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Biomedical subjects

M Gheorghiade

Publications and source records attributed to M Gheorghiade.

At least 73 records · Page 4Linked to original sources
PubMed1995

Abnormalities of skeletal muscle metabolism during nerve stimulation determined by 31P nuclear magnetic resonance spectroscopy in severe congestive heart failure.

These data confirm the presence of abnormal skeletal muscle metabolic function in patients with chronic heart failure. These changes are independent of patient compliance and central hemodynamic response to conventional exercise, and may explain, in part, the marked decrease in exercise tolerance often observed in patients with chronic severe heart failure. The etiology of these abnormalities of metabolic function and nutritive flow remains uncertain. TNS may prove useful in further elucidation of the peripheral metabolic consequences of chronic heart failure.

Acute Disease↗
PubMed1995

Acute hemodynamic effects of the prostacyclin analog 15AU81 in severe congestive heart failure.

This multicenter, open-label study provides the first assessment of the safety and acute hemodynamic effects of a short-term infusion of 15AU81, a chemically stable analog of prostacyclin, in patients with New York Heart Association class III or IV heart failure. Twelve patients underwent sequential dose escalation by increasing the rate of the infusion at 15-minute intervals until the drug was no longer tolerated. Patients then received a 90-minute infusion at their maximum tolerated dose. The infusion was then discontinued and the subjects were observed during a 90-minute washout segment. Serial hemodynamic measurements were made throughout the dose-ranging, maintenance, and washout segments. A significant decrease in systemic vascular resistance (1,935 +/- 774 vs 1,243 +/- 351 dynes.s.cm-5; p < 0.001) and pulmonary vascular resistance (395 +/- 335 vs 223 +/- 198 dynes.s.cm-5; p = 0.008) occurred from the infusion of vehicle to the maximum tolerated dose. During dose titration, there was a a significant increase in cardiac index (1.9 +/- 0.7 vs 2.6 +/- 0.6 liters/min/m2; p < 0.001) and a tendency for a mild reduction in pulmonary artery wedge pressure (18 +/- 7 vs 17 +/- 6; p = 0.055) for the 8 patients with values on vehicle and maximum tolerated dose. These hemodynamic changes persisted during the maintenance infusion and disappeared rapidly during the washout segment. The most common adverse event to limit dose-ranging was headache, which occurred at a mean maximum tolerated dose of 36 +/- 15 ng/kg/min. Administration of 15AU81 was associated with significant acute hemodynamic improvement in patients with severe heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group.

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.

Aged↗
PubMed1995

Is there a role for epoprostenol in the management of heart failure?

Prostacyclin (PGI2, epoprostenol), a pulmonary and systemic vasodilating agent, has recently undergone long-term intravenous administration trials in patients with severe congestive heart failure. As in many other agents that have beneficial acute hemodynamic profiles, its effects on mortality have been disappointing. However, the drug continues to have a role in the short-term management of patients with decompensated heart failure because of its short half-life, lack of medium-term toxicity compared to sodium nitroprusside, and lesser tendency toward development of tolerance than intravenous nitrates. There may also be therapeutic effects other than its influence on central hemodynamics; in particular, inhibition of platelet aggregation and thrombus formation in small vessels may be of value in the long-term management of patients with primary pulmonary hypertension. It is possible that, like other agents such as vesnarinone (OPC-8212), achieving beneficial long-term effects may require identification of an ideal dose range. The most effective therapeutic doses in long-term administration may not correlate with the most effective doses during short-term hemodynamic studies.

Epoprostenol↗
PubMed1995

Economic outcomes of withdrawal of digoxin therapy in adult patients with stable congestive heart failure.

OBJECTIVES: This study sought to analyze the health and economic outcomes of withdrawal of digoxin therapy among U.S. adult patients with stable congestive heart failure. BACKGROUND: New information regarding the outcomes of digoxin withdrawal has been provided by the Prospective Randomized Study of Ventricular Failure and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trials. We interpreted and extrapolated the results of these trials to describe implications on a national level. METHODS: We used a decision-analytic model to estimate the outcomes of two alternative strategies to 1) continue and 2) withdraw digoxin in patients with congestive heart failure with normal sinus rhythm, New York Heart Association functional class II or III and left ventricular ejection fraction < or = 35%. Epidemiologic assumptions were derived from published reports and expert opinion. Assumptions regarding the effectiveness of digoxin therapy were derived from the RADIANCE and PROVED digoxin withdrawal trials. Hospital and Medicare data were used for economic assumptions. Calculated outcomes included treatment failures, cases of digoxin toxicity and health care costs. RESULTS: The continuation of digoxin therapy in these patients with congestive heart failure nationally would avoid an estimated 185,000 clinic visits, 27,000 emergency visits and 137,000 hospital admissions for congestive heart failure. After accounting for an estimated 12,500 cases of digoxin toxicity, the net annual savings would be $406 million, with a 90% range of uncertainty of $106 to $822 million. One-way sensitivity analysis indicated that digoxin therapy is cost-saving when the assumed annual incidence of digoxin toxicity is < or = 33%. CONCLUSIONS: The continuation of digoxin therapy in patients with stable congestive heart failure should be strongly considered, because this strategy is likely to lead to both lower costs and greater health benefits on the basis of available information.

Adult↗
PubMed1995

Hospitalized congestive heart failure patients with preserved versus abnormal left ventricular systolic function: clinical characteristics and drug therapy.

PURPOSE: To compare clinical characteristics of and pharmacologic therapy for hospitalized patients with congestive heart failure (CHF) and left ventricular systolic dysfunction or normal left ventricular systolic function. PATIENTS AND METHODS: Medical records were reviewed for all patients discharged with a principal diagnosis of CHF from a university hospital and a community hospital between September 1, 1991 and August 31, 1992. Pertinent medical history items and prescribed drug therapies at discharge were recorded for each patient's first calendar year admission. Patients were categorized as having either normal left ventricular systolic function or systolic dysfunction based on the results of echocardiography and radionuclide angiography or contrast ventriculogram. RESULTS: Of 298 patients with CHF, 92 (31%) had normal left ventricular systolic function. Patients with normal systolic function were older, were more often women, were less likely to have a history of coronary artery disease, and were more likely to have a history of hypothyroidism than patients with systolic dysfunction. However, the prevalence of clinical characteristics overlapped considerably between the two groups. Among patients with systolic dysfunction, 79% were discharged on a therapeutic regimen of digoxin, 65% on an angiotensin-converting enzyme inhibitor, and 26% on either a beta-blocker or a calcium channel blocker. Among patients with normal systolic function, 50% were discharged on a regimen of a beta-blocker or a calcium channel blocker and 38% were discharged on digoxin. Twenty-six percent of patients with normal systolic function and without a history of atrial fibrillation were discharged on a digoxin regimen. CONCLUSION: Hospitalized CHF patients with normal left ventricular systolic function and those with diminished left ventricular systolic function share many clinical features. Since recommended drug therapy and prognosis differ, our data underscore the importance of diagnostic testing to assess left ventricular systolic function. Drug therapy for CHF patients provides a major challenge for quality-of-care improvement.

Aged↗
PubMed1994

Reassessment of digoxin and other low-dose positive inotropes in the treatment of chronic heart failure.

Digoxin and other low doses of drugs that have inotropic properties may have an important role to play in the therapy of patients with chronic heart failure. There is convincing evidence that digoxin is effective in relieving the signs and symptoms of heart failure due to systolic dysfunction. While earlier results with some of the other agents have been disappointing, recent data suggest that a reevaluation of these agents is necessary. There is now compelling evidence that lower doses of these agents may be clinically useful without necessarily having any significant hemodynamic effects. The recent experience with vesnarinone is especially promising in showing that therapy with these agents may improve survival in addition to improving clinical status. It is becoming recognized that hemodynamic activity should not necessarily be a prerequisite for clinical utility for those agents. The neuroendocrine and electrophysiologic effects of many of these agents, including digitalis, remain incompletely characterized and may play an important role in their therapeutic benefit. It appears that certain drugs that have inotropic properties may be effective only when their inotropic effects are not readily demonstrated. Further research into the appropriate mechanisms of action and proper dosing of these drugs may lead to a renewed interest in the use of positive inotropes for chronic heart failure.

Adrenergic beta-Agonists↗
PubMed1993

Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study.

BACKGROUND: Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is not clear whether the drug has a role when patients are receiving angiotensin-converting-enzyme inhibitors, as is often the case in current practice. METHODS: We studied 178 patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril). The patients were randomly assigned in a double-blind fashion either to continue receiving digoxin (85 patients) or to be switched to placebo (93 patients) for 12 weeks. Otherwise, their medical therapy for heart failure was not changed. RESULTS: Worsening heart failure necessitating withdrawal from the study developed in 23 patients switched to placebo, but in only 4 patients who continued to receive digoxin (P < 0.001). The relative risk of worsening heart failure in the placebo group as compared with the digoxin group was 5.9 (95 percent confidence interval, 2.1 to 17.2). All measures of functional capacity deteriorated in the patients receiving placebo as compared with those continuing to receive digoxin (P = 0.033 for maximal exercise tolerance, P = 0.01 for submaximal exercise endurance, and P = 0.019 for New York Heart Association class). In addition, the patients switched from digoxin to placebo had lower quality-of-life scores (P = 0.04), decreased ejection fractions (P = 0.001), and increases in heart rate (P = 0.001) and body weight (P < 0.001). CONCLUSIONS: These findings indicate that the withdrawal of digoxin carries considerable risks for patients with chronic heart failure and impaired systolic function who have remained clinically stable while receiving digoxin and angiotensin-converting-enzyme inhibitors.

Captopril↗
PubMed1993

Hemodynamic response of a canine model of chronic heart failure to intravenous dobutamine, nitroprusside, enalaprilat, and digoxin.

The hemodynamic effects of acute intravenous administration of nitroprusside, dobutamine, enalaprilat, and digoxin was investigated in a canine model of chronic heart failure (CHF) produced by multiple sequential intracoronary microembolizations. Dobutamine (4 micrograms/kg/min) increased cardiac output (2.4 +/- 0.1 vs. 4.0 +/- 0.4 l/min; p < .001) and LV ejection fraction (LVEF; 26 +/- 1 vs. 30 +/- 4%; p < .01), and decreased systemic vascular resistance (SVR; 3620 +/- 170 vs. 2470 +/- 190 dynes sec cm-5; p < .001). Nitroprusside (3 micrograms/kg/min) acted as a venodilator; it decreased pulmonary artery wedge pressure (16 +/- 1 vs. 13 +/- 1 mmHg; p < .01) and SVR (3730 +/- 440 vs. 3210 +/- 280 dynes sec cm-5; NS) but had no effect on cardiac output. Enalaprilat (1.875 mg) produced a significant increase of cardiac output (3.0 +/- 0.5 vs. 3.8 +/- 0.5 l/min; p < .001) and LVEF (22 +/- 1 vs. 30 +/- 1%; p < .01), and decreased SVR (3280 +/- 400 vs. 2450 +/- 250 dynes sec cm-5; p < .01). Intravenous digoxin at a cumulative dose of 0.75 mg increased LVEF (23 +/- 2 vs. 31 +/- 2%; p < .01) but had no effect on SVR. These data indicate that this canine model of CHF responds to acute pharmacologic intervention in a manner comparable to that seen in patients with CHF. Accordingly, this model may be a useful tool for the preclinical evaluation of new drugs targeted toward the treatment of CHF and for investigating the mechanisms of action of drugs currently used for the treatment of this disease state.

Animals↗
PubMed1993

Prognostic significance of electrocardiographic persistent ST depression in patients with their first myocardial infarction in the placebo arm of the Beta-Blocker Heart Attack Trial.

The prognostic significance of ST segment depression in patients with their first acute myocardial infarction was investigated in 1444 patients with an acute myocardial infarction, who were randomly assigned to the placebo arm of the Beta-Blocker Heart Attack Trial (BHAT). Patients were divided retrospectively into three groups based on the presence or absence of > or = 1 mm ST segment depression in two contiguous leads of a 12-lead electrocardiogram obtained during the first few days after admission and at the time of randomization, which occurred at 9.7 +/- 3.3 days after the index myocardial infarction. Group 1 included 392 patients with no ST segment depression, group 2 comprised 713 patients with transient ST segment depression in the first few days after admission or at the time of randomization, and group 3 included 339 patients with persistent ST segment depression in the first few days after admission and at the time of randomization. At a median follow-up of 26 months, the mortality rate was 4.9% in group 1, 7.6% in group 2, and 13.6% in group 3. When Cox regression was used to adjust for baseline differences in other variables, the differences between the three groups continued to be highly significant (p = 0.005; 95% confidence intervals [0.6 and 1.4]). We conclude that persistent and transient ST segment depression in patients with their first myocardial infarction are strong predictors of increased long-term mortality when compared to patients without ST segment depression. These findings should be taken into consideration when stratifying patients at risk in the post-myocardial infarction period.

Electrocardiography↗
PubMed1993

Assessment and treatment of diastolic dysfunction.

Congestive heart failure almost invariably includes a component of diastolic dysfunction, and in many patients impaired diastolic filling is the predominant functional abnormality. Failure of myocardial relaxation depends on abnormalities of calcium uptake as well as on the systolic and diastolic loads, the nonuniformity of load and the passive elastic characteristics of the ventricle. The availability of noninvasive diagnostic testing has led to an increasing interest in the study of diastolic function and its clinical implications. Recent echo-Doppler techniques (transesophageal pulmonary venous velocity recording, automatic endocardial borders detection, 3D cardiac reconstruction) demonstrated abnormal left ventricular filling patterns in patients with various cardiac disorders. It is possible that the diastolic abnormalities of heart failure may be a more appropriate target for new therapeutic interventions and several classes of pharmacologic agents may be effective in the management of diastolic dysfunction.

Diastole↗
PubMed1993

Nicardipine in heart failure: distinguishing its acute beneficial from its chronic effects.

Concern over negative inotropic effects has limited the use of calcium blockers in patients with congestive heart failure. Nicardipine, a second generation dihydropyridine calcium channel blocker, has demonstrated positive hemodynamic effects in short-term therapy in patients with congestive heart failure. Prolonged use of calcium channel blockers remains contraindicated in patients with congestive heart failure due to the potential for activation of the renin-angiotensin system. However, acute intravenous nicardipine administration has important clinical applications (as in the management of surgical hypertension or hypertensive emergencies). Nicardipine may be safely used for these indications even in the presence of congestive heart failure.

Acute Disease↗
PubMed1993

Epidemiology of atrial fibrillation in patients hospitalized in a large hospital.

The prevalence of atrial fibrillation varies widely depending on the population studied. To understand the incidence of atrial fibrillation and its significance in relation to other diseases, 3 years (1989 through 1991) of consecutive hospital discharges from the neurology and internal medicine services at Henry Ford Hospital were studied. Of the 26,964 patients who qualified for analysis, 1346 (5%) had atrial fibrillation as 1 of their 5 recorded discharge diagnoses. Comparing the group without atrial fibrillation to those with atrial fibrillation, there were 51% males in both groups (p = 0.88). African-Americans comprised 33% of the patients with atrial fibrillation and 50% of the patients without atrial fibrillation (p < 0.001). The average age of those with atrial fibrillation was 72 +/- 13 years, and 58 +/- 18 years for those without atrial fibrillation (p < 0.001). Length of hospital stay was 9.6 +/- 8.6 days with atrial fibrillation and 7.6 +/- 9.2 days for those without atrial fibrillation (p < 0.001). After adjusting for the effects of age, significant positive associations were noted in those patients with atrial fibrillation whose co-existing condition was either stroke, heart failure, myocardial infarction, hyperthyroidism, or mitral valve disease. There was also a significant negative relationship between hypertension and atrial fibrillation. The most common of the 5 discharge diagnoses observed in patients with atrial fibrillation was congestive heart failure (40%), followed by hypertension (23%) and ischemic heart disease (21%). The existence of a comorbid disease in patients with atrial fibrillation is important, as it can influence medical management and prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Acute hemodynamic effects of digitalis.

The available data suggest that acute administration of digoxin improves rest and exercise hemodynamics in patients in sinus rhythm or in atrial fibrillation who manifest a low cardiac output and increased left ventricular end-diastolic pressure that is due to systolic dysfunction. It appears that these acute beneficial effects are maintained during chronic digoxin therapy. The hemodynamic effects of digoxin in patients with isolated diastolic dysfunction and abnormal hemodynamics remain to be investigated.

Animals↗
PubMed1992

Acute hemodynamic effects of digoxin alone or in combination with other vasoactive agents in patients with congestive heart failure.

Although digitalis preparations have been in use for greater than 200 years, it is only within the last 2 decades that the central hemodynamic and neurohumoral effects occurring over several hours following intravenous administration of digoxin have been investigated in patients with congestive heart failure (CHF). Although digoxin has been shown to stimulate myocardial contractility in tissue preparations, its positive inotropic activity does not consistently translate into improvements in hemodynamic measurements in humans. Digoxin given intravenously results in increased cardiac index and decreased heart rate, left ventricular filling pressure, and right atrial pressure, as well as in acute attenuation of neurohumoral abnormalities, in patients with chronic CHF who have abnormal baseline hemodynamic measurements. Unlike other drugs with positive inotropic activity, however, digoxin does not influence hemodynamics in normal volunteers or in CHF patients in whom hemodynamics have been normalized with other therapies. These differing effects may be related to the drug's diverse peripheral vascular effects in CHF patients in whom vasodilation may occur in comparison with those that occur in normal subjects in whom the peripheral vasoconstrictor effects may prevent the inotropic effects of the drug from being translated into an increase in cardiac output. The hemodynamic effects of digoxin in patients with chronic CHF due primarily to diastolic dysfunction have not been fully investigated. Intravenous digoxin produces hemodynamic effects in patients with CHF associated with acute myocardial infarction, but these changes are small compared with those resulting from the administration of dobutamine. Digoxin does not appear to influence hemodynamic measurements in patients with right ventricular dysfunction unless concomitant left ventricular failure is present. In patients with chronic left ventricular dysfunction, the hemodynamic effects of intravenous digoxin and vasodilators are enhanced when these agents are given in combination.

Cardiotonic Agents↗
PubMed1992

Review of randomized trials of digoxin therapy in patients with chronic heart failure.

Although digitalis glycosides were introduced in the treatment of cardiac maladies greater than 200 years ago, controversy persists regarding the precise role of digoxin in any multidrug approach to the treatment of congestive heart failure (CHF). Despite its widespread use for more than 2 centuries, only recently have double-blind, randomized, placebo-controlled trials of digoxin therapy been conducted in patients with moderate CHF and sinus rhythm. These trials demonstrate that digoxin is superior to placebo in improving left ventricular (LV) ejection fraction, increasing exercise capacity, and preventing CHF worsening. Digoxin produces benefits similar to those seen with angiotensin converting enzyme (ACE) inhibitors with regard to clinical compensation and improvement in LV function. However, improved survival is demonstrated only in response to ACE inhibitors. The recently completed RADIANCE study addresses the value of combining digoxin with ACE inhibitor therapy in patients with mild-to-moderate CHF. Because increased mortality has been reported with the newer oral inotropic agents, it currently appears that digoxin is the only oral inotropic agent useful in clinical practice in the treatment of CHF. However, the effects of digoxin on mortality in patients with CHF remain unknown. In the large, double-blind, randomized trial conducted by the National Heart, Lung, and Blood Institute, the effects of digoxin on mortality in patients with CHF and already being treated with ACE inhibitors are currently being evaluated. Presently, based on the results of placebo-controlled studies, it appears that digoxin, alone or in combination with ACE inhibitors, is beneficial in patients with any signs or symptoms of CHF due to systolic LV dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗