Cardiomyopathy treatment

DEFINITE = Defibrillators in Non-lschemic Cardiomyopathy Treatment Evaluation Investigators. 

The DEFINITE (The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation)... 

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. 

Risk stratification of patients with nonischemic cardiomyopathy has proven to be more challenging than in their counterparts with CAD. The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation... 

Arguably, ICDs for primary prevention has greater benefit for the entire population than ICDs for secondary prevention. Several key primary prevention trials have been completed M IT, MUSTT, CABG-Patch (Coronary Artery Bypass Graft surgery), MADIT II, DINAMIT (Defibrillator in Acute Myocardial Infarction Trial), DEFINITE (Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation), SCD-HeFT, CAT (CArdiomyopathy Trial), and AMIOVERT (AMIOdarone VERsus implanv cardioverTer-defibrillator) trials (Table 14.4) (54,119,172-174). 

Inappropriate therapy is the most common adverse event associated with ICDs (53). With the first generation of ICDs (Ventak 1500,1550, inappropriate shocks ranged from 15-25%. Unfortunately, the frequency of inappropriate therapy with the latest generation of devices is probably similar (5). In the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Trial, that evaluated the use of ICDs in patients with nonischemic cardiomyopathy, inappropriate therapy was more likely than appropriate therapy (22 versus 18%) (78). A case of an inappropriate shock due to noise oversensing inducing ventricular fibrillation and subsequent death in a patient has been reported (79). Finally it is important to confirm from the device that therapies were in fact delivered phantom shocks are not uncommon, occurring in approximately 6-7% of people (80). 

From a therapeutic point of view, selective agonists may become useful in the treatment of heart failure and catecholamine-insensitive cardiomyopathy, but only if compounds become available that do not stimulate gastric acid secretion or cause other unforeseen problems. 

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. 

Emetine emetine is still used at high doses for the treatment of patients with severe amebiasis. Muscle damage is uncommon but when it does occur can be a severe generalized necrotizing myopathy. The outcome is, at times, fatal, especially when an emetine-induced cardiomyopathy is also present. Despite the suggestion that there may be neuritic changes, there is no evidence that emetine damages peripheral nerve. The myopathy is usually painful but reversible. The mechanism of action of emetine is unknown. 

Treatment of the acute phase of the disease (i.e., fever, malaise, edema of the face, and hepatosplenomegaly) is nifurtimox. The congestive heart failure associated with cardiomyopathy of Chagas disease is treated the same way as cardiomyopathy from other causes. 

Idarubicin inhibits both DNA and RNA polymerase, as well as topoisomerase II. The pharmacokinetics of idarubicin can best be described by a three-compartment model, with an a half-life of 13 minutes, a (3 half-life of 2.4 hours, and a terminal half-life of 16 hours.22 Idarubicin is metabolized to an active metabolite, idarubicinol, which has a half-life of 41 to 69 hours. Idarubicin and idarubicinol are eliminated by the liver and through the bile. Idarubicin has shown clinical activity in the treatment of acute leukemias, chronic myelogenous leukemia, and myelodysplastic syndromes. Idarubicin causes cardiomyopathy at cumulative doses of greater than 150 mg/m2 and produces cumulative cardiotoxic effects with other anthracyclines. Idarubicin is a vesicant and causes red-orange urine, mucositis, mild to moderate nausea and vomiting, and bone marrow suppression. 

In leukemia, the intensified use of methotrexate and glucocorticoids is responsible for causing an increased frequency of neurotoxicity and, in older children and adults, avascular necrosis of bone. High cumulative doses of anthracyclines can cause cardiomyopathy. Cranial irradiation causes neuropsychologic deficits and endocrine abnormalities that lead to obesity, short stature, precocious puberty, and osteoporosis.3 As newer and more intensive treatments enter clinical trials, close observation for long-term side effects will assume even greater importance.24... 

Oral ulcers Severe oral ulcers occurred in approximately 3% of patients in 2 trials. Less severe oral ulcerations occurred at higher frequencies in other clinical trials. Esophageal ulcers Infrequent cases of esophageal ulcers have been attributed to zalcitabine therapy. Consider interruption of therapy in patients who develop esophageal ulcers that do not respond to specific treatment for opportunistic pathogens in order to assess a possible relationship to zalcitabine. Cardiomyopathy/CHF Cardiomyopathy and CHF have occurred with the use of nucleoside antiretroviral agents in AIDS patients infrequent cases have occurred in patients receiving zalcitabine. Approach treatment with caution in patients with baseline cardiomyopathy or history of CHF. 

Pachon JC, Pachon El, Albornoz RN, et al. Ventricular endocardial right bifocal stimulation in the treatment of severe dilated cardiomyopathy heart failure with wide QRS. Pacing Clin. Electrophysiol. 2001 24 1369-76. 

Clinical trials of skeletal myoblasts have focused on the treatment of patients with ischemic cardiomyopathy and systolic dysfunction. Overall, these trials have resulted in improved segmental contractility and global LVEF. The preferred delivery route has been surgical intramyocardial injection, and one feasibility trial of transendocardial injection has been reported in the literature so far. 

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. 

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 angina pectoris, idiopathic cardiomyopathy... 

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... 

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