Different Forms Of Cardiomyopathies Research Articles

Detection of apical hypertrophic cardiomyopathy; which is the appropriate imaging modality

Apical hypertrophic cardiomyopathy is a form of hypertrophic cardiomyopathy localized to the left ventricular apex. The disease is common in Japanese and other Asian populations but its presence has also been recognized, though less commonly, in non-Asian patients. Its prognosis is relatively benign in terms of cardiovascular mortality but morbid sequelae, such as diastolic dysfunction, left atrial enlargement, apical thrombi, ventricular aneurysms, and myocardial infarction, may occur. In patients with apical hypertrophic cardiomyopathy, the electrocardiographic changes and symptoms associated often mimic acute coronary syndromes. Invasive or noninvasive evaluation of the left ventricular cavity confirms the diagnosis of apical hypertrophic cardiomyopathy, with the “ace-of-spades” sign on left ventriculography being pathognomonic. It is therefore of utmost importance to use the appropriate imaging modalities to establish the correct diagnosis of apical hypertrophic cardiomyopathy. For instance, using doppler-echocardiography in 182 patients with apical hypertrophic cardiomyopathy, three morphologically distinct phenotypes i.e. (1) pure focal, (2) pure diffuse, and (3) a mixed type according to patterns of hypertrophy could be discerned [1]. Detailed subtyping turned out to be important in the prediction of development of atrial fibrillation, left atrial volume index and left ventricular longitudinal function. In the current edition of this issue, Duygu et al. [2] studied 17 patients with chest pain who had a pre-diagnosis of coronary artery disease but a final diagnosis of apical hypertrophic cardiomyopathy. Interestingly, all patients showed typical spade-like appearance of the left ventricle by contrast ventriculography and giant negative T-waves on the electrocardiogram. Transthoracic echocardiography showed a maximum wall thickness of 18 ± 4 mm and a mean gradient of 30 mmHg by Doppler echocardiography. None of the patients showed significant coronary artery disease; four patients showed myocardial bridging. The authors recommended that the diagnosis of apical hypertrophic cardiomyopathy should always be considered in certain patients with typical anginal symptoms and outspoken negative T waves on the electrocardiogram. As a result, physicians caring for patients with chest pain should consider apical hypertrophic cardiomyopathy in their differential diagnosis in case of a patient with chest pain and electrocardiographic changes suggestive of coronary artery disease. Stated by the authors, these patients should all undergo echocardiography to separate apical hypertrophic cardiomyopathy from acute myocardial ischemia. Although the authors mention that ischemic evaluation was not performed, they only refer to thallium myocardial scintigraphy as potential modality to identify ischemia in apical hypertrophic cardiomyopathy. Indeed, myocardial scintigraphy using perfusion tracers and metabolic markers have shown to be useful in the evaluation of cardiomyopathies [3–6]. It is, however, noteworthy that the authors did not refer to cardiac magnetic resonance imaging (CMR) as an accurate and reliable means of evaluating cardiac morphology, ventricular function, and myocardial perfusion, both for the left and the right ventricle therewith covering a whole spectrum of cardiac diseases [7–12]. In particular, CMR is very well suited for identifying and characterizing patients with hypertrophic cardiomyopathy [13, 14]. For instance, Tsukamoto et al. [15] showed systolic outward motion of the left ventricular apical wall in patients with apical hypertrophic cardiomyopathy using CMR tagging. In addition, CMR allows accurate evaluation of myocardial ischemia and infarction with the potential to establish the transmural extent of myocardial infarction with high spatial resolution [16–18]. Late gadolinium-enhanced CMR can clearly delineate subendocardial infarction and CMR appears to be more sensitive than other imaging methods in detecting small infarcts and ischemia [19–21]. In recent years, late gadolinium enhancement CMR has also been used to visualize myocardial interstitial abnormalities in patients with different forms of cardiomyopathies [22, 23]. In patients with apical hypertrophic cardiomyopathy, first-pass gadolinium delayed-enhanced CMR may show local delayed enhancement in the subendocardium in the hypertrophic lesion. The presence of perfusion defect and delayed enhancement may be a marker of a high-risk patient with apical hypertrophic cardiomyopathy [24]. On the other hand, patients with apical hypertrophic cardiomyopathy may show focal hyperenhancement of the non-hypertrophic basal lateral segment of the left ventricle, and absence of hyperenhancement of the hypertrophied apical segments [25]. It can be concluded that apical hypertrophic cardiomyopathy is a disease that may mimic coronary artery disease in a certain subset of patients. Hence, adequate diagnostic methods are needed to distinguish between these two entities. Although echocardiography remains the first line of investigation in these patients the final answer might be given by CMR.

Late contrast enhancement by CMR: more than scar?

Late contrast enhancement by CMR: more than scar?

Anthracycline-Induced Cardiomyopathy

Anthracyclines are potent chemotherapeutic agents associated with 3 different forms of cardiomyopathy. Acute cardiomyopathy is seen within 3 months of drug exposure and may take the form of either a reversible myocarditis and pericarditis or an early-onset type and a late-onset type of chronic cardiomyopathy. Chronic anthracycline-induced cardiomyopathy is treated similarly to ischemic cardiomyopathies with beta-blockade and angiotensin-converting enzyme (ACE) inhibition. This review focuses on recent research regarding mechanisms of anthracycline-induced myocardial damage, the noninvasive imaging diagnosis of anthracycline-induced cardiomyopathy, and potential areas of future research regarding genetic screening and selecting individuals at increased risk, with consideration of prophylactic treatment with medications, specifically Carvedilol and ACE inhibitors.

Z-line proteins: implications for additional functions

Z-line proteins have important structural functions. However, recent publications point to additional, previously unexpected functions and a new view is now emerging, whereby these proteins are involved in important intra- and inter-cellular signaling pathways. Their translocation to the nucleus, the interaction with other signaling molecules and the ability to facilitate macromolecular protein complexes indicate the multi-functionality of Z-line proteins. A better understanding of these emerging physiological roles of Z-line proteins might be achieved by precise investigations of specific mutations in specific domains in a subset of these proteins. Clues will be given to explain the clinical variations in the development and severity of different forms of cardiomyopathies, which are also affected by genetic redundancy and ethnic background of different patient populations.

Natriuretic peptides in relation to the cardiac innervation and conduction system.

During the past two decades, the heart has been known to undergo endocrine action, harbouring peptides with hormonal activities. These, termed "atrial natriuretic peptide (ANP)," "brain natriuretic peptide (BNP)," and "C-type natriuretic peptide (CNP)," are polypeptides mainly produced in the cardiac myocardium, where they are released into the circulation, producing profound hypotensive effects due to their diuretic, natriuretic, and vascular dilatory properties. It is, furthermore, well established that cardiac disorders such as congestive heart failure and different forms of cardiomyopathy are combined with increased expression of ANP and BNP, leading to elevated levels of these peptides in the plasma. Besides the occurrence of natriuretic peptides (NPs) in the ordinary myocardium, the presence of ANP in the cardiac conduction system has been described. There is also evidence of ANP gene expression in nervous tissue such as the nodose ganglion and the superior cervical ganglion of the rat, ganglia known to be involved in the neuronal regulation of the heart. Furthermore, in the mammalian heart, ANP appears to affect the cardiac autonomic nervous system by sympathoinhibitory and vagoexcitatory actions. This article provides an overview of the relationship between the cardiac conduction system, the cardiac innervation and NPs in the mammalian heart and provides data for the concept that ANP is also involved in neuronal cardiac regulation.

From the Sarcomere to the Nucleus: Role of Genetics and Signaling in Structural Heart Disease

The identification of genetic mutations underlying familial structural heart disease has provided exciting new insights into how alterations in structural components of the cardiomyocyte lead to different forms of cardiomyopathy. Specifically, mutations in components of the sarcomere are frequently associated with hypertrophic cardiomyopathy, whereas mutations in cytoskeletal proteins lead to dilated cardiomyopathy. In addition, extrinsic stresses such as hypertension and valvular disease can produce myocardial remodeling that is very similar to that observed in genetic cardiomyopathy. For myocardial remodeling to occur, changes in gene expression must occur; therefore, changes in contractile function or wall stress must be communicated to the nucleus via signal transduction pathways. The identity of these signaling pathways has become a key question in molecular biology. Numerous signaling molecules have been implicated in the development of hypertrophy and failure, including the beta-adrenergic receptor, G alpha(q) and downstream effectors, mitogen-activated protein kinase pathways, and the Ca(2+)-regulated phosphatase, calcineurin. In the past it has been difficult to discern which signaling molecules actually contributed to disease progression in vivo; however, the development of numerous transgenic and knockout mouse models of cardiomyopathy is now allowing the direct testing of stimulatory and inhibitory molecules in the mouse heart. From this work it has been possible to identify signaling molecules and pathways that are required for different aspects of disease progression in vivo. In particular, a number of signaling pathways have now been identified that may be key regulators of changes in myocardial structure and function in response to mutations in structural components of the cardiomyocyte. Myocardial structure and signal transduction are now merging into a common field of research that will lead to a more complete understanding of the molecular mechanisms that underly heart disease.

Critical analysis of endomyocardial biopsies from patients suspected of having cardiomyopathy. I: Morphological and morphometric aspects.

Three hundred and sixty-one biopsies obtained by bioptome from 201 patients with suspected cardiomyopathy were analysed morphologically, semiquantitatively, quantitatively, and statistically to ascertain whether or not histological examination provided a measurable pattern characterising the different forms of cardiomyopathy. In addition, we have tried to find out whether or not morphometry increases the diagnostic reliability. Heart from 29 cases (10 female and 19 male) who died as a result of road traffic accidents or other extracardiac causes were sampled, selecting specimens from sites usually biopsied during life. Of these biopsies, 16.1 per cent were of such poor quality that morphological categorisation was not possible. The mean size of biopsies was 0.79 mm2, and on average 1.38 mm2 of tissue was available per patient. The histological descriptions were grouped in eight entities; morphometric analysis of the endocardium, myocardium, and interstitium resulted in a more accurate evaluation of the morphological changes. Muscle fibre diameter showed distinct variance between several morphological groups, particularly between normal and pathological groupings and between right and left sided ventricular samples. The applied scoring system included the histological HOCM index (hypertrophic cardiomyopathy) which separated clearly this type of cardiomyopathy from other disorders. Small foci of chronic inflammatory cells were seen in 25 per cent of the biopsies and did not indicate myocarditis. This study did not confirm the possible existence of small vessel disease. Morphometric data permitted distinction between several histological groups but this did not apply to individual patients in veiw of a considerable degree of overlap of the pathological changes. Combining the various morphological features and applying measurements failed to establish a definite pattern for congestive cardiomyopathy (COCM), and alcoholic heart muscle disease could not be separated from COCM. It is, however, suggested that semiquantitative and morphometric methods are mandatory, not only to define more accurately the morphological changes, but also to provide the basis for additional biochemical, immunological, and virological analysis.