Cardiomyopathy hypertrophic

Troponin is a regulator of striated muscle contraction. Measurements of troponin I levels are routinely used in the diagnosis of myocardial infarction. In addition, mutations in the troponin I subunit are associated with familial hypertrophic cardiomyopathy. 

Sorcin is associated with the development of multidrug resistances in leukemia and other cancels. Sorcin is also able to improve cardiac contractility independently of (3-adienergic stimulation and may prove beneficial in treatment of heart failure. A point mutation in sorcin causes familial hypertrophic cardiomyopathy. 

In a previous section we mentioned the significance of myosin filament structure. In nematodes two forms of myosin-II, myosin A and B, are required for proper filament stmcture (Epstein, 1988). The two forms of myosin are expressed at the proper time to allow for correct filament assembly. An accessory protein called paramyosin is also required for correct filament assembly. In vertebrate cardiac muscle, there are also two isoforms of myosin-II a-myosin and p-myosin. The proper ratio of these two proteins is of utmost importance for proper muscle activity. The incorrect synthesis of a- and P-myosins results in a severe cardiac disorder known as hypertrophic cardiomyopathy. Genetic transmission of the disease occurs in about 55% of families. The inherited condition is called familial hypertrophic cardiomyopathy (FHC), and this condition is a leading cause of sudden death in young athletes. 

Hypertrophic cardiomyopathy (HCM) is characterized by abnormal left ventricular thickening. The left ventricular septum is the most common site of involvement. Pathologically, the disease is characterized by myocardial fiber disarray. The myocardium may exhibit extensive scarring and disorganization of interstitial and intercellular tissue (Elstein et al., 1992). The severity of HCM depends on the age of the patient, as well as the extent of the disarray. Patients with HCM have variable... 

Geisterfer-Lowrance, A.A., Kass, S., Tanigawa, G., Vosberg, H.-P., McKenna, W., Seidman, C.E., Seidman, J.G. (1990). A molecular basis for familial hypertrophic cardiomyopathy a p-cardiac myosin heavy chain gene missense mutation. Cell 62, 999-1006,... 

Mutations in the Cardiac (i-Myosin Heavy Chain Gene Are One Cause of Familial Hypertrophic Cardiomyopathy... 

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.

Some cases of famifial hypertrophic cardiomyopathy are due to missense mutations in the gene coding for p-myosin heavy chain. 

Scriver CR et al (editors) The Metabolic and Molecular Bases of Inherited Disease, 8th ed. McGraw-Hill, 2001. (This comprehensive four-volume text contains coverage of malignant hyperthermia [Chapter 9], channelopathies [Chapter 204], hypertrophic cardiomyopathy [Chapter 213]> the muscular dystrophies [Chapter 216], and disorders of intermediate filaments and their associated proteins [Chapter 221].)... 

Ventricular hypertrophy (e.g., hypertrophic cardiomyopathy, other examples above)... 

Tachyarrhythmias -Bradyarrhythmias -Valvular heart disease (espec. AS) -Hypertrophic cardiomyopathy... 

Elderly Clinical experience for organic nitrates reported in the literature identified a potential for severe hypotension and increased sensitivity to nitrates in the elderly. Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy. 

Angina Nitrate therapy may aggravate angina caused by hypertrophic cardiomyopathy. 

Hypertrophic cardiomyopathy (IHSS) Serious adverse effects were seen in 120 patients with IHSS (especially with pulmonary artery wedge pressure more than 20 mm Hg and left ventricular outflow obstruction) who received oral verapamil at doses up to 720 mg/day. Sinus bradycardia occurred in 11%, second-degree AV block in 4% and sinus arrest in 2%. 

Verapamil and a few newer dmgs of this category are vasodilator agents, which in addition impair AV conduction, reduce heart rate and cardiac contractile force. Verapamil was initially developed for the treatment of supraventricular tachycardia and it continues to be an important drug for the management of this condition, also postoperatively. Verapamil is the CA of choice in the management of hypertrophic cardiomyopathy. Verapamil is also used in the treatment of stable angina and, less frequently, essential hypertension. 

Effective in mitral valve prolapse, hypertrophic cardiomyopathy, digitalis-related ectopic activity, and ventricular complexes associated with exercise or induced by ischemia. 

In heart diseases like hypertension, heart failure, ischemia, and hypertrophic cardiomyopathy (HCM) as well as dilated cardiomyopathies (DCM), total myocardial jS-AR density is reduced [90-94], A selective reduction of p -ARs without change of P2-AR density is often observed in the failing human heart [89], Therefore, there is a clinical need for the noninvasive assessment of p-AR density in vivo. PET is capable of assessing receptor concentrations in vivo, provided that a radioligand radiolabeled with a positron emitter specifically and selectively binds to the target receptor, and metabolism of the radiotracer does not occur in target tissue. 

S.T. LI, C.J. Tack, L. Fananapazir, D.S. Goldstein, Myocardial perfusion and sympathetic Innervation In patients with hypertrophic cardiomyopathy, J. Am. Coll. Cardiol. 35 (2000) 1867-1873. 

H. Tuunanen, J. Kuusisto, J. Toikka, P. Jaaskelainen, P. Maijamaki, K. Peuhkurinen, T. Viljanen, P. Sipola, K.Q. Stolen, J. Hannukainen, P. Nuutila, M. Laakso, J. Knuuti, Myocardial perfusion, oxidative metabolism, and free fatty acid uptake in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene A positron emission tomography study, J. Nucl. Cardiol. 14(2007) 354-365. 

Unlabeled Uses Treatment of anxiety, chronic angina pectoris, hypertrophic cardiomyopathy, MI, pheochromocytoma, syndrome of mifral valve prolapse, thyrotoxicosis, tremors... 

Unlabeled Uses Acute alcohol withdrawal, arrhythmia (especially supraventricular and ventricular tachycardia), improved survival in diabetics with heart disease, mild to moderately severe CHF (adjunct) prevention of migraine, thyrotoxicosis, tremors treatment of hypertrophic cardiomyopathy, pheochromocytoma, and syndrome of mitral valve prolapse... 

Unlabeled Uses Treatment of arrhythmias, hypertrophic cardiomyopathy. Ml, mitral valve prolapse syndrome, neuroleptic-induced akathisia, pheochromocytoma, tremors, thyrotoxicosis, vascular headaches... 

Uniabeled Uses Treatment of chronic angina pectoris, hypertrophic cardiomyopathy, tremors, and mitral valve prolapse syndrome. Increases antidepressant effect with fluoxetine and other SSRIs. 

Unlabeled Uses Systemic-. Treatment of anxiefy, cardiac arrhyfhmias, chronic angina pecforis, hypertrophic cardiomyopathy, migraine, pheochromocytoma, thyrotoxicosis, tremors... 

G. N. Shivu, K. Abozguia, T. T. Phan, 1. Ahmed, A. Herming and M. Frenneaux, P magnetic resonance spectroscopy to measure in vivo cardiac energetics in normal myocardium and hypertrophic cardiomyopathy experiences at 3 T. Eur. J. Radiol, 2010, 73, 255-259. 

In addition to angina, calcium channel blockers have well-documented efficacy in hypertension (see Chapter 11) and supraventricular tachyarrhythmias (see Chapter 14). They also show moderate efficacy in a variety of other conditions, including hypertrophic cardiomyopathy, migraine, and Raynaud s phenomenon. Nifedipine has some efficacy in preterm labor but is more toxic and not as effective as atosiban, an investigational oxytocin antagonist (see Chapter 17). 

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