Doses Of Digitalis Research Articles

Strofantin and novazurol for heart disease

Weiss (Deut, med Woch., 1924 No. 33) reports on his observations on the treatment of severe cardiac patients with strophanthin and novosurol. In chronic heart diseases in a state of sharp decompensation, sometimes digitalis has no effect, especially when the body, due to the prolonged use of small doses of digitalis, has become accustomed to this remedy.

Ouabain prevents pathological cardiac hypertrophy and heart failure through activation of phosphoinositide 3-kinase α in mouse.

Background Use of low doses of digitalis to prevent the development of heart failure was advocated decades ago, but conflicting results of early animal studies dissuaded further research on this issue. Recent discoveries of digitalis effects on cell signal pathways prompted us to reexamine the possibility of this prophylactic action of digitalis. The specific aim of the present study was to determine if subinotropic doses of ouabain would prevent pressure overload-induced cardiac remodeling in the mouse by activating phosphoinositide 3-kinase α (PI3Kα).ResultsStudies were done on an existing transgenic mouse deficient in cardiac PI3Kα (p85-KO) but with normal cardiac contractility, a control mouse (Con), and on cultured adult cardiomyocytes. In Con myocytes, but not in p85-KO myocytes, ouabain activated PI3Kα and Akt, and caused cell growth. This occurred at low ouabain concentrations that did not activate the EGFR-Src/Ras/Raf/ERK cascade. Con and p85-KO mice were subjected to transverse aortic constriction (TAC) for 8 weeks. A subinotropic dose of ouabain (50 µg/kg/day) was constantly administrated by osmotic mini-pumps for the first 4 weeks. All mice were monitored by echocardiography throughout. Ouabain early treatment attenuated TAC-induced cardiac hypertrophy and fibrosis, and improved cardiac function in TAC-operated Con mice but not in TAC-operated p85-KO mice. TAC downregulated α2-isoform of Na+/K+-ATPase but not its α1-isoform in Con hearts, and ouabain treatment prevented the downregulation of α2-isoform. TAC-induced reduction of α2-isoform did not occur in p85-KO hearts.ConclusionsOur results show that (a) safe doses of ouabain prevent or delay cardiac remodeling of pressure overloaded mouse heart; and (b) these prophylactic effects are due to ouabain binding to α2-isoform resulting in the selective activation of PI3Kα. Our findings also suggest that potential prophylactic use of digitalis for prevention of heart failure in man deserves serious consideration.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-015-0053-7) contains supplementary material, which is available to authorized users.

Digitalis for treatment of heart failure in patients in sinus rhythm.

Digitalis glycosides have been in clinical use for the treatment of heart failure (HF) for longer than 200 years. In recent years, several trials have been conducted to address concerns about their efficacy and toxicity. To examine the effectiveness of digitalis glycosides in treating HF in patients with normal sinus rhythm. To examine the effects of digitalis in patients taking diuretics and angiotensin-converting enzyme inhibitors; in patients with varying severity and duration of disease; in patients with prior exposure to digitalis versus no prior exposure; and in patients with "HF due to systolic dysfunction" versus "HF with preserved ejection fraction." Searches on the following databases were updated in May 2013: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Dissertation Abstracts. Annual meeting abstracts of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology were searched from 1996 to March 2013. In addition, reference lists provided by the pharmaceutical industry (GlaxoSmithKline and Covis Pharma) were searched. Included were randomized placebo-controlled trials of 20 or more adult participants of either sex with symptomatic HF who were studied for seven weeks or longer. Excluded were trials in which the prevalence of atrial fibrillation was 2% or greater, or in which any arrhythmia that might compromise cardiac function or any potentially reversible cause of HF such as acute ischemic heart disease or myocarditis was present. Articles selected from the searches described above were evaluated in a joint effort of the review authors. The staff of the Cochrane Heart Group ran searches on the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. No new studies were identified in the updated searches. Thirteen studies (7896 participants) are included, and major endpoints of mortality, hospitalization, and clinical status, based respectively on 8, 4, and 12 of these selected studies, were recorded and analyzed. The data show no evidence of a difference in mortality between treatment and control groups, whereas digitalis therapy is associated with lower rates of both hospitalization and clinical deterioration. The largest study, in which most participants were taking angiotensin-converting enzyme inhibitors, showed a significant rise in "other cardiac" deaths, possibly due to arrhythmias. However collectively, these findings were based on studies done before beta-blockers, as well as angiotensin receptor blockers and aldosterone antagonists, became widely used to treat HF. The literature indicates that digitalis may have a useful role in the treatment of patients with HF who are in normal sinus rhythm. New trials are needed to elucidate the importance of the dosage of digitalis and its usefulness in the era of beta-blockers and other agents shown to be effective in treating HF.

Landmark Publication from The American Journal of the Medical Sciences: The Clinical Pharmacology of Digitalis Glycosides: A Review

The metabolic half-times and excretion rates of labeled cardiac glycosides are related to pharmacologic or therapeutic activity. Digoxin, a short-acting glycoside, is excreted primarily in the urine and has a serum half-time of 34hours. This function is related primarily to digoxin excretion. Digitoxin, a long-acting glycoside, has a serum half-time of 50+ hours and a physiologic half-time of 51/2 days. It is excreted primarily in the urine as metabolites of the parent compound. Renal failure compromises digoxin excretion and prolongs the digoxin serum half-time and thereby the pharmacologic activity of the drug. As excretion is related to creatinine clearance, dosage should be reduced in proportion to reduction in creatinine clearance in renal insufficiency. Hyper-thyroid patients have lower digoxin serum levels and hypothyroid patients higher digoxin serum levels when compared to euthyroid patients. This finding confirms the clinical impression of digitalis resistance in hyperthyoidism and sensitivity in myxe-dema. Appropriate alterations in digoxin dosage in thyroid disease are justified. Patients with liver disease and cor pulmonale have normal digoxin serum levels, half-times and excretion rates. Increased digitalis sensitivity in these patients is related to other factors. Knowledge of the serum half-time, route of excretion, and rate of excretion of the cardiac glycosides is now available. Application of this information to the patient receiving digitalis assists in avoiding over- and under-digitalization—both common clinical problems. If doubt exists regarding digitalis dosage, smaller, rather than larger, doses are suggested to avoid toxicity.

Edwin Leigh Newcomb 1882-1950: Pharmacy's many-sided man

Edwin Leigh Newcomb 1882-1950: Pharmacy's many-sided man

Comparison of digitalis-related adverse events in hospitalized men and women in Italy: An observational study

Background: A higher mortality rate in women thanin men treated with digitalis has been described. We hypothesized that this result could be due in part to an increased susceptibility of women to adverse events (AEs) from digitalis. Objective: The aim of this study was to compare theincidence of AEs related to digitalis in women and men. Methods: This was an observational study conducted in geriatrics and internal medicine acute-care wards located throughout Italy. We used the data of the Gruppo Italiano di Farmacoepidemiologia nell'Anziano (Italian Group of Pharmacoepidemiology in the Elderly), a collaborative study group on drug use and adverse drug reactions in hospitalized adults that performed 6 different surveys between 1988 and 1998. Adults who were taking digitalis at the time of admission or during the hospital stay were studied, with no other inclusion or exclusion criteria. The proportion of AEs to digitalis diagnosed at the time of admission or during the hospital stay was compared in men and women. Information on AEs was collected using a structured questionnaire at admission and during the hospital stay. A logistic regression model was used to evaluate the association between sex and AE(s) to digitalis, corrected for potential confounding variables. Results: The total sample size was 9626 patients.Women received a higher weight-adjusted dose of digitalis compared with men (0.0027 mg/kg per day vs 0.0025 mg/kg per day; P < 0.001). Overall, 199 AEs to digitalis were diagnosed. Women were more likely than men to suffer from an AE to digitalis (odds ratio, 1.51; 95% CI, 1.12–2.02). This finding was confirmed after correction for dose of digitalis, age, physical and cognitive impairment, atrial fibrillation, chronic obstructive pulmonary disease, glomerular filtration rate, and use of amiodarone, β-blockers, nondihydropyridine calcium channel blockers, and potassium-sparing diuretics (odds ratio, 1.58; 95% CI, 1.01–2.48). Conclusions: In this sample of hospitalized adults in Italy, we found a higher incidence of AEs to digitalis in women than in men.

Enhanced Automaticity of the His Bundle

Scenario: This ECG was obtained in a 70-year-old female patient being treated for new onset atrial fibrillation on the telemetry unit. The patient has been given several doses of digitalis for her atrial fibrillation. Currently the patient is asymptomatic. ECG PUZZLER A regular feature of the American Journal of Critical Care, the ECG Puzzler addresses ECG interpretation for clinical practice. We welcome letters to the Editors regarding this feature.

Dosage of ACE‐inhibitors, diuretics and digitalis for the treatment of congestive heart failure given by general practitioners in teh province Styria in Austria

European Journal of Heart FailureVolume 2, Issue S1 p. 98-98 AbstractsFree Access Dosage of ACE-inhibitors, diuretics and digitalis for the treatment of congestive heart failure given by general practitioners in teh province Styria in Austria M. Wonisch, M. Wonisch Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this authorF.M. Fruhwald, F.M. Fruhwald Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this authorR. Maier, R. Maier Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this authorN. Watzinger, N. Watzinger Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this authorW. Klein, W. Klein Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this author M. Wonisch, M. Wonisch Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this authorF.M. Fruhwald, F.M. Fruhwald Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this authorR. Maier, R. Maier Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this authorN. Watzinger, N. Watzinger Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this authorW. Klein, W. Klein Dep. of Internal Medicine, LKH Graz, Graz, AustriaSearch for more papers by this author First published: 19 May 2004 https://doi.org/10.1016/S1388-9842(00)80349-9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume2, IssueS1June 2000Pages 98-98 RelatedInformation

Nebivolol in the treatment of cardiac failure: A double-blind controlled clinical trial

Background: Nebivolol is a highly cardioselective long-acting beta-blocker with vasodilating properties, which acts in part via the endothelial l-arginine/nitric oxide pathway. As an antihypertensive drug it is effective in once-daily dosage. Nebivolol has previously been shown to improve left ventricular function in patients with cardiac impairment. Methods and Results: This paper reports a double-blind randomized trial comparing, in patients with heart failure, once-daily nebivolol 2.5 or 5.0 mg (initiated in all at 2.5 mg) with placebo on a constant background of digitalis plus diuretic. There was with nebivolol no overall deterioration of cardiac function or cardiac symptoms, and especially not of exercise capacity, in comparison with placebo. One patient on nebivolol 2.5 mg developed hypotension and pulmonary edema, and one patient on nebivolol 5 mg, bradycardia. All the remaining patients continued with unchanged diuretic and digitalis dosage. Nebivolol was accompanied by a trend toward clinical and functional improvement; rather better results were obtained with 2.5 than 5.0 mg. Conclusions: In view of increasing interest in beta-blockade in heart failure, nebivolol merits further study in this context. The capacity of nebivolol to enhance endothelial nitric oxide production appears potentially attractive.

Digitalis increases brain natriuretic peptide in patients with severe congestive heart failure

Ouabain can cause increased secretion of atrial natriuretic peptide (ANP) from atrial cardiocyte culture, but the effects of digitalis in a therapeutic range on the secretion of cardiac natriuretic peptide including ANP and brain natriuretic peptide (BNP), mainly from the ventricle, in patients with congestive heart failure remain to be investigated. Therefore we studied the acute effects of intravenous infusion of a relatively low dose of digitalis or placebo on hemodynamics and neurohumoral factors including the plasma levels of ANP and BNP and cyclic guanosine monophosphate, a second messenger of cardiac natriuretic peptide, in 13 patients with severe congestive heart failure. No significant change in the hemodynamic parameters or neurohumoral factors was observed with placebo. After 1 hour of intravenous administration of deslanoside (0.01 mg/kg), there was a significant decrease of plasma renin activity and angiotensin II, aldosterone, and norepinephrine levels but no significant change of plasma levels of vasopressin and a significant decrease of the pulmonary capillary wedge pressure but no significant change in cardiac index. In addition, plasma levels of ANP (217 +/- 47 vs 281 +/- 70 pg/ml, p < 0.05), BNP (628 +/- 116 vs 689 +/- 132 pg/ml, p < 0.05), and cyclic guanosine monophosphate (9.7 +/- 1.1 vs 10.9 +/- 1.5 pmol/ml, p < 0.05) increased despite the decrease of pulmonary capillary wedge pressure (19.7 +/- 2.3 vs 16.8 +/- 2.3 mm Hg, p < 0.05). These results indicate the acute intravenous low dose of digitalis resulted in a significant increase in plasma levels of ANP, BNP, and cyclic guanosine monophosphate concomitant with the significant decrease of pulmonary capillary wedge pressure, suggesting the acute direct action of digitalis on the cardiac natriuretic peptides released from the heart in patients with severe congestive heart failure.

Multifocal Atrial Tachycardia

Abstract Multifocal atrial tachycardia was seen in 32 elderly and severely ill patients, with a high prevalence of acute and chronic pulmonary disease and cor pulmonale. Twelve patients (37.5 per cent) died. Bronchodilators were used frequently and contributed to the rapid heart rates. The arrhythmia itself was rarely due to digitalis intoxication. Serious arrhythmias did not arise in patients receiving maintenance doses of digitalis. Increments of digitalis often produced high-grade atrioventricular block, atrial tachycardia with block, nodal rhythms and ventricular irritability. Multifocal atrial tachycardia should be carefully distinguished from other atrial arrhythmias, especially atrial fibrillation. This is particularly important for rational digitalis therapy. Control of the arrhythmia paralleled improvement in ventilation and oxygenation, control of sepsis, correction of metabolic and electrolyte derangements and reduction in chronotropic drugs used as bronchodilators. The role of antiarrhythmic a...

Effects of Increasing Maintenance Dose of Digoxin on Left Ventricular Function and Neurohormones in Patients With Chronic Heart Failure Treated With Diuretics and Angiotensin-Converting Enzyme Inhibitors

Despite almost three centuries of use, the appropriate dosage of digitalis in patients with chronic heart failure and normal sinus rhythm has not been well studied. We studied 22 patients with heart failure who were receiving constant daily doses of digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. In 18 patients, the oral daily dose of digoxin was increased from a mean of 0.20 +/- 0.07 to 0.39 +/- 0.11 mg/day corresponding to an increase in the serum digoxin concentration from 0.67 +/- 0.22 to 1.22 +/- 0.35 ng/mL. Radionuclide and echocardiographic left ventricular ejection fraction; maximal treadmill time; heart failure score; serum concentrations of norepinephrine, aldosterone, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity were obtained before and after the increase in digoxin dose. Subsequently, 9 patients were randomized to receive digoxin and 9 to receive placebo and radionuclide ejection fraction measured after 12 weeks. With the higher dose of digoxin compared with the lower dose, there was a significant increase in radionuclide ejection fraction from 23.7 +/- 9.6% to 27.1 +/- 11.8% (P = .007). No significant changes were noted in heart failure score; exercise tolerance; serum concentrations of norepinephrine, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity. There was, however, an increase in serum aldosterone concentration. Twelve weeks after the patients were randomized to receive digoxin or placebo, there was a significant decrease in ejection fraction (from 29.4 +/- 10.4% to 23.7 +/- 8.9%) in the placebo group but not in patients who continued to receive digoxin (P = .002). The increase in maintenance digoxin dose, while maintaining serum concentrations within therapeutic range, resulted in a significant increase in left ventricular ejection fraction that was not associated with significant changes in heart failure score, exercise tolerance, and neurohumoral profile.

Salutary effect of Terminalia Arjuna in patients with severe refractory heart failure

Twelve patients with refractory chronic congestive heart failure (Class IV NYHA), related to idiopathic dilated cardiomyopathy (10 patients); previous myocardial infarction (one patient) and peripartum cardiomyopathy (one patient), received Terminalia Arjuna, an Indian medicinal plant, as bark extract (500 mg 8-hourly) or matching placebo for 2 weeks each, separated by 2 weeks washout period, in a double blind cross over design as an adjuvent to maximally tolerable conventional therapy (Phase I). The clinical, laboratory and echocardiographic evaluation was carried out at baseline and at the end of Terminalia Arjuna and placebo therapy and results were compared. Terminalia Arjuna, compared to placebo, was associated with improvement in symptoms and signs of heart failure, improvement in NYHA Class (Class III vs. Class IV), decrease in echo-left ventricular enddiastolic (125.28 ± 27.91 vs. 134.56 ± 29.71 ml/m 2; P < 0.005) and endsystolic volume (81.06 ± 24.60 vs. 94.10 ± 26.42 ml/m 2; P < 0.005) indices, increase in left ventricular stroke volume index (44.21 ± 11.92 vs. 40.45 ± 11.56 ml/m 2; P < 0.05) and increase in left ventricular ejection fractions (35.33 ± 7.85 vs. 30.24 ± 7.13%; P < 0.005). On long term evaluation in an open design (Phase II), wherein Phase I participants continued Terminalia Arjuna in fixed dosage (500 mg 8-hourly) in addition to flexible diuretic, vasodilator and digitalis dosage for 20–28 months (mean 24 months) on outpatient basis, patients showed continued improvement in symptoms, signs, effort tolerance and NYHA Class, with improvement in quality of life. One patient died of cerebrovascular accident while another had sudden cardiac death, 16 months and 14 months after entry into Phase II, respectively. No significant clinical untoward effect occurred during Terminalia Arjuna or placebo therapy. The mechanism of beneficial effects of Terminalia Arjuna needs evaluation but it could be related to one or more of the constituents which have cardiotonic (glycosides) or free radicle scavenger (tannins, flavones) properties. In conclusion, adjuvent Terminalia Arjuna therapy in our patients with refractory congestive heart failure, mostly related to idiopathic dilated cardiomyopathy, appeared safe and caused long lasting improvement in symptoms and signs of heart failure along with improvement in left ventricular ejection phase indices with definite improvement in quality of life. We believe that these preliminary observations open a new vista for future research in therapy of myocardial failure.

Cardiac glycosides. Drug interactions of clinical significance.

Several commonly coadministered drugs interfere significantly with the pharmacokinetics or pharmacodynamics of cardiac glycosides. Only a few of these interactions (e.g. amiodarone, propafenone, quinidine) take place consistently, and although their extent may vary in individual patients, digitalis dosage adjustments should be made to avoid underdigitalization or toxicity. In other instances the appearance of clinically significant interactions depends on individual pharmacokinetic/metabolic characteristics (e.g. erythromycin, tetracycline), and the result cannot be anticipated on clinical grounds. Some interactions are controversial, having not been confirmed by all studies; others have been shown only in healthy volunteers but lack the definition of their relevance in the context of disease states. In view of the possible impact on the individual patient, close clinical monitoring (which may be supplemented with evaluation of digitalis plasma concentration) is recommended when prescribing cardiac glycosides with other therapeutic agents for which the possibility of an interaction has been reported.

Antiarrhythmic Effects of Bisaramil on Triggered Arrhythmias Produced by Intracoronary Injection of Digitalis and Adrenaline in the Dog

Antiarrhythmic effects of bisaramil were examined by using new in vivo triggered arrhythmia models, and they were compared with those of other antiarrhythmic drugs. Bisaramil (3–10 μg, i.e.) suppressed triggered ventricular arrhythmias that were produced during pauses between trains of rapid ventricular stimulation (cycle length: 250 msec, train number: 15) in anesthetized open-chest dog hearts administered with subtoxic doses of digitalis or adrenaline to the anterior descending coronary artery. The potencies of bisaramil, disopyramide, lidocaine and flecainide suppressing digitalis-induced triggered ventricular arrhythmias were similar to those suppressing adrenaline-induced ones. The potency of verapamil for suppressing digitalis-induced triggered ventricular arrhythmias were weaker than that for suppressing the adrenaline-induced ones. Bisaramil was the most effective among the antiarrhythmic drugs used in the present experiment. Since bisaramil has been reported to be effective in suppressing other canine automatic ventricular arrhythmias, and the triggered ventricular arrhythmias occur in clinical situations, bisaramil may become a useful drug for the treatment of clinical arrhythmias.

Antiarrhythmic effects of eicosapentaenoic acid during myocardial infarction--enhanced cardiac microsomal (Ca(2+)-Mg2+)-ATPase activity.

The effects of dietary supplementation with eicosapentaenoic acid (EPA) on ventricular arrhythmias during myocardial infarction were examined in a canine model. EPA was incorporated into cellular membranes after ingestion of EPA-ester (100 mg/kg body weight/day) for 8 weeks. The ratio of EPA to arachidonic acid (AA) in platelet cell membranes and myocardial microsomes was significantly increased (7% to 37% in platelet cell membranes; p < 0.01, 3% to 12% in non-infarcted cardiac microsomes; p < 0.01, and from 2% to 8% in infarcted cardiac microsomes; p < 0.01). Dietary supplementation with EPA significantly reduced the incidence and severity of arrhythmias during coronary artery occlusion. Immediately after coronary artery occlusion, all of the animals in the control group that were given a toxic dose of digitalis developed ventricular tachycardia (VT) or ventricular fibrillation (Vf), whereas none of the animals in the EPA-supplement group developed VT or Vf within 15 min after administration of digitalis. Regardless of the presence of an infarcted area, the specific activity of the Ca(2+)-pump enzyme ((Ca(2+)-Mg2+)-ATPase) within the myocardial microsomal fraction of the EPA-supplemented group was significantly higher than in that of the control group (Vmax: 140.5 +/- 19.1 vs 94.8 +/- 28.9 nmol/mg/min in non-infarcted cardiac microsomes, p < 0.01, 130.9 +/- 18.4 vs 90.2 +/- 26.4 nmol/mg/min in infarcted cardiac microsomes, p < 0.01, EPA vs control group, respectively). The specific activities of the Na(+)-pump enzyme ((Na(+)-K+)-ATPase) and NADPH-dependent cytochrome C reductase in infarcted and non-infarcted cardiac microsomes did not differ between these groups. These results indicate that EPA supplementation increases the (Ca(2+)-Mg2+)-ATPase activity within myocardial membranes that is involved in Ca2+ metabolism in myocardial cells by increasing the ratio of EPA to AA within cellular membranes. These cellular alterations are likely to reduce the severity of ventricular arrhythmias by inhibiting the rapid accumulation of intracellular Ca2+ following ischemia.

The development of positive inotropic agents for chronic heart failure: How have we gone astray?

Because cardiac contractility is impaired in chronic heart failure, many pharmacologic agents have been developed to increase the contractile state of the failing heart. These drugs produce impressive hemodynamic effects, but long-term therapy has to failed to produce clinical benefits and has increased mortality in treated patients. This experience has led many physicians to suggest that positive inotropic therapy be abandoned as a therapeutic approach for heart failure. However, recent studies suggest that the efficacy and safety of many (if not all) positive inotropic drugs can be greatly enhanced by reducing the dose of these drugs. The importance of dose is dramatically illustrated by the results of trials with vesnarinone, which decreases mortality when used in low doses but increases mortality when administered in doses only twice as large.Although low doses of positive inotropic drugs may be clinically superior to high doses, it is not clear that these low doses exert significant inotropic effects. All positive inotropic drugs exert actions on the circulation in addition to stimulating the heart, and these ancillary properties may be particularly important at low doses of these drugs. Low doses of milrinone and pimobendan may act primarily to dilate peripheral blood vessels; low doses of digitalis may exert only neurohormonal effects, and low doses of vesnarinone may act as an antiarrhythmic agent. If the noninotropic actions of low doses account for the therapeutic benefits of these drugs, then the positive inotropic effects seen at high doses may be primarily responsible for their adverse effects.Therefore, hemodynamic activity should not be viewed as a prerequisite for the selection of the dose of a positive inotropic drug. Prior emphasis on the use of high doses with significant cardiostimulatory effects may have derailed the proper development of many positive inotropic agents for the treatment of heart failure.

A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure.

We performed a prospective, randomized, double-blind, crossover study to compare the efficacy and safety of vasodilation with the calcium entry blocker nifedipine with that of isosorbide dinitrate (ISDN) and their combination as treatment for heart failure. Twenty-eight patients with New York Heart Association Functional class II or III chronic heart failure due to left ventricular systolic dysfunction were studied. All patients were maintained on a constant dose of digitalis and diuretics throughout the study. Eight weeks of therapy with nifedipine alone or in combination with ISDN resulted in a significantly higher incidence of heart failure deterioration necessitating hospitalizations and/or additional diuretics. Twenty-four percent of patients required hospitalization during nifedipine therapy and 26% required hospitalization during nifedipine-ISDN combination therapy in comparison to 0% requiring hospitalization during ISDN therapy alone. The total number of heart failure-worsening episodes was nine among patients on nifedipine, three among patients on ISDN (p less than 0.09 versus nifedipine), and 21 among patients on nifedipine-ISDN combination (p less than 0.001 versus nifedipine, p less than 0.0001 versus ISDN). Premature discontinuation of drug administration due to clinical deterioration or other side effects occurred in 29% of patients during nifedipine therapy, 5% of patients during ISDN therapy (p = 0.05 versus nifedipine), and 19% of patients during the combination therapy. A comparison of eight patients who demonstrated clinical deterioration on nifedipine with the remainder of the patients demonstrated no significant difference in left ventricular ejection fraction (0.24 +/- 0.06 versus 0.23 +/- 0.07) or maximal oxygen uptake during exercise (13 +/- 3 versus 14 +/- 2 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Multifocal Atrial Tachycardia

Abstract Multifocal atrial tachycardia was seen in 32 elderly and severely ill patients, with a high prevalence of acute and chronic pulmonary disease and cor pulmonale. Twelve patients (37.5 per cent) died. Bronchodilators were used frequently and contributed to the rapid heart rates. The arrhythmia itself was rarely due to digitalis intoxication. Serious arrhythmias did not arise in patients receiving maintenance doses of digitalis. Increments of digitalis often produced high-grade atrioventricular block, atrial tachycardia with block, nodal rhythms and ventricular irritability. Multifocal atrial tachycardia should be carefully distinguished from other atrial arrhythmias, especially atrial fibrillation. This is particularly important for rational digitalis therapy. Control of the arrhythmia paralleled improvement in ventilation and oxygenation, control of sepsis, correction of metabolic and electrolyte derangements and reduction in chronotropic drugs used as bronchodilators. The role of antiarrhythmic a...

Long-term follow-up of the f wave amplitude in chronic atrial fibrillation

Long-term follow-up of the amplitude of fibrillatory waves (f waves) on the standard electrocardiograms 0.6 +/- 3.3 yr, up to 20 yrs) was performed in 45 patients with chronic stable atrial fibrillation (24 men and 21 women, average age 60.2 +/- 11.5 yrs). The patients were divided into three groups on the basis of the underlying heart disease. Seventeen patients with mitral stenosis were classified as the MS group, 11 with hypertensive heart disease, old myocardial infarction, and aortic insufficiency as the HD group, and 17 without apparent heart diseases as the no heart disease (NHD) group. The f wave amplitude was measured at lead V1 according to the technique employed by Peter. The initial f wave amplitudes of the MS group (0.24 +/- 0.12 mV, mean +/- SD) and of the HD group (0.19 +/- 0.08 mV) were significantly larger than that of the NHD group (0.13 +/- 0.08 mV, p less than 0.05). The f wave amplitudes were significantly decreased during the observation period in each group, and the terminal f wave amplitudes (expressed as the percent of the initial f wave amplitude) were 61 +/- 34% in MS group, 59 +/- 26% in the HD group and 67 +/- 34% in the NHD group. In the NHD group, there was no significant difference in the terminal f wave amplitude between the cases with (n = 10) and without (n = 7) maintenance dose of digitalis. These results showed the apparent reduction of the f wave amplitude with perpetuation of this arrhythmia, and suggested that maintenance doses of digitalis had little effect on this process.