digoxin and Cardiomyopathy--Hypertrophic

Topics: Biomarkers; Cardenolides; Cardiomyopathy, Hypertrophic; Digoxin; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Humans; Myocardial Contraction; Myocardium; Prognosis; Saponins; Sarcomeres; Sodium-Potassium-Exchanging ATPase; Ventricular Pressure

Multifocal atrial tachycardia (MAT) has a well-known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Nonreentrant atrial tachycardias may cause cardiac compromise if sinus rhythm is not restored expeditiously. Typical first-line supraventricular tachycardia anti-arrhythmics (propranolol and digoxin) were generally not effective in restoring or maintaining sinus rhythm in this cohort, while flecainide or amiodarone alone or in concert with propranolol were effective anti-arrhythmic agents for acute and chronic use. Atrial tachycardia resolved in all patients. However, a 4-month-old boy from the cohort was found asystolic (with concurrent cellulitis) and a second patient underwent cardiac transplant for heart failure complicated by recalcitrant atrial arrhythmia. While propranolol alone frequently failed to convert or maintain sinus rhythm, fleccainide or amiodarone, occasionally in combination with propranolol, was effective for RASopathy patient treatment for nonreentrant atrial arrhythmia. Our analysis shows that RASopathy patients may have nonreentrant atrial tachycardia with and without associated cardiac hypertrophy. While nonreentrant arrhythmia has been traditionally associated with Costello syndrome, this work provides an expanded view of RASopathy cardiac arrhythmia phenotype as we demonstrate mutant proteins throughout this signaling pathway can also give rise to ectopic and/or MAT.

Topics: Amiodarone; Arrhythmias, Cardiac; Calcium; Cardiomyopathy, Hypertrophic; Costello Syndrome; Digoxin; Female; Humans; Infant; Infant, Newborn; LEOPARD Syndrome; Male; Noonan Syndrome; Propranolol; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Proto-Oncogene Proteins c-raf; Proto-Oncogene Proteins p21(ras); ras Proteins; SOS1 Protein; Tachycardia, Ectopic Atrial

Little is presently known regarding whether a rhythm-control or a rate-control strategy is more frequently used in patients hospitalized for atrial fibrillation (AF). This study was conducted to assess patient and physician characteristics associated with each treatment strategy and with the use of anticoagulants. Hospitalizations for primary diagnoses of AF were examined using hospital claims from January 2000 to December 2004. Patients who received antiarrhythmic drugs, ablation, or cardioversion for AF were categorized as receiving rhythm control. Patients managed only with beta blockers, calcium channel blockers, or digoxin were categorized as receiving rate control. Characteristics associated with rhythm compared with rate control and anticoagulant use with CHADS(2) score were determined. The study cohort included 155,731 hospitalizations from 464 hospitals. Of these, 75,397 (48%) were categorized as involving rhythm control and 80,334 (52%) as involving rate control. Care by a noncardiologist (adjusted odds ratio [OR] 0.33, 95% confidence interval [CI] 0.31 to 0.36) and increasing age >65 years (adjusted OR 0.87, 95% CI 0.86 to 0.88) were associated with lower odds of rhythm versus rate control; hypertrophic cardiomyopathy was associated with greater odds (adjusted OR 2.3, 95% CI 1.81 to 2.84) of rhythm control. Warfarin use was greater in the rhythm-control group compared with the rate-control group (adjusted OR 1.56, 95% CI 1.52 to 1.60), and warfarin use was greater with a CHADS(2) score > or =2 (unadjusted OR 1.21, 95% CI 1.19 to 1.24). In conclusion, rhythm- and rate-control strategies were used equally in patients hospitalized for AF. Some observations, such as greater use of the rate-control strategy with increasing age, were consistent with recommendations, but others, such as lower use of warfarin in the rate-control group, were not.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Catheter Ablation; Digoxin; Drug Utilization; Electric Countershock; Female; Hospitalization; Humans; Male; Medicine; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Severity of Illness Index; Specialization; United States; Warfarin; Wolff-Parkinson-White Syndrome

Although increased digitalis-like immunoreactive substances have been found in cases of hypertension and heart failure, no information is available about digitalis-like immunoreactive substances in patients with hypertrophic cardiomyopathy. We investigated digitalis-like immunoreactive substances in the plasma and biopsied specimens of patients with hypertrophic cardiomyopathy.. In 40 patients with hypertrophic cardiomyopathy (27 with the non-obstructive type and 13 with the obstructive type), the plasma concentration of digitalis-like immunoreactive substances was studied by fluorescence polarization immunoassay. Right ventricular endomyocardial biopsy specimens were analysed immunohistochemically, using a monoclonal antibody against digoxin. An increase in digitalis-like immunoreactive substances of more than 0.2 ng. ml(-1)in plasma was found in six of 27 patients with non-obstructive hypertrophic cardiomyopathy (22.2%) and five of 13 with obstructive hypertrophic cardiomyopathy (38.4%). Under light microscopy, positive staining against the antibody was observed heterogeneously on some cardiocytes. In non-obstructive hypertrophic cardiomyopathy, digitalis-like immunoreactive substances in the plasma correlated with the left atrial dimension and inversely with the cardiac index. In obstructive hypertrophic cardiomyopathy, plasma and myocardial digitalis-like immunoreactive substances were positively correlated; they also correlated with left ventricular end-diastolic pressures. Under electron microscopy, digitalis-like immunoreactive substances were detected at the sarcolemma in the free wall, T-tubules, intercalated discs and Z-bands of cardiocytes.. Increased digitalis-like immunoreactive substances in plasma and cardiocytes, which may have been caused by pressure and/or volume overload, were found in patients with hypertrophic cardiomyopathy. Digitalis-like immunoreactive substances may act on the sarcolemma of cardiocytes and be transported into the cytoplasm.

Topics: Adult; Aged; Antibodies, Monoclonal; Cardenolides; Cardiomyopathy, Hypertrophic; Digoxin; Female; Fluorescence Polarization Immunoassay; Hemodynamics; Humans; Immunohistochemistry; Male; Middle Aged; Myocardium; Saponins; Sodium-Potassium-Exchanging ATPase

Atrial fibrillation is the commonest arrhythmia observed in hypertrophic cardiomyopathy, and is associated with an acute deterioration in symptoms. Digoxin is the drug of choice in established atrial fibrillation and amiodarone the drug of choice in paroxysmal atrial fibrillation and ventricular arrhythmia. Non-sustained ventricular tachycardia occurs in 20% of patients and is the single best predictor of sudden death in adults. Sustained monomorphic ventricular tachycardia occurs only rarely. The mechanism of sudden death is likely to involve initiating factors such as arrhythmia and peripheral autonomic dysfunction causing haemodynamic instability and myocardial ischaemia. Myocardial disarray may provide the arrhythmogenic substrate such that haemodynamic instability and ischaemia results in ventricular fibrillation and sudden death.

Topics: Amiodarone; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Digoxin; Electrocardiography; Humans; Tachycardia, Ventricular

Topics: Age Factors; Arteriosclerosis; Cardiomyopathy, Hypertrophic; Digoxin; Furosemide; Heart Failure; Humans; Hypertension; Infant; Male; Radiography

When fed furazolidone, 700 ppm, with their mash, most turkey poults develop dilated cardiomyopathy characterized by gross left ventricular dilatation with thinning of both the left ventricular free wall and ventricular septum. Birds fed propranolol, but not digoxin, did not develop this cardiomyopathy. It is not known what pharmacologic property of propranolol conferred protection or if mammals would receive similar protection.

Topics: Animals; Cardiomyopathy, Hypertrophic; Digoxin; Furazolidone; Poultry Diseases; Propranolol; Turkeys

Retrospective analysis of the clinical course of 254 patients with hypertrophic cardiomyopathy, followed up for 1 to 23 years (mean 6), disclosed that 58 had died, 32 of them suddenly. The 196 survivors were compared with the 32 patients who died suddenly and with the 38 who died suddenly or with heart failure. The combination of young age (14 years or less), syncope at diagnosis, severe dyspnea at last follow-up and a family history of hypertrophic cardiomyopathy and sudden death best predicted sudden death (false negative rate 30 percent, false positive rate 27 percent). A "malignant" family history was associated with poor prognosis, particularly in the younger patients; a family history of hypertrophic cardiomyopathy without sudden death was more frequent in the survivors (12 percent) than in the dead (5 percent). Patients who had a diagnosis in childhood were usually asymptomatic, had an unfavorable family history and a 5.9 percent annual mortality rate. In those aged 15 to 45 years at diagnosis, there was a 2.5 percent annual mortality rate and syncope was the only prognostic feature. Among those diagnosed between age 45 and 60 years, dyspnea and exertional chest pain were more common in the patients who died, and the annual mortality rate was 2.6 percent. Poor prognosis was better predicted by the history at the time of diagnosis and by changes in symptoms during follow-up than by an electrocardiographic or hemodynamic measurement.

Topics: Adolescent; Adult; Aged; Aging; Anti-Arrhythmia Agents; Cardiomyopathy, Hypertrophic; Child; Child, Preschool; Death, Sudden; Digoxin; Electrocardiography; Female; Follow-Up Studies; Hemodynamics; Humans; Male; Middle Aged; Prognosis

On the patients with moderate and severe heart insufficiency haemodynamic, clinical and electrocardiographic examinations were carried out. After the application of digitoxin at the beginning in the majority of cases no favourable effects on clinical and haemodynamic findings could be proved. In 2 patients with cor pulmonale even a drastic deterioration with increase of the pulmonary pressure and formation of a pulmonary oedema developed. The temporary analysis of the systole and the estimation of the glycoside level did not give any reliable references. The recompensation began only after 2-3 days. In 5 out of 10 patients in whom the cardiac rhythm was continuously controlled by means of a tape storage device, after the application of digoxin ventricular extrasystoles appeared. Also in these cases increased as well as subtherapeutic digoxin-plasma levels were present. In 2 patients with hypertrophic obstructive cardiomyopathy the infundibular gradients were considerably increased by strophantin. The causes of the different reaction patters are to be sought in disease-specific peculiarities, in the degree of severity of the heart insufficiency, in the speed of the flooding of glycoside and several extracardiac factors.

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Blood Pressure; Cardiac Complexes, Premature; Cardiomyopathy, Hypertrophic; Digitalis Glycosides; Digoxin; Female; Heart; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Pulmonary Edema; Pulmonary Heart Disease

Using the recipient's human heart removed at cardiac transplantation, the distribution of digoxin at both the cellular and subcellular level has been studied. In the presence of diffuse histological myocardial abnormalities tissue digoxin is decreased, but the subcellular distribution, presumably reflecting binding to a possible receptor site, is uniform. When the histological abnormality is focal then digoxin distribution is uniform.These results suggest that in the presence of myocardial ischaemia plasma digoxin concentrations may not reflect total myocardial levels accurately.

Topics: Adenosine Triphosphatases; Adult; Blood Urea Nitrogen; Cardiomyopathy, Hypertrophic; Coronary Disease; Digoxin; Female; Heart Atria; Heart Transplantation; Heart Ventricles; Humans; Magnesium; Male; Microsomes; Middle Aged; Myocardium; Potassium; Radioimmunoassay; Sodium; Transplantation, Homologous

Topics: Aortic Valve; Cardiac Catheterization; Cardiomyopathy, Hypertrophic; Chlordiazepoxide; Digitalis Glycosides; Digoxin; Female; Heart Block; Humans; Hydrochlorothiazide; Hypotension; Middle Aged; Phonocardiography; Pulse

Topics: Alcohol Drinking; Anticoagulants; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Diet, Sodium-Restricted; Digitalis; Digoxin; Diuretics; Ethanol; Female; Heart; Heart Failure; Humans; Male; Phytotherapy; Plants, Medicinal; Plants, Toxic; Practolol; Pregnancy; Propranolol; Rest

Topics: Angiocardiography; Autopsy; Cardiac Catheterization; Cardiomyopathy, Hypertrophic; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Heart Ventricles; Humans; Infant; Infant, Newborn; Male; Myocardium; Pulmonary Valve; Pulmonary Valve Stenosis

Topics: Acetanilides; Adrenergic beta-Antagonists; Amino Alcohols; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Digoxin; Hemodynamics; Humans; Isoproterenol; Propranolol