digoxin and Ataxia

The dilated cardiomyopathy with ataxia syndrome (DCMA) is a rare mitochondrial disorder characterized by progressive cardiomyopathy, prolonged QT interval and early death in childhood related to intractable heart failure. We present a case series of 9 children with DCMA who demonstrated functional improvement and favourable left ventricular remodeling only after digoxin was added to their medical therapy.. A retrospective review of 46 patients with DCMA followed at the Alberta Children's Hospital from 2005 to 2017 identified 9 patients who were treated with digoxin and had serial echocardiography data. For each subject, we calculated the difference between baseline and follow-up for left ventricular ejection fraction (LVEF), end-diastolic dimension (LVEDD), and end-systolic dimension (LVESD) as determined by echocardiography.. Patients were on average 45.6 ± 59 months of age when digoxin was started with a mean LVEF of 40% ± 11% when digoxin was started. Seven patients were on angiotensin-converting enzyme inhibitors (ACEIs) at the time of initiation of digoxin, and all were on β-receptor antagonists (BB). After being on digoxin for a mean of 11.7 ± 10.9 months, average LVEF improved to 55% ± 10% (P = 0.0005), and there were significant decreases in the Z-scores for LVEDD (+2.1 ± 1.9 to +0.65 ± 1.4, P = 0.02) and LVESD (+3.83 ± 2.07 to +1.79 ± 1.76, P = 0.01).. In children with DCMA, we report that digoxin seems to have additive beneficial properties when combined with ACEI and BB therapy. This novel observation may have implications for the medical treatment of mitochondrial cardiomyopathies.

Topics: Ataxia; Cardiomyopathy, Dilated; Cardiotonic Agents; Child, Preschool; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Infant; Male; Retrospective Studies; Stroke Volume; Syndrome; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

Topics: Ataxia; Cardiomyopathies; Cardiomyopathy, Dilated; Child; Digoxin; Humans; Syndrome

3 beta,5,14-Trihydroxy-19-oxo-5 beta-bufa-20,22-dienolide 3-(3-methylcrotonate) (acrihellin, D 12 316) is according to chemical structure and pharmacological effects a semisynthetic compound of the aglycon hellebrigenin. It is characterized as a cardiosteroid. In isolated organ (Langendorff heart) the positive inotropic effect proved to be stronger in comparison to digoxin. Also in dogs and cats acrihellin increases the contractile force of the myocardium; especially in failing canine heart, it increases the force of contraction (strain-gauge) and velocity of pressure rise (dp/dt max). In classical glycoside test on cat (Hatcher's dose) acrihellin is more effective than digoxin and methyldigoxin on weight basis, equivalent on a molar basis. The therapeutical index of acrihellin is like that of methyldigoxin. In cats and dogs, the compound is absorbed rapidly and almost completely, especially when administered intraduodenally. Herein it is comparable to methyldigoxin, better than digoxin. In cats acrihellin shows a decay rate of 26%. In all investigations performed in order to study central nervous effects after single administration of therapeutical doses no central side-effects could be detected in contrast to methyldigoxin.

Topics: Anesthesia; Animals; Anticonvulsants; Ataxia; Bufanolides; Cardiac Glycosides; Cats; Digoxin; Dogs; Female; Gastrointestinal Motility; Guinea Pigs; Hemodynamics; Hexobarbital; In Vitro Techniques; Male; Mice; Motor Activity; Myocardial Contraction; Rats; Reflex; Sleep; Stomach Ulcer

Topics: Ataxia; Cerebellar Diseases; Coma; Digoxin; Humans; Male; Middle Aged; Phenytoin