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M Gheorghiade

Publications and source records attributed to M Gheorghiade.

At least 55 records · Page 3Linked to original sources
PubMed1998

Standards of laboratory practice: cardiac drug monitoring. National Academy of Clinical Biochemistry.

In this Standard of Laboratory Practice we recommend guidelines for therapeutic monitoring of cardiac drugs. Cardiac drugs are primarily used for treatment of angina, arrhythmias, and congestive heart failure. Digoxin, used in congestive heart failure, is widely prescribed and therapeutically monitored. Monitoring and use of antiarrhythmics such as disopyramide and lidocaine have been steadily declining. Immunoassay techniques are currently the most popular methods for measuring cardiac drugs. Several reasons make measurement of cardiac drugs in serum important: their narrow therapeutic index, similarity in clinical complications and presentation of under- and overmedicated patients, need for dosage adjustments, and confirmation of patient compliance. Monitoring may also be necessary in other circumstances, such as assessment of acetylator phenotypes. We present recommendations for measuring digoxin, quinidine, procainamide (and N-acetylprocainamide), lidocaine, and flecainide. We discuss guidelines for measuring unbound digoxin in the presence of an antidote (Fab fragments), for characterizing the impact of digoxin-like immunoreactive factor (DLIF) and other cross-reactants on immunoassays, and for moni-toring the unbound (free fraction) of drugs that bind to alpha1-acid glycoprotein. We also discuss logistic, clinical, hospital, and laboratory practice guidelines needed for implementation of a successful therapeutic drug monitoring service for cardiac drugs.

Angina Pectoris↗
PubMed1997

Pharmacotherapy for systolic dysfunction: a review of randomized clinical trials.

Chronic heart failure (HF) is a leading cause of morbidity and mortality in the United States, affecting >4 million people. The increasing prevalence of HF has placed an enormous burden on the US healthcare system. For many patients with cardiovascular disease, HF is the final common pathway. Treatment strategies for HF are aimed at preventing and delaying progression of the disease and ultimately improving survival. This article reviews recent clinical drug trials for HF, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin II antagonists, vasodilators, beta-adrenergic blockers, positive inotropic agents, calcium antagonists, and antiarrhythmics. The benefits and shortcomings of these agents and the study designs are discussed. For patients with left ventricular (LV) systolic dysfunction, ACE inhibitors are the only agents that consistently improved survival and decreased the rate of HF progression. It is likely that beta-adrenergic blockers have the same effect. The syndrome of HF is complex with both peripheral and cardiac factors contributing to disease progression. The addition of a diuretic and/or digoxin is often needed to prevent worsening heart failure. Although an angiotensin II antagonist may also be beneficial in the treatment of HF, further studies are needed to clarify their precise role in the management of this condition. Calcium anatagonists, antiarrhythmics excluding amiodarone, and positive inotropes other than digoxin do not appear to prevent progression of HF nor improve survival. The most common cause of HF in the United States is related to coronary artery disease. Reduction of cardiac risk factors, such as smoking cessation, lowering serum cholesterol with diet and a lipid lowering agent, and blood pressure control, is likely to prevent the development or progression of HF.

Adrenergic beta-Antagonists↗
PubMed1997

Systolic function, readmission rates, and survival among consecutively hospitalized patients with congestive heart failure.

We sought to describe the relation between left ventricular systolic function and rates of hospital readmission and survival among consecutively hospitalized patients with congestive heart failure. Medical records were reviewed for these patients at an academic medical center between Jan. 1, 1992, and Dec. 31, 1993. Left ventricular systolic function assessments performed within 6 months before discharge were used to classify left ventricular systolic function. Hospital readmission rates and survival through Dec. 31, 1994, were compared between patients with systolic dysfunction and those with preserved systolic function. Among 412 patients hospitalized with a primary diagnosis of congestive heart failure, 224 had undergone a left ventricular function assessment during the 6 months before hospital discharge. In-hospital mortality and readmission rates were higher among patients without a recent assessment of left ventricular systolic function. Of patients with systolic dysfunction, 55% versus 41% of patients with preserved systolic function were either readmitted or had an emergency room visit within 6 months after discharge (p = 0.06). At 27 months' follow-up, cumulative survival probabilities were 65% for patients with preserved systolic function, 65% for patients with systolic dysfunction, and 60% for patients without a left ventricular systolic function assessment (p = 0.24). Patients without a recent left ventricular systolic function assessment have significantly higher hospital readmission rates than patients with a recent systolic function assessment. Among hospitalized patients, mortality rates are comparable between patients with systolic dysfunction and those with preserved systolic function. However, patients with heart failure with systolic dysfunction may have higher readmission rates.

Aged↗
PubMed1997

A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST).

This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death.

Aged↗
PubMed1997

Heart failure between 1986 and 1994: temporal trends in drug-prescribing practices, hospital readmissions, and survival at an academic medical center.

Since 1987, publications in widely circulated medical journals have reported improved survival and lower hospital readmission rates when patients with heart failure and systolic dysfunction are treated with angiotensin-converting enzyme (ACE) inhibitors. We describe changes in ACE inhibitor use among patients hospitalized with heart failure between 1986 and 1993. Simultaneous trends in readmissions and survival rates are reported. Subjects were 612 consecutive patients hospitalized with a principal diagnosis of heart failure at an academic medical center during the period of Sept. 1, 1986, to Dec. 31, 1987 (interval I) or during the period Aug. 1, 1992, to Nov. 30, 1993 (interval II). Medical records were reviewed for 434 patients, consisting of all patients hospitalized with heart failure during interval II and a randomly selected 50% subset of patients hospitalized during interval I. Among 145 patients with systolic dysfunction whose medical records were reviewed, ACE inhibitor prescriptions significantly increased between interval I and interval II (43% vs 71%, p < 0.01, odds ratio 3.22, 95% confidence interval 1.62 to 6.42). Prescriptions of ACE inhibitors combined with digoxin and a diuretic also increased (37% vs 56%, p = 0.02, odds ratio 2.22, 95% confidence interval 1.14 to 4.32). Among all 612 patients, 6-month heart failure readmission rates increased from 13% to 21% (p = 0.02, odds ratio 1.79, 95% confidence interval 1.10 to 2.82). There was no significant change in survival rate between interval I and interval II, however, survival rate was marginally significantly improved among patients with systolic dysfunction. Our results suggest that drug-prescribing practices have significantly changed between 1986 and 1993. The absence of observed improvement in outcomes may result from changes in hospital admission criteria for heart failure.

Aged↗
PubMed1997

Patients with mild heart failure worsen during withdrawal from digoxin therapy.

OBJECTIVES: We investigated whether patients with mild heart failure due to left ventricular systolic dysfunction were at risk of worsening during digoxin withdrawal. BACKGROUND: Deterioration during digoxin withdrawal is often believed to be restricted to patients with moderate to severe clinical evidence of heart failure. To test this hypothesis, we studied the outcome of patients categorized by treatment assignment and a clinical signs and symptoms heart failure score in two rigorously designed clinical heart failure trials: the Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trial. METHODS: Potential differences in treatment failure, left ventricular ejection fraction and exercise capacity were evaluated in three groups of patients: those with mild heart failure (score < or = 2) who were withdrawn from digoxin (Dig WD Mild); those with moderate heart failure (score > 2) who were withdrawn from digoxin (Dig WD Moderate); and patients who continued receiving digoxin regardless of heart failure score (Dig Cont). RESULTS: Heart failure score at randomization did not predict outcome during follow-up in Dig Cont-group patients. Dig WD Mild-group patients were at increased risk of treatment failure and had deterioration of exercise capacity and left ventricular ejection fraction compared with that in Dig Cont-group patients (all p < 0.01). Patients in the Dig WD Moderate group were significantly more likely to experience treatment failure than patients in either the Dig WD Mild or Dig Cont group (both p < 0.05). CONCLUSIONS: Patients with systolic left ventricular dysfunction were at risk of clinical deterioration after digoxin withdrawal despite mild clinical evidence of congestive heart failure.

Aged↗
PubMed1997

Digoxin therapy in chronic heart failure.

Digitalis has been used for more than 250 years, but its role in the treatment of chronic heart failure has been intensively investigated only during the past two decades. Digoxin increases cardiac output both at rest and during exercise, alone or in combination with ACE inhibitors, and these hemodynamic effects are sustained during chronic therapy. A daily dose of digoxin that achieves a serum concentration of approximately 1.2 ng/ml is associated with a significant improvement in central hemodynamics, particularly in patients with impaired cardiac function despite pretreatment with diuretics and ACE inhibitors. Acute administration of digoxin in patients with chronic heart failure has an immediate sympathoinhibitory effect, and chronic therapy is associated with a sustained decrease in serum norepinephrine concentration. Discontinuation of digoxin in patients with chronic heart failure resulted in hemodynamic deterioration, which was reversed when the drug was readministered. Randomized withdrawal of digoxin in patients receiving only diuretics (PROVED study), or its withdrawal in patients receiving diuretics and ACE inhibitors (RADIANCE study), was associated with worsening of the clinical evidence of heart failure and a decrease in left ventricular systolic function in both studies. In the only large-scale, placebo-controlled mortality study reported thus for (DIG Trial), 7788 patients received standard drug treatment for chronic heart failure in addition to either digoxin or placebo. Digoxin had no impact on survival over the 37 months of follow-up, but the incidence of hospitalizations due to worsening heart failure was significantly reduced in patients receiving the drug compared with those receiving placebo.

Cardiac Output, Low↗
PubMed1997

Update on digoxin and other oral positive inotropic agents for chronic heart failure.

The benefit of digoxin in chronic heart failure has been debated fervently for decades. In the 1970s, the use of digoxin was challenged due to the high incidences of digitalis toxicity and the lack of data on the effects of digoxin in patients with chronic heart failure. In the 1980s, interest in digoxin was renewed after several trials with oral inotropic agents demonstrated increased mortality. Recently, several trials have studied the hemodynamic, neurohormonal, and clinical effects of digoxin, providing further insights into the possible mechanisms for its beneficial effects in patients with chronic heart failure. In an effort to find new pharmacologic therapies for the treatment of this patient population, studies of newer oral inotropic agents such as vesnarinone, pimobendan, and ibopamine have been disappointing. This paper reviews data published or presented in 1995 and 1996 examining the effects of digoxin and other oral inotropic agents in patients with chronic heart failure.

Cardiotonic Agents↗
PubMed1996

Pharmacologic therapies after myocardial infarction.

Despite the availability and use of effective methods for limiting infarct size with thrombolytic agents and primary angioplasty, patients experiencing a myocardial infarction (MI) are at increased risk for a second cardiac event in the post-MI period (e.g., reinfarction, heart failure, and sudden death). For this reason, postinfarction risk management is crucial. An extensive data base has firmly established the efficacy of beta blockers in reducing cardiovascular risk following acute MI. The full advantages of angiotensin-converting enzyme (ACE) inhibitors have only recently begun to emerge as the result of a growing understanding of the mechanisms of adverse outcomes following MI. The importance of lipid-lowering agents, in particular the "statins," should be considered in all post-MI patients, especially since recent studies have conclusively shown improved survival and reduced rates of MI and coronary artery bypass surgery in this population with this therapy. Aspirin is now considered a standard part of the early management of the acute infarct patient as well as for secondary prevention in post-MI patients. At present, chronic anticoagulation with warfarin should be reserved for selected patients. The nondihydropyridine calcium antagonists diltiazem and verapamil can be considered for post-MI use only in patients in whom beta blockers are contraindicated and who have preserved systolic function and/or those without clinical heart failure. In contrast, the dihydropyridine calcium antagonists, particularly nifedipine, have no role in secondary prevention. Although long-term benefits are minimal, nitrates continue to be useful in post-MI patients with residual ischemia (angina or silent ischemia), heart failure (systolic or diastolic), or postinfarction hypertension. Antiarrhythmic agents, except amiodarone, are relatively contraindicated in post-MI patients. Recent data show that vitamin E reduces the rate of nonfatal MI. Its role in cardiovascular death and overall mortality remains to be clarified. Despite their demonstrated value, agents used in secondary prevention generally appear to be underutilized. In addition, when pharmacologic therapies are administered for secondary prevention, they are often prescribed at lower doses than those tested and proved in trials. A greater appreciation for the efficacy and safety profiles of these agents could lead to more widespread use and more pronounced reductions in morbidity and mortality among post-MI patients.

Adrenergic beta-Antagonists↗
PubMed1996

Decline in the rate of hospital mortality from acute myocardial infarction: impact of changing management strategies.

This study examined the profile and management of acute myocardial infarction in patients hospitalized in the coronary care unit of Henry Ford Hospital to determine risk factors or treatments that best explained a decline in in-hospital mortality rates. During the 1980s and early 1990s, many therapeutic advances occurred in management of acute infarction. Overall and in-hospital mortality were observed also to decline, but little is known about the relation of newer treatments to clinical outcome. The study population consisted of 1798 patients with a confirmed diagnosis of myocardial infarction. Of these, 982 consecutive patients were hospitalized in the coronary care unit of Henry Ford Hospital from January 1981 through December 1984 and compared with the 816 consecutive patients hospitalized from January 1990 through October 1992. Data on baseline demographics, initial clinical features, in-hospital management, and in-hospital outcome were compared for the two groups. Logistic regression was used to define independent predictors of the improved outcome of the two groups. Demographic features of the earlier group were similar to those of the later cohort, with the exception of a greater incidence of diabetes and hypertension and a lesser incidence of angina and prior heart failure. The occurrence of non-Q wave infarction increased from 27% in the earlier to 39% in the later group, whereas the magnitude of peak creatine kinase elevation in serum was higher in the later group. Medical management differed significantly, with increased use of aspirin, thrombolytics, heparin, warfarin, nitrates, and beta-blockers and decreased use of antiarrhythmic agents, digoxin, and vasopressors in the later group. Coronary revascularization was performed during hospitalization in 6.4% of the earlier group of patients and 31.6% of the later group. In-hospital mortality was 14.7% in the earlier group and 7.4% in the later group. Multivariate logistic regression analysis showed that the difference in mortality between the two groups was best accounted for by increased use of beta-blockers, angioplasty, and thrombolytics, decreased incidence of cardiogenic shock and asystole, and decreased use of lidocaine. In conclusion, the presentation and in-hospital management of patients with acute myocardial infarction has changed from the early 1980s to the early 1990s. The improved hospital mortality rate may be associated with both the expanded use of effective therapies and a more favorable in-hospital course, although these are not mutually exclusive.

Cardiovascular Agents↗
PubMed1996

Mechanisms and management of heart failure due to diastolic dysfunction.

A significant subset of patients with chronic heart failure have preserved systolic function and their symptoms are attributable to left ventricular diastolic abnormalities. In the setting of diastolic heart failure, the cardiac chambers are nondilated and have normal contractility, but left ventricular filling is impaired. This impairment in diastolic filling is related to both abnormalities of the passive elastic properties of the ventricle and impaired active relaxation as a result of any of the following: myocardial ischemia, hypertrophy, reduced beta-adrenergic tone, or increases in myocardial connective tissue. Therapy of diastolic heart failure is aimed at preventing and reducing left ventricular hypertrophy, treating elevated blood pressure, and reducing left ventricular filling pressure without reducing cardiac output. This may be achieved by maintaining sinus rhythm, slowing heart rate, and treating ischemia. Although calcium-channel blockers, beta-blockers, angiotensin-converting enzyme inhibitors, diuretics, and nitrates may improve symptoms in patients with diastolic heart failure, there are few data to indicate that these agents have an important effect on prognosis. Further studies of patients with diastolic heart failure are needed to assess its prevalence, clinical characteristics, prognosis, and response to therapy.

Aging↗
PubMed1995

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.

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: 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.

Aldosterone↗