Cardiomyopathy pathophysiology

Pathophysiology can influence muscarinic activity in other ways as well. Circulating autoantibodies against the second extracellular loop of cardiac M2 muscarinic receptors have been detected in some patients with idiopathic dilated cardiomyopathy and those afflicted with Chagas1 disease caused by the protozoan Trypanosoma cruzi. These antibodies exert parasympathomimetic actions on the heart that are prevented by atropine. In animals immunized with a peptide from the second extracellular loop of the M2 receptor, the antibody is an allosteric modulator of the receptor. Although their role in the pathology of heart failure is unknown, these antibodies should provide clues to the molecular basis of receptor activation because their site of action differs from the orthosteric site where acetylcholine binds (see Chapter 2). 

Approximately 25% of all patients with hypertrophic cardiomyopathy (HCM) have latent left ventricular outflow obstruction with an intraventricular gradient (I). Pathophysiologic features are asymmetric hypertrophy of the septum and a systolic anterior movement of the anterior leaflet. Medical treatment includes betablockers, and calcium antagonists of the verapamil type. Approximately 5— 10% of the patients with outflow obstruction are refractory to such negative inotropic therapy (2). Positive inotropic drugs such as digitalis or sympathomimetics are strictly contraindicated. In the presence of atrial fibrillation, anticoagulation therapy should be started. Since endocarditis is more common in patients with HCM because of turbulence in the left ventricle, prophylactic antibiotics should be administered for periods of potential bacteraemia. 

Data from Cotucci VV) Braunwald E. Pathophysiology of heart failure, in Braunwald E, Zipes DP, Libby P, eds. Eleart Disease A Eextbook of Cardiovascular Medicine, 6th ed. Philadelphia, Saunders, 2001 -.503-533 and Wynne j, Braunwald E. The cardiomyopathies and myocarditides. in Braunwald f> Zipes DP, Libby P, eds. Heart Disease A Textbook of Cardiovascular Medicine, 6th ed. Philadelphia, Saunders, 2001 1751-1806. 

The treatment of restrictive cardiomyopathy is complex becanse of the heterogeneity of the pathophysiologic abnormalities. Dinretics are used for the symptoms of venous congestion in the presence of restrictive cardiomyopathy, but caution is advised because these patients require high filling pressures to maintain an adequate stroke volume and cardiac output. Hypotension and hypoperfusion may occur as a result of the excessive use of diuretics. Because systolic function is often normal, digoxin is of little benefit and may be proarrhyth-... 

Mast cells are found in the human heart [31, 52], around coronary arteries [53], and in the coronary intima [54], Human heart mast cells have been implicated in the pathophysiology of myocarditis [55, 56], coronary artery diseases [53] and dilated cardiomyopathy [57], Finally, mast cells, through the release of vasoactive mediators, are also involved in systemic vasculitis [39],... 

Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008 5(1) 22-9. 

Litvinov IV, Kotowycz MA, Wassmann S. Iatrogenic epinephrine-induced reverse Takotsubo cardiomyopathy direct evidence supporting the role of catecholamines in the pathophysiology of the broken heart syndrome Clin Res Cardiol 2009 98(7) 457-62. 

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