Current Pharmaceutical Design - Volume 16, Issue 26, 2010

In the last decade there has been made much progress in defining clinical diagnosis and therapy of cardiomyopathies. Initially, some new types of cardiomyopathies, such as Takotsubo and Non Compaction of the Myocardium Ventricle were better defined, which were then incorporated fully in the guidelines and classification tables. Alongside technological development new diagnostic approaches, have been suggested and thus techniques such as nuclear magnetic resonance to high resolution and three-dimensional CARTO mapping endoventricular are part of the routine diagnostic of Arrhythmogenic right ventricular cardiomyopathy. Three-dimensional echocardiography is suggested as a possible additional tool in the diagnosis of Non Compaction, Delay Enhancement as a parameter able to define the degree of risk of hypertrophic or dilated cardiomyopathy; CT coronary as relevant inquiry in patients with hypertrophic cardiomyopathy to search intramyocardial bridges, and much more. This issue fits into the view, strongly evolution and seeks to analyze these diagnostic therapeutic advances. First, the Tigen et al. have addressed the age-old theme of beta blocker treatment in dilated cardiomyopathy, trying to answer the question “What's the best of all?” [1]. Malato et al. have instead analyzed the forms of dilated cardiomyopathy as a result of a haematological disease presenting the possibility of treatment [2]. In their review the group of Vienna addressed the problem of arrhythmias in noncompaction ventricular myocardium and the problem of treatment of co-morbidity neurological disorders in these patients [3,4]. Palecek et al. and Kida et al. instead have gutted two revisions challenging the long standing issue of treatment in acute and chronic Takotsubo therapy [5, 6]. Corrado et al. have attempted to define the best diagnostic and therapy in arrhythmogenic right ventricular cardiomyopathy in light of current knowledge and their experience [7]. Last work by Mongiovi et al. analyzed aspects of cardiomyopathies in the fetal period, where the diagnosis is complex and treatment almost impossible [8]. In general, this issue is an interesting support for those involved in the diagnosis and treatment of these diseases, and a major upgrade in terms of cardiomyopathies.....

Among the multiple pharmacologic and non-pharmacologic therapies, beta-blockers seem to be the mainstay of heart failure management. Although the first large studies failed to demonstrate a significant improvement in mortality, the results from subsequent studies revealed significant risk reductions in mortality with metoprolol, carvedilol and bisoprolol. Decision of the appropriate therapeutic agent depends on the existence of some specific conditions complicating dilated cardiomyopathy. This article reviews the impact of beta-blocker therapy in patients with dilated cardiomyopathy of ischemic or non-ischemic etiology.

Several publications have focused on the cardiotoxicity of specific classes of haematological therapeutic agents such as antracyclines and cyclofosfamide. Cardiotoxicity of cancer chemotherapeutics is a problem for patients of all ages, but it increases with age. Toxicity can also be developed months after the last chemotherapy dose, and late reactions can be seen years later when they present new-onset cardiomyopathy. No data are available about the cardiotoxicity of non-chemotherapy agents currently used as preferred therapy for haematological malignancy in elderly. In this review we have provided a summary of the cardiovascular toxic effects produced by different drugs and therapeutic agents. Early identification of patients who are at risk for cardiotoxicity should be a primary goal for haematologists in the development of personalised antineoplastic therapeutic strategies or interventions. Thus, the discovery of new biomarkers to identify patients at a high risk for the development of these complications is a high priority. Although targeted therapies such as imatinib and anti-CD20 antibody, such as rituximab, are considered less toxic and better tolerated by patients compared with classic chemotherapy drugs, certain cardiological complications can be very serious as these agents have been in use for a limited period of time.

Arrhythmias in left ventricular hypertrabeculation/noncompaction (LVHT) comprise sustained or non-sustained ventricular tachycardia (VT) (n=135), atrial fibrillation (AF) (n=96) AV block (n=55) and QT prolongation (n=47). The prevalence differs between children and adults. In children most frequent are WPW-syndrome (n=24), AV block (n=24), VT (n=17) and bradycardia (n=15). In adults most frequent arrhythmias are VT (n=118), AF (n=95), QT prolongation (n=42) and AV block (n=31). Some arrhythmias are more frequently reported in children than in adults like WPW-syndrome (24 vs. 17 patients), second-degree AV block (4 vs. 0 patients), bradycardia (15 vs. 3 patients) and ventricular fibrillation (VF) (9 vs. 5 patients). There are nearly no pediatric cases with AF (1 vs. 95 patients). In 120 patients implantable cardioverters/defibrillators have been implanted for primary or secondary prevention of sudden cardiac death. The pathomechanisms of arrhythmias in LVHT are largely unknown, especially if patients with LVHT and neuromuscular disorders are more prone to arrhythmias than patients without. There is a need to clarify risk factors for VT or VF because 19% of LVHT patients with VT or VF have a normal systolic function and demonstration of systolic dysfunction is no reliable risk marker. Data about long-term follow- up of LVHT patients with implanted cardioverters/defibrillators are necessary since the indication for prophylactic implantation is still unclear. AF in LVHT increases the embolic risk, thus it would be useful to know which LVHT patients who have sinusrhythm at baseline are prone to develop AF in order to start early with anticoagulant therapy.

Left ventricular hypertrabeculation / noncompaction (LVHT) is in the majority of the cases associated with hereditary cardiac or skeletal muscle disease or with chromosomal abnormalities. Depending on the study more than two thirds of the LVHT patients also present with a neuromuscular disorder (NMD). NMDs most frequently associated with LVHT are the Barth syndrome, mitochondrial disorders, zaspopathy, and myotonic dystrophies. NMDs only occasionally presenting with LVHT are the dystrobrevinopathy, laminopathies, dystrophinopathies, myoadenylat-deaminase deficiency, hereditary inclusion body myositis and the hereditary neuropathy CMT1A. A causal relation between NMDs and LVHT is likely, although the exact relationship and pathomechanic association remains elusive. The close pathogenetic relation is supported by the fact that the phenomenon of acquired LVHT occurs predominantly in NMDs. Consequent referral of LVHT patients to the neurologist, consequent referral of NMD patients to the cardiologist, and family investigations may help to elucidate unsolved issues concerning the pathogenesis, course and prognosis of LVHT.

Takotsubo cardiomyopathy (TC) is a condition most prevalent in postmenopausal women, characterized by transient left ventricular dysfunction following acute emotional or physical stress. Direct catecholamine-mediated myocyte injury and microvascular dysfunction leading to myocardial stunning are believed to play a major role in its pathogenesis. The treatment of TC remains empirical. In the acute phase, therapy must be individualized depending on hemodynamic situation. In stable conditions, it appears advantageous to prevent excessive sympathetic activation by combining alpha and beta blockade. Beta blockers are used to treat dynamic left ventricular obstruction. Phenylephrine may represent an alternative approach in patients presenting with outflow tract obstruction and severe hypotension. In hemodynamically unstable patients, early administration of intra-aortic balloon pump counterpulsation should be considered. As no consensus currently exists with respect to the chronic management of TC, randomized clinical trials are urgently needed with focus on treatment strategies.

Takotsubo cardiomyopathy was first reported in Japan in 1990. Recently, an increasing number of case reports and reviews of takotsubo cardiomyopathy has been published worldwide, including atypical cases with inverted takotsubo cardiomyopathy or incidental coronary artery disease. To date, there has been no guideline for worldwide consensus on takotsubo cardiomyopathy diagnostic criteria and treatment. The onset mechanism of takotsubo cardiomyopathy is still controversial, although, catecholamine cardiotoxicity is considered to be the most likely cause. Here, we summarize the current case reports and reviews in regard to diagnosis, cardiac biomarkers, electrocardiogram, cardiac imaging, mechanism, treatment and prognosis in order to establish a deeper understanding of this syndrome.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic heart muscle disease characterized by the peculiar right ventricular (RV) involvement. Distinctive pathologic features are myocardial atrophy and fibro-fatty replacement of the RV free wall, and clinical presentation is usually related to ventricular tachycardias with a left bundle branch block pattern or ventricular fibrillation leading to cardiac arrest, mostly in young people and athletes. Later in the disease evolution, progression and estension of RV muscle disease and left ventricular involvement may result in right or biventricular heart failure. In 1994 an International Task Force proposed standardized diagnostic criteria designed to guarantee an adequate specificity based on the presence of major and minor criteria encompassing electrocardiographic, arrhythmic, morphofunctional, histopathologic, and genetic factors; more recently, Task Force criteria have been modified to increase their diagnostic sensitivity. Retrospective analysis of clinical and pathologic series including fatal cases identified a series of risk factors such as malignant familial background, youthful age, previous syncope or cardiac arrest, competitive sport activity, severe RV disease with left ventricular involvement, and episodes of complex ventricular arrhythmias or ventricular tachycardia. The therapeutic options include beta blockers, antiarrhythmic drugs, catheter ablation, and implantable cardioverter defibrillator (ICD). The ICD is the most effective safe-guard against arrhythmic sudden death. In patients in whom ARVC has progressed to severe RV or biventricular systolic dysfunction with risk of thromboembolic complications, treatment consists of current therapy for heart failure including anticoagulant therapy. In case of refractory congestive heart failure, patients may become candidates for heart transplantation.

Cardiomyopathies (CM) are a very rare disease in fetuses with a very poor outcome. Only isolated case reports and small case series have been reported. According to the published studies we will describe the fetal CM starting from their echocardiographic presentation: dilated cardiomyopathy (DCM) with dilatation of either or both ventricles and impaired ventricular function, and hypertrophic cardiomyopathy (HCM) with different degrees of disproportionate hypertrophy of the myocardial walls. The term of “noncompaction” of the left ventricular myocardium, is used in cases with DCM with evidence of numerous prominent trabeculations with deep myocardial recesses. In a series of neonates and infants, the CM occur in about 2-7%, but probably during the fetal life the prevalence is higher: 6% - 11%. The high intrauterine loss, occurring in one-third of the affected fetuses, likely accounts for these differences. Fetal echocardiography, B and M-mode, is the main diagnostic tool and it is useful for therapeutic orientation and to determine the neonatal outcome. A hemodynamic evaluation can be performed by Doppler mode. Systolic and diastolic fetal cardiac functions have become part of the routine evaluation of the fetal heart. Cardiomyopathies can be isolated or associated with other cardiac and non-cardiac malformations. All the studies confirm a great variability of DCM in the fetal age as for the anatomical and functional forms, etiology and hemodynamic impact with different final outcomes. Genetic, metabolic, infective, and cardiac diseases may present with DCM. Ventricular dysfunction may be progressive in utero and after birth, but possibility of improvement or even normalization of the left ventricular dysfunction is known in all forms of DCM, “idiopathic”, post infective or in noncompaction of left ventricle. The outcome is worse in the presence of fetal hydrops, significant atrioventricular valve regurgitation, for the earlier age at presentation and when diastolic dysfunction is associated with systolic dysfunction. Etiologically primary fetal HCM is a heterogeneous condition that can be the result of intrinsic fetal pathology as well as of extrinsic factors. It can be concentric or asymmetric. Prognosis of infants with HCM associated with maternal diabetes is good, while a bad prognosis has been reported in fetuses without diabetic mother. HCM may be evolutive, mainly after birth; otherwise, there are also cases that improve or regress completely. Unfortunately, a poor outcome is observed, particularly in DCM, with only a few therapeutic options available. Detailed evaluation of fetal and maternal condition provides prognostic information for prenatal counselling and may lead to improved outcome of at least some affected pregnancies.

Objective: This review focuses on the efficacy and safety of effective herbal medicines in the management of hyperlipidemia in human. Methods: PubMed, Scopus, Google Scholar, Web of Science, and IranMedex databases were searched up to 11th May 2010. The search terms were “hyperlipidemia” and (“herbal medicine” or “medicine traditional”, “extract plant”) without narrowing or limiting search elements. All of the human studies on the effects of herbs with the key outcome of change in lipid profiles were included. Results: Fifty three relevant clinical trials were reviewed for efficacy of plants. This study showed significant decrease in total cholesterol and LDL cholesterol after treatment with Daming capsule (DMC), chunghyul-dan, Glycyrrhiza glabra, garlic powder (Allicor), black tea, green tea, soy drink enriched with plant sterols, licorice, Satureja khuzestanica, Monascus purpureus Went rice, Fenugreek, Commiphora mukul (guggul), Achillea wilhelmsii C. Koch, Ningzhi capsule (NZC), cherry, compositie salviae dropping pill (CSDP), shanzha xiaozhi capsule, Ba-wei-wan (hachimijiogan), rhubarb stalk, Silybum marianum, Rheum Ribes and Jingmingdan granule (primrose oil). Conflicting data exist for red yeast rice, garlic and guggul. No significant adverse effect or mortality were observed except in studies with DMC, guggul, and Terminalia belerica, Terminalia chebula, Emblica officinalis, ginger, and garlic powder (Allium sativum). Conclusion: Amongst reviewed studies, 22 natural products were found effective in the treatment of hyperlipidemia that deserve further works to isolate and characterization of their constituents to reach novel therapeutic and more effective agents.