Dilating cardiomyopathies

Dystrophin Attached to plasma-lemma Deficient in Duchenne muscular dystrophy. Mutations of its gene can also cause dilated cardiomyopathy. 

Another type of cardiomyopathy is termed dilated cardiomyopathy. Mutations in the genes encoding dystrophin, muscle LIM protein (so called because it was found to contain a cysteine-tich domain originally detected in three proteins Lin-II, Isl-1, and Mec-3), and the cyclic response-element binding ptotein (CREB) have been implicated in the causation of this condition. The first two proteins help organize the conttactile ap-params of cardiac muscle cells, and CREB is involved... 

Figure 49-13. Simplified scheme of the causation of familial hypertrophic cardiomyopathy (MIM 192600) due to mutations in the gene encoding fi-myosin heavy chain. Mutations in genes encoding other proteins, such as the troponins, tropomyosin, and cardiac myosin-binding protein C can also cause this condition. Mutations in genes encoding yet other proteins (eg, dystrophin) are involved in the causation of dilated cardiomyopathy.

O The most common causes of heart failure are coronary artery disease (CAD), hypertension, and dilated cardiomyopathy. 

Weekes J et al. Bovine dilated cardiomyopathy proteomic analysis of an animal model of human dilated cardiomyopathy Electrophoresis 1999 20 898-906. Doherty NS et al. Analysis of changes in acute phase plasma proteins in an acute inflammatory response and in rheumatoid arthritis using two-dimensional gel electrophoresis. Electrophoresis 1998 19 355-363. 

Polymorphisms of the beta adrenergic receptors have also been studied in patients with heart failure and cardiomyopathy, or other complex and rather ill-defined phenotypes. In patients with heart failure due to ischemic or idiopathic dilated cardiomyopathy, the Thrl64Ile polymorphism in the />2-adrerioreceplor was significantly associated with survival rate at one year [62]. Similarly, the Ser49Gly polymorphism of the /Vadrenoreceptor gene has been linked to the improved survival of patients with idiopathic cardiomyopathy [63]. However, sample size was limited in those studies and results need to be confirmed in adequately powered studies. 

Ventricular tachycardia (VT) is defined by three or more repetitive PVCs occurring at a rate greater than 100 beats/min. It occurs most commonly in acute myocardial infarction (MI) other causes are severe electrolyte abnormalities (e.g., hypokalemia), hypoxemia, and digitalis toxicity. The chronic recurrent form is almost always associated with underlying organic heart disease (e.g., idiopathic dilated cardiomyopathy or remote MI with left ventricular [LV] aneurysm). 

Causes of systolic dysfunction (decreased contractility) are reduction in muscle mass (e.g., myocardial infarction [MI]), dilated cardiomyopathies, and ventricular hypertrophy. Ventricular hypertrophy can be caused by pressure overload (e.g., systemic or pulmonary hypertension, aortic or pulmonic valve stenosis) or volume overload (e.g., valvular regurgitation, shunts, high-output states). 

Animal models have established that infections can induce autoimmune disease. For example, coxsackievirus B3 infection of susceptible strains of mice results in inflammation in the heart that resembles the myocarditis and dilated cardiomyopathy that occurs in humans.28 44 The same disease can be induced by injecting mice with cardiac myosin mixed with adjuvant, thereby reproducing the disease in the absence of virus infection, indicating that an active viral infection is not necessary for the development of autoimmune disease.9 29 44 Likewise, a number of autoimmune diseases can be... 

Encyclopedia Dilated Cardiomyopathy httpv/www.nlm.nih.gov/medlineplus/ency/article/000168.htm... 

Dilated cardiomyopathy Heart muscle disease that leads to enlargement of the heart s chambers, robbing the heart of its pumping ability. [NIH]... 

Herrmann, S., Schmidt-Petersen, K., Pfeifer, J., et al. (2001) A polymorphism in the endothe-lin-A receptor gene predicts survival in patients with idiopathic dilated cardiomyopathy. Eur. Heart]. 22, 1948-1953. 

Telgmann, R., Harb, B. A., Ozcelik, C., et al. (2007) The G-231A polymorphism in the endothelin-A receptor gene is associated with lower aortic pressure in patients with dilated cardiomyopathy. Am. J. Hypertens. 20, 32-37. 

Charron, P., Tesson, E., Poirier, O., et al. (1999) Identification of a genetic risk factor for idiopathic dilated cardiomyopathy. Involvement of a polymorphism in the endothehn receptor type A gene. CARDIGENE group. Eur. Heart J. 20, 1587-1591. 

On the other hand, clinical evidence suggests that p-blockers produce favorable effects in certain forms of congestive heart failure (idiopathic dilated cardiomyopathy). 

In more recent times p-blocker on a long term were found to improve cardiac performance — particularly in idiopathic dilating cardiomyopathy — probably by preventing sympathetic overdrive. 

Merlet P, Benvenuti C, Moyse D, Pouillart F, Dubois-Rande JL, Duval AM et al. Prognostic value of MIBG imaging in idiopathic dilated cardiomyopathy. J Nucl Med 1999 40 917-923... 

Suwa M, Otake Y, Moriguchi A, Ito T, Hirota Y, Kawamura K et al. Iodine-123 metaiodobenzylguani-dine myocardial scintigraphy for prediction of response to beta-blocker therapy in patients with dilated cardiomyopathy. Am Heart J 1997 133 353-358... 

Gerson MC, Craft LL, McGuire N, Suresh DP, Abraham WT, Wagoner LE. Carvedilol improves left ventricular function in heart failure patients with idiopathic dilated cardiomyopathy and a wide range of sympathetic nervous system function as measured by iodine 123 metaiodoben-zylguanidine. J Nucl Cardiol 2002 9 608-615... 

Kadish A, Dyer A, Daubert JP, et al., for the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004 350 2151-2158. 

Conduction system abnormalities are common in chronic heart failure, occurring in 15-30% of the population with low left ventricular ejection fraction (LVEF) [1-3]. The prevalence in ischemic heart disease is roughly similar to that seen in other forms of dilated cardiomyopathy. Conduction system disease can occur both at the time of an acute myocardial infarction as well as slowly progressing in chronic ischemic heart disease. Intraventricular conduction delays are associated with a poor prognosis in heart failure, with up to a 70% increase in the risk of death, and are also more prevalent in patients with advanced symptoms [2,4]. In ischemic heart disease, all components of the conduction system are at risk of ischemic injury, from the sinoatrial node to the His-Pukinje system. These conduction system abnormalities have the potential to impair cardiac function by a number of mechanisms. Since conduction abnormalities impair cardiac function, it is logical that pacing therapies to correct or improve these conduction abnormalities may improve cardiac function. 

Atrial fibrillation is commonly associated with heart failure, and the prevalence of atrial fibrillation is related to the severity of heart failure, with less than 5% affected with very mild heart failure to nearly 50% affected with advanced heart failure [66]. Heart failure and atrial fibrillation are both common cardiovascular disorders and share the same demographic risk factors, including age, history of hypertension, prior myocardial infarction, and valvular heart disease [67, 68]. Further, the incidence of heart failure increases dramatically after the diagnosis of atrial fibrillation [69]. Progression of LV dysfunction can clearly be associated with rapid ventricular rates [70-76]. Conversely, conversion to normal sinus rhythm or control of ventricular response in atrial fibrillation can improve LV function [71-74, 77]. Accordingly, rate control becomes very important in patients with heart failure and dilated cardiomyopathy, and likely even more so when ischemia from rapid rates complicate the patient s course. 

Secondary mitral regurgitation can be a consequence of intraventricular conduction delay. Secondary mitral regurgitation is a common accompaniment of dilated cardiomyopathy of ischemic etiology. Intraventricular conduction delays can create or exacerbate mitral regurgitation by causing a lack of coordination of the papillary muscles [95]. The geometry of the mitral papillary muscles places one near... 

A series of pilot studies began with multisite pacing for patients with heart failure and dilated cardiomyopathy in the early 1990s [52, 105-111]. An improvement in LV function and symptoms of heart failure were demonstrated. This provided the interest in biventricular pacing for heart failure. The term cardiac resynchronization therapy was coined to refer to pacing therapies that attempt to enhance cardiac performance by using pacing to correct electrical conduction abnormalities in the heart. The most common form of this therapy is atrial-synchronous... 

Xiao HB, Roy C, Fujimoto S, Gibson DG. Natural history of abnormal conduction and its relation to prognosis in patients with dilated cardiomyopathy. Int. J. Cardiol. 1996 53 163-70. 

Agarwal AK, Venugopalan P. Beneficial effect of carvedilol on heart rate response to exercise in digitalised patients with heart failure in atrial fibrillation due to idiopathic dilated cardiomyopathy. Eur. J. Heart Fail. 2001 3 437-40. 

Hochleitner M, Hortnagl H, Ng CK, Gschnitzer F, Zechmann W. Usefulness of physiologic dual-chamber pacing in drug-resistant idiopathic dilated cardiomyopathy. [see comment]. Am. J. Cardiol. 1990 66 198-202. 

Gold MR, Shorofsky SR, Metcalf MD, Feliciano Z, Fisher ML, Gottlieb SS. The acute hemodynamic effects of right ventricular septal pacing in patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am. J. Cardiol. 1997 79 679-81. 

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