Medication Summary
No cardiac medications resolve the problem of hypertrophic cardiomyopathy (HCM), particularly in Danon disease. However, standard medications for congestive heart failure (CHF) and arrhythmias should be used as they are in other patients with these conditions. For Danon disease with HCM, no medical treatment is indicated unless the patient has symptoms of CHF or angina. On the contrary, patients with dilated cardiomyopathy should be given anti-CHF medications.
No medications are known to resolve or ease the neuromuscular symptoms of Danon disease.
To the authors' knowledge, no reports have demonstrated successful experience with any of the antiarrhythmic agents used in Danon disease. However, treatment of supraventricular tachycardia (SVT) should begin with beta-blockers. Digoxin and verapamil should be avoided when evidence suggests the presence of Wolff-Parkinson-White syndrome. Although ablation may be indicated, other antiarrhythmic medications (eg, propafenone, disopyramide, amiodarone, sotalol) may be helpful to control SVT if ablation is not possible or desired. The beneficial effects or adverse effects of these medications, when used in Danon disease, have not been established.
Diuretic agents
Class Summary
These drugs are indicated for CHF due to systolic or diastolic dysfunction.
Furosemide (Lasix)
Loop diuretic that increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Increases renal blood flow without increasing filtration rate. Onset of action generally within 1-h. Increases potassium, sodium, calcium, and magnesium excretion.
Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after previous dose, until desired diuresis occurs. In infants, titrate with 1-mg/kg/dose increments until satisfactory effect achieved.
Diuretics have major clinical uses in managing disorders involving abnormal fluid retention (edema) or in treating hypertension; diuretic action decreases blood volume.
PO administration less potent diuretic effect than IV administration.
Spironolactone (Aldactone)
Potassium-sparing diuretic. Indicated for management of edema resulting from excessive aldosterone excretion. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.
Beta blockers
Class Summary
These agents are indicated for the management of dilated cardiomyopathy.
Carvedilol (Coreg)
Used only for patients with dilated cardiomyopathy and CHF. Nonselective beta- and alpha-adrenergic blocker. Also has antioxidant properties. Does not appear to have intrinsic sympathomimetic activity. May reduce cardiac output and decrease peripheral vascular resistance.
Metoprolol (Lopressor)
Indicated for dilated cardiomyopathy. Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions.
ACE inhibitors
Class Summary
These agents reduce afterload in dilated cardiomyopathy and/or CHF.
Enalapril (Vasotec)
Prevents conversion of angiotensin I to angiotensin II (potent vasoconstrictor), increasing levels of plasma renin and reducing aldosterone secretion. Helps control blood pressure and proteinuria. Decreases pulmonary-to-systemic flow ratio in catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. Favorable clinical effect when administered over a long period. Helps prevent potassium loss in distal tubules. Body conserves potassium; therefore, less PO potassium supplementation needed.
Patients who develop a cough, angioedema, bronchospasm, or other hypersensitivity reactions after starting ACE inhibitors should receive an angiotensin-receptor blocker.
Captopril (Capoten)
Prevents conversion of angiotensin I to angiotensin II (potent vasoconstrictor), lowering aldosterone secretion. Rapidly absorbed, but bioavailability significantly reduced with food intake. Peak concentration in 1 h; has short half-life. Cleared by kidney. Can be started at low dose and uptitrated prn and as patient tolerates.
Impaired renal function requires reduced dosage. Absorbed well PO. Give at least 1 h before meals. If added to water, use within 15 min.
Accepted as essential part of any antifailure therapy; provides symptomatic improvement and prolongs survival.
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Echocardiogram of a patient with Danon disease and severe hypertrophy. The septum is between the arrows. Note the asymmetry between the septum and the posterior wall of the left ventricle. Also see Media files 2-3. Calibration markings are in centimeters. Ao = ascending aorta just above the aortic valve; LV = left ventricle; LVPW = left ventricular posterior wall.
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Echocardiogram, short-axis view in diastole, in the same patient as in Media files 1 and 3. Because of the degree of hypertrophy, the cavitary volume is smaller than normal. Calibration markings are in centimeters. Ao = ascending aorta just above the aortic valve; LV = left ventricle; LVPW = left ventricular posterior wall.
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Echocardiogram, short-axis view in systole, in the same patient as in Media files 1-2. Note the increased thickening of the septum. Calibration markings are in centimeters. Ao = ascending aorta just above the aortic valve; LV = left ventricle; LVPW = left ventricular posterior wall.
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Horizontal ventricular sections of the heart from 16-year-old male adolescent with Danon disease obtained after orthotopic cardiac transplantation. Massive hypertrophy is present (heart weight, 785 g), with diffuse severe fibrosis and marked ventricular dilatation.
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Myocyte hypertrophy and vacuolization with interstitial fibrosis in the myocardium of a heart removed during cardiac transplantation (periodic acid-Schiff [PAS] stain; original magnification, X400).
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Electron photomicrograph shows autophagic vacuoles with glycogen in a heart removed during cardiac transplantation (uranyl acetate and Reynolds lead citrate; original magnification X20,000).
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Electron photomicrograph shows increased amounts of intermyofibrillar glycogen in the myocardium (uranyl acetate and Reynolds lead citrate; original magnification, X13,000).
