most recent applications and effectiveness in clinical practice of the LTRAs.