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Biomedical subjects

M Gheorghiade

Publications and source records attributed to M Gheorghiade.

At least 37 records · Page 2Linked to original sources
PubMed1999

Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction.

BACKGROUND: This study was designed to investigate the tolerability, safety, and effect on left ventricular function of a new long-acting preparation of metoprolol, metoprolol succinate (CR/XL). METHODS AND RESULTS: Sixty patients were randomly assigned with a 2:1 ratio, drug versus placebo, administered with a gradually increasing dose of 12.5 to 150 mg of blinded medication during an 8-week period and continued for 6 months. The average peak dose achieved was 99 mg and 132 mg in the metoprolol succinate and placebo groups, respectively. The drug was well tolerated and there was no significant difference in drug withdrawals, New York Heart Association class, or quality of life assessment. The increase in left ventricular ejection fraction measure at baseline and 6 months measured by radioisotopic ventriculography was greater in the metoprolol succinate group (27. 5% to 36.3%) than in the placebo group (26% to 27.9%) (P <.015). Examination of serial Holter electrocardiographic recordings indicate that metoprolol succinate therapy was associated with a significant (P <.05) decrease in total ventricular ectopy at 8 weeks of therapy and a decrease in ventricular couplets and nonsustained ventricular tachycardia at 8 through 26 weeks of therapy. No changes were observed in plasma norepinephrine during therapy except a transitory significant (P <.05) increase in N terminal proatrial natriuretic factor at 8 weeks in the metoprolol succinate group. CONCLUSIONS: This study indicates that treatment with metoprolol succinate for a 6-month period is safe and well tolerated and is associated with an increase in left ventricular ejection fraction and a decrease in ventricular ectopic beats.

Double-Blind Method↗
PubMed1999

Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: insights from the Flolan International Randomized Survival Trial (FIRST).

OBJECTIVE: To evaluate clinical characteristics and outcomes of patients with advanced heart failure receiving intravenous continuous dobutamine in the FIRST Trial (Flolan International Randomized Survival Trial). METHODS: Four hundred seventy-one patients with class IIIb to IV heart failure who were enrolled in the FIRST trial were included. Eighty patients treated with dobutamine at FIRST randomization were compared with 391 patients not treated with dobutamine at randomization. The occurrence of worsening heart failure, need for vasoactive medications, resuscitated cardiac arrest, myocardial infarction, and total mortality were compared between the 2 groups. RESULTS: The dobutamine group had a higher occurrence of first event (85.3% vs 64. 5%; P =.0006) and a higher mortality rate (70.5% vs 37.1%; P =.0001) compared with the no dobutamine group. Intravenous continuous dobutamine was an independent risk factor for death after adjusting for baseline differences. CONCLUSIONS: Dobutamine use at the time of randomization was associated with a higher 6-month mortality rate. This effect persisted after adjustment for baseline differences. This analysis challenges the concept that continuous intravenous dobutamine is beneficial to advanced heart failure patients with respect to survival.

Aged↗
PubMed1999

Management of high-risk subsets in unstable angina.

This article focuses on the optimal treatment of postinfarction, refractory, or recurrent angina based on the results of recent clinical trials. Many of our recommendations hold true for the general management of unstable angina, but special considerations for the high-risk subsets are emphasized. Specifically, we discuss acute medical management and suggest that an early aggressive strategy that leads to early coronary angiography with the goal of revascularization when feasible best serves this subset. A special emphasis on the emerging role of glycoprotein IIb-IIIa antagonists is made because the important role of platelets in coronary thrombosis has dominated recent views on the pathophysiology of unstable angina.

Angina, Unstable↗
PubMed1999

Beta-blocker therapy in advanced heart failure: clinical characteristics and long-term outcomes.

AIMS: To evaluate the clinical characteristics and long-term outcomes of advanced heart failure patients (NYHA Class IIIb-IV) receiving beta-blocker therapy vs. those patients not receiving beta-blockers at randomization in the FIRST trial, a randomized, double-blind, placebo-controlled trial of epoprostenol vs. usual care in advanced heart failure. METHODS AND RESULTS: The patient population consisted of 471 patients enrolled in FIRST with Class IIIb-IV heart failure, left ventricular ejection fraction (LVEF) of <30%, advanced hemodynamic abnormalities, and standard pharmacologic treatment of ACE-inhibitor, diuretics, and/or digoxin. The study cohort consisted of 448 patients not receiving beta-blockers and 23 patients receiving beta-blockers at randomization for the FIRST trial. Patients in the beta-blocker group had decreased rates of any clinical event (P = 0.03), worsening heart failure (P = 0.001), and death or worsening heart failure (P = 0.0008) than patients not receiving beta-blockers. After adjusting for prognostically important variables, the favorable effect of beta-blockers on worsening heart failure (P = 0.02) and death or worsening heart failure (P = 0.02) persisted. CONCLUSION: Patients with advanced heart failure who receive beta-blocker therapy have a lower rate of hospitalization and are less likely to experience worsening heart failure or death at 6 months than patients who are not treated with beta-blockers. These observational data contribute to the growing body of data demonstrating a favorable effect of beta-blockers on clinical outcomes in heart failure.

Adrenergic beta-Antagonists↗
PubMed1999

Lower thrombolytic use for African Americans with myocardial infarction: an influence of clinical presentation?

BACKGROUND: After myocardial infarction, African Americans have been reported to undergo fewer catheterization and revascularization procedures than whites, but few studies have addressed racial variations in the delivery of thrombolytic therapy. METHODS: We conducted a retrospective analysis of data prospectively collected on consecutive patients admitted with acute myocardial infarction to the 16-bed coronary care unit of a large, urban teaching hospital. RESULTS: Over a 5-year period, 1948 consecutive patients were admitted with acute myocardial infarction to a single coronary care unit. Thrombolysis was administered to 19% of 1024 African Americans and 29% of 924 whites (P <.01). The initial diagnostic impression on admission was "definite" infarction less often in African Americans (30%) than in whites (43%, P <.001), a difference that appeared to largely account for the difference in thrombolytic administration in a multivariable model. Mortality adjusted for age and concomitant illnesses was similar in African Americans compared with whites (relative risk 1.0, 95% confidence interval 0.78 to 1.51). CONCLUSIONS: Much of the racial variation in thrombolytic administration could be accounted for by differences in clinical presentation, an issue that requires further study.

Black or African American↗
PubMed1998

Diastolic heart failure: standard Doppler approach and beyond.

Evidence of normal systolic left ventricular function has been reported in up to 30-40% of patients with clinical signs of congestive heart failure, suggesting that diastolic dysfunction is an important predictor of prognosis and mortality. Doppler echocardiography as a noninvasive diagnostic procedure is able to provide immediate and relevant information on functional and structural changes underlying the clinical syndrome of heart failure. Four distinct early filling/late diastole (E/A) ratio patterns (normal, delayed relaxation, pseudonormal, restrictive) can be discerned if viewed within the context of other available clinical information. These patterns evolve from one to another in a single individual, with changes in disease evolution, treatment, and loading condition. They represent a continuum from normal to severe diastolic dysfunction, showing progressively increasing left ventricular (LV) chamber stiffness and subsequently decreasing deceleration time. The combination of Doppler restrictive filling pattern and decreased deceleration time provides important information that helps to differentiate gradations of diastolic dysfunction and has been found to be a potent predictor of prognosis and mortality in various cardiac conditions. When clinical and transthoracic data alone are not sufficient in guiding therapy of congestive heart failure, transesophageal echocardiography can be used to assess most Doppler flows, especially pulmonary venous and left atrial (LA) appendage flows. The use of the multiplane transducer in multiple intermediate scan planes further improves the possibility of optimizing the Doppler incident angle and obtaining the best Doppler recordings of the left upper or right upper pulmonary venous flow. Whereas LV diastolic dysfunction is common in patients with congestive heart failure and appears to be an important predictor of prognosis, little information is available about right ventricular (RV) diastolic dysfunction. The role of RV function in congestive heart failure has probably been underestimated and it is possible that RV diastolic dysfunction assessment is equally important in the follow-up of heart failure patients. Recently, 2 novel echocardiographic technologies for the assessment of ventricular wall dynamics have been developed--color kinesis and tissue Doppler imaging. Both techniques have recently been shown to provide global as well as regional information on LV contraction and filling. Complementary use of both techniques may allow a more complete noninvasive assessment of global and regional systo-diastolic LV function.

Cardiac Output, Low↗
PubMed1998

Patterns of angiotensin-converting enzyme inhibitor prescriptions, educational interventions, and outcomes among hospitalized patients with heart failure.

BACKGROUND: Among hospitalized patients with heart failure, we describe characteristics associated with prescription of angiotensin-converting enzyme (ACE) inhibitors in the doses recommended by clinical practice guidelines. We also describe the impact of ACE inhibitor prescriptions, increases in ACE inhibitor dose, and nonpharmacologic educational interventions on readmission-free survival rates. HYPOTHESIS: We hypothesize that care by a cardiologist physician and higher mean arterial blood pressure on admission are associated with receipt of optimal ACE inhibitor doses. We hypothesize that receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are associated with superior readmission-free survival. METHODS: Between January 1, 1992, and December 31, 1993, medical records were reviewed for consecutively hospitalized patients with a principal diagnosis of heart failure at an academic medical center. Documented instructions and medications prescribed at discharge were abstracted. Deaths and readmissions through December 31, 1994, were identified with the National Death Index and the study institution's administrative data base, respectively. RESULTS: During 1992 and 1993, 387 patients were discharged alive from hospitalization for heart failure. Among patients discharged on enalapril or captopril, 18% received doses recommended by heart failure clinical practice guidelines. Patients discharged on a recommended ACE inhibitor dose were more likely to be African-American and had lower sodium levels and higher mean arterial pressures than patients discharged on lower ACE inhibitor doses. In survival analyses, an increase in ACE inhibitor dose was associated with improved readmission-free survival, independent of left ventricular systolic function type. Receipt of an ACE inhibitor at discharge was also associated with superior readmission-free survival, while nonpharmacologic educational instructions were not associated with improved outcomes. CONCLUSION: Interventions are needed to improve the frequency with which ACE inhibitors are prescribed at recommended doses to hospitalized patients with heart failure. We conclude that among these patients, receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are each associated with measurable effects on readmission-free survival, while provision of educational instructions as currently practiced is not associated with better outcomes.

Aged↗
PubMed1998

Effects of propanolol in patients entered in the Beta-Blocker Heart Attack Trial with their first myocardial infarction and persistent electrocardiographic ST-segment depression.

OBJECTIVE/BACKGROUND: It has been shown that patients with an acute myocardial infarction and persistent electrocardiographic ST-segment depression are at high risk for subsequent cardiac events. The purpose of this retrospective analysis was to examine the long-term effects of propranolol therapy in patients with their first acute myocardial infarction and persistent electrocardiographic ST-segment depression. METHODS: The outcomes of 2877 patients enrolled in the Beta-Blocker Heart Attack Trial (BHAT) with their first myocardial infarction (75% of patients in BHAT) were reviewed. Patients were divided into three groups on the basis of presence or absence of > or =1 mm ST-segment depression in two contiguous leads of the 12-lead electrocardiogram obtained soon after admission or at the time of randomization, which occurred 10.1+/-3.5 days after the index myocardial infarction. Group 1 included 774 patients (392 randomly assigned to placebo and 382 to propranolol) with no ST-segment depression; group 2 included 1447 patients (713 placebo, 734 propranolol) with ST-segment depression at admission or at the time of randomization (labeled as transient); and group 3 included 656 patients (339 placebo and 317 propranolol) who had electrocardiographic ST-segment depression from the time of admission to the time of randomization (labeled as persistent). RESULTS: In group 3, patients with persistent electrocardiographic ST depression, the mortality rate in patients randomly assigned to placebo was 13.6% compared with 7.6% in patients with propranolol (p = 0.012; log rank test). Sudden death in the placebo arm was 9.7% compared with 4.7% in the propranolol group (p = 0.012, log rank test). The results of the Cox regression analysis, adjusting for all baseline variables with p values <0.25, showed the relative risk of overall mortality rate and the relative risk of sudden death were 2.13 ( 1.22, 3.70) and 2.56 (1.27, 5.26), respectively, for the placebo group compared with the propranolol group. Patients with persistent ST-segment depression had the greatest benefit from propranolol (47.2 fewer events [deaths/reinfarctions] per 1000 person-years compared with 78 and 2.1 fewer events in patients with transient and no ST-segment depression, respectively). CONCLUSIONS: It appears that the greatest benefit for beta-blocker therapy in patients after myocardial infarction is observed in patients with persistent ST-segment depression who are at greatest risk for death and reinfarction. Definitive conclusions regarding therapy with beta-adrenergic blocking agents in patients with persistent ST-segment depression cannot be made because our analysis, given its retrospective nature, is only hypothesis generating.

Adrenergic beta-Antagonists↗
PubMed1998

Clinical predictors of worsening heart failure during withdrawal from digoxin therapy.

Previous work provides limited information concerning predictors of clinical deterioration after digoxin withdrawal. We investigated the association between selected baseline clinical characteristics and symptomatic deterioration in two similarly designed trials: Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Cox proportional-hazards analysis found the following independent predictors of worsening during follow-up in the combined PROVED and RADIANCE patients: heart failure score, left ventricular ejection fraction, cardiothoracic ratio, use of an angiotensin-converting enzyme inhibitor, use of digoxin, and age. When these factors, except for digoxin use, were tested in the subgroup of patients withdrawn from digoxin, they all were significant independent predictors of worsening heart failure. In contrast, only use of angiotensin-converting enzyme inhibitor predicted deterioration in patients who continued digoxin. Patients with more congestive symptoms, worse ventricular function, greater cardiac enlargement, or who were not taking an angiotensin-converting enzyme inhibitor were significantly more likely to worsen early after digoxin discontinuation than patients without these characteristics.

Aged↗
PubMed1998

Superiority of "triple" drug therapy in heart failure: insights from the PROVED and RADIANCE trials. Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin. Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme.

OBJECTIVES: We sought to study the efficacy of "triple" therapy with digoxin, diuretic and angiotensin-converting enzyme inhibitor (ACEI) compared to other combinations of these drugs in patients with symptomatic left ventricular systolic dysfunction. BACKGROUND: Controversy continues concerning the role of combining digoxin with diuretic and ACEI in the initial management of patients with heart failure. METHODS: The study utilized data from two studies of digoxin efficacy: Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Worsening heart failure defined as augmentation of heart failure therapy or an emergency room visit or hospitalization for increased heart failure was the main outcome measure. RESULTS: A total of 266 patients comprising the four treatment groups of the combined PROVED (diuretic alone or digoxin and diuretic) and RADIANCE (ACEI and diuretic, or digoxin, diuretic and ACEI) trials were analyzed. Worsening heart failure occurred in only 4 of the 85 patients who continued digoxin, diuretic and ACEI therapy (4.7%) compared to 18 of the 42 patients (19%) on digoxin and diuretic therapy (p=0.009), to 23 of the 93 patients (25%) on ACEI and diuretic therapy (p=0.001) and to 18 of the 46 patients (39%) on diuretic alone (p < 0.001). Life table and multivariate analysis also demonstrated that worsening heart failure was least likely in patients treated with triple therapy (p < 0.01 vs. all other groups). CONCLUSION: Pending definitive, prospective clinical trials, our results argue for triple therapy as the initial management of patients with symptomatic heart failure due to systolic dysfunction.

Adult↗
PubMed1998

Clinical and neurohormonal effects of nicardipine hydrochloride in patients with severe chronic heart failure receiving angiotensin-converting enzyme inhibitor therapy.

It has been proposed that worsening of heart failure with dihydropyridines, such as nicardipine, is related to the activation of the neuroendocrine system. To test this, we evaluated 20 patients with severe heart failure (mean age, 55 +/- 13 years; New York Heart Association functional class III; left ventricular ejection fraction, 18% +/- 8% on maintenance therapy with captopril, digoxin, and diuretics) who were randomized to nicardipine (60 or 90 mg/d) or placebo during a 4-month double-blind protocol. The following measurements were obtained at baseline, monthly, and at 4 months or last follow-up visit: rest and exercise radionuclide ventriculography, maximal treadmill time, 6-minute walking test distance, serum norepinephrine and aldosterone concentrations, and plasma renin activity. During the follow-up period, worsening of heart failure occurred in 6 patients in the nicardipine group and in 2 patients in the placebo group (p = 0.06). The maximal treadmill time for a 6-minute walking distance and exercise radionuclide ejection fraction at the last follow-up visit did not change in patients who did not deteriorate with heart failure in the placebo or nicardipine groups as compared with baseline values. In this study group of patients with severe heart failure receiving therapy with digoxin, captopril, and diuretics, nicardipine was associated with worsening heart failure without an apparent activation of the neurohormones. However, because of the small number of patients and a significant number of patients who deteriorated during the follow-up period, no definitive conclusions can be made.

Aged↗