Biomedical subjects

K F Adams

Publications and source records attributed to K F Adams.

At least 37 records · Page 2Linked to original sources

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 practice guidelines for heart failure.

Development of guidelines can be a difficult process; each organization or institution must establish the rules and criteria for including specific therapies and the level of complexity needed. Specific outcomes must be incorporated, including maintenance of comfort and functionality, freedom from hospitalization, and survival. In existing guidelines for the management of heart failure, angiotensin-converting enzyme (ACE) inhibitor therapy is clearly the gold standard. However, there is still a high mortality with ACE inhibitor therapy; the key may be choosing the right patients. Current guidelines reflect the uncertainty regarding digoxin before the Digitalis Investigation Group (DIG) trial; obviously, these guidelines should be revisited. Clinical practice guidelines for the management of heart failure need to be revised to include a better consensus on beta-blockade, the new data on digoxin, emerging data on angiotensin II receptor antagonists, and current thinking on anticoagulant therapy.

American Heart Association↗

PubMed1998

Angiotensin-converting enzyme inhibition and vascular remodeling in coronary artery disease.

New insights from basic laboratory studies and clinical trials have raised the intriguing possibility that the renin-angiotensin-kinin system may play a critical part in the pathophysiology of atherosclerosis. These studies suggest the possibility of an important new therapeutic role for ACE inhibitors: reduction in the risk of atherosclerosis and the complications of coronary artery disease. Ongoing large-scale trials will establish whether the findings from basic laboratory studies and clinical heart failure trials will apply to patients with ischemic heart disease irrespective of the presence or absence of left ventricular dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗

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

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

The AHCPR clinical practice guideline for heart failure revisited.

OBJECTIVE: To review the Agency for Health Care Policy and Research (AHCPR) clinical practice guideline for heart failure and comment on the guideline regarding pharmacotherapy from the perspective of the latest clinical trial data and the authors' clinical experience. DATA SOURCES: A MEDLINE search (1966 to June 1997) of English-language literature pertaining to the pharmacotherapy of heart failure was performed. Special emphasis was placed on literature published in the last 5 years. Additional literature was obtained from reference lists of key articles identified through the search. DATA SYNTHESIS: Pertinent clinical trials were reviewed and considered along with information from the authors' database of over 800 patients with heart failure. Evidence concerning the use of angiotensin-converting enzyme inhibitors at appropriate dosages in all New York Heart Association classes of heart failure and the inclusion of digoxin as part of triple therapy in all symptomatic patients with left ventricular systolic dysfunction are reviewed. Strategies to circumvent clinical problems that may limit the proper application of standard therapeutic agents are considered, and the possible future role of beta-blockers as the therapeutic agents in patients with heart failure is discussed. CONCLUSIONS: The AHCPR guideline provides the clinician with an excellent framework for treating the patient with heart failure. Building on the fundamentals of the guideline, the clinician can carefully apply current therapy at appropriate dosages and in the best combinations to individualize and thereby optimize pharmacologic therapy for this patient population.

Adrenergic beta-Antagonists↗

PubMed1996

Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators.

BACKGROUND: We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a "third-generation" beta -blocking agent with vasodilator properties, in chronic heart failure. METHODS AND RESULTS: Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive treatment with placebo, 6.25 mg BID carvedilol (low-dose group), 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction [EF] units in the low-, medium-, and high-dose carvedilol groups, respectively, compared with 2 EF units with placebo, P < .001 for linear dose response) and survival (respective crude mortality rates of 6.0%, 6.7%, and 1.1% with increasing doses of carvedilol compared with 15.5% in the placebo group, P < .001). When the three carvedilol groups were combined, the all-cause actuarial mortality risk was lowered by 73% in carvedilol-treated subjects (P < .001). Carvedilol also lowered the hospitalization rate (by 58% to 64%, P = .01) and was generally well tolerated. CONCLUSIONS: In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose-related reductions in mortality and hospitalization rate.

Adrenergic beta-Antagonists↗

PubMed1996

Relation between gender, etiology and survival in patients with symptomatic heart failure.

OBJECTIVES: This study investigated the relation between gender, etiology and survival in patients with symptomatic heart failure. BACKGROUND: Previous work provides conflicting results concerning the relation between gender, clinical characteristics and survival in patients with heart failure. METHODS: We examined the relation of these factors in 557 patients (380 men, 177 women) who had symptomatic heart failure, predominantly nonischemic in origin (68%) and typically associated with severe left ventricular dysfunction. RESULTS: Follow-up data were available in 99% of patients (mean follow-up period 2.4 years, range 1 day to 10 years) after study entry, and 201 patients reached the primary study end point of all-cause mortality. By life-table analysis, women were significantly less likely to reach this primary end point than men (p < 0.001). A significant association was found between female gender and better survival (p < 0.001), which depended on the primary etiology of heart failure (p = 0.008 for the gender-etiology interaction) but not on baseline ventricular function. Women survived longer than men when heart failure was due to nonischemic causes (men vs. women: relative risk [RR] 2.36, 95% confidence interval [CI] 1.59 to 3.51, p < 0.001). In contrast, outcome appeared similar when heart failure was due to ischemic heart disease (men vs. women: RR 0.85, 95% CI 0.45 to 1.61, p = 0.651). CONCLUSIONS: Women with heart failure due to nonischemic causes had significantly better survival than men with or without coronary disease as their primary cause of heart failure.

Adolescent↗

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

Torsemide: a pyridine-sulfonylurea loop diuretic.

OBJECTIVE: To review the clinical pharmacology of torsemide and to compare it with currently available loop diuretics, particularly furosemide. DATA SOURCES: An English-language MEDLINE search, 1985 to October 1994, was used to identify pertinent literature, including review articles. DATA EXTRACTION: Data from scientific literature were extracted, evaluated, and summarized for presentation. Pivotal and representative studies are discussed relating to the pharmacology, pharmacokinetics, and use of torsemide in patients with congestive heart failure, renal disease, hepatic disease, and hypertension. DATA SYNTHESIS: Torsemide is a loop diuretic of the pyridine-sulfonylurea class. The bioavailability of torsemide is approximately 80%, with little first-pass metabolism, and torsemide can be given without regard to meals. The serum concentration reaches its peak within 1 hour after oral administration and diuresis lasts approximately 6-8 hours. Torsemide is eliminated both hepatically (80%) and renally (20%) as unchanged drug with an elimination half-life of about 3.5 hours. Because of the high bioavailability, oral and intravenous doses are therapeutically equivalent. Torsemide, and other loop diuretics such as furosemide, are indicated for the treatment of edema associated with congestive heart failure, renal disease, and hepatic disease. They also are indicated for the treatment of hypertension alone or in combination with other antihypertensive agents. Depending on the indication, the recommended initial adult dosage of torsemide is between 5 and 20 mg once daily orally or intravenously. Special dosage adjustments in the elderly are not necessary. CONCLUSIONS: Torsemide is a loop diuretic similar to furosemide, with similar indications. Torsemide is characterized by good bioavailability and once-daily dosing and, compared with furosemide, provides generally equivalent therapeutic efficacy.

Clinical Trials as Topic↗

PubMed1995

Antiarrhythmic action of pharmacological administration of magnesium in heart failure: a critical review of new data.

Congestive heart failure is characterized by contractile dysfunction and frequent complex ventricular ectopy. Despite advances in therapy, mortality from heart failure is substantial, estimated at 10-80 percent per year, and sudden death is common. Magnesium is the second most common intracellular cation, strongly influences cardiac cell membrane function, and is an important catalyst of many enzymatic reactions in the myocyte. Epidemiological studies have implicated magnesium deficit in the genesis of sudden death. Patients with congestive heart failure are predisposed to magnesium deficit for many reasons, including neurohormonal activation, poor gastrointestinal absorption, and drug therapy. Hypomagnesaemia is common in these patients and has been linked to an increased frequency of complex ventricular ectopy. Several early, uncontrolled studies have suggested a beneficial effect of magnesium administration on ventricular arrhythmias in patients with congestive heart failure. Two recent randomized, double blind, placebo-controlled trials have shown that both intravenous and oral administration of magnesium chloride results in a significant reduction in the frequency and complexity of ventricular arrhythmias in patients with congestive heart failure. Magnesium administration is well tolerated and serious adverse effects are rare. The potential mechanisms of the antiarrhythmic action of magnesium and limitations of the available data are discussed. The evidence reviewed suggests that serum magnesium concentrations should be monitored and corrected in patients with congestive heart failure. Ventricular arrhythmias may respond to acute intravenous magnesium administration, which should be considered as early therapy. Further study is needed to define magnesium dose and the effect of concomitant potassium administration. A prospective clinical trial is warranted to determine the chronic effects of magnesium administration in patients with heart failure.

Absorption↗

PubMed1994

Effect of acute magnesium administration on the frequency of ventricular arrhythmia in patients with heart failure.

BACKGROUND: There is a high incidence of ventricular arrhythmia and sudden death in patients with heart failure. Unfortunately, currently available antiarrhythmic agents have only limited efficacy and may result in proarrhythmia and hemodynamic deterioration in these patients. METHODS AND RESULTS: We studied the acute effect of intravenous magnesium chloride on the frequency and severity of ventricular arrhythmia in 30 patients with symptomatic heart failure using a double-blind, placebo-controlled crossover design. The left ventricular ejection fraction was 23.0 +/- 8.0% (mean +/- SD). No patient had a history of symptomatic ventricular arrhythmia or was receiving antiarrhythmic agents, calcium channel antagonists, or beta-blockers. Patients were randomized to receive placebo (5% dextrose [D5W] in water alone) or magnesium chloride in D5W given as a bolus of 0.3 mEq/kg over 10 minutes followed by a maintenance infusion of 0.08 mEq/kg per hour for 24 hours. The magnesium concentrations 30 minutes and 24 hours after the bolus were 3.6 +/- 0.1 and 4.2 +/- 0.1 mg/dL, respectively. There was no significant change in serum potassium concentration during magnesium administration. Blinded analysis revealed that administration of intravenous magnesium chloride, compared with placebo, significantly decreased total ventricular ectopy per hour (mean +/- SEM, 70 +/- 26 versus 149 +/- 64, P < .001), couplets per day (23 +/- 11 versus 94 +/- 59, P = .007), and episodes of ventricular tachycardia per day (0.8 +/- 0.2 versus 2.6 +/- 1.0, P = .051). CONCLUSIONS: Intravenous magnesium chloride administration reduces the frequency of ventricular arrhythmia in patients with symptomatic heart failure.

Adult↗

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

Efficacy of phosphodiesterase inhibition with milrinone in combination with converting enzyme inhibitors in patients with heart failure. The Milrinone Multicenter Trials Investigators.

We describe the results of two placebo-controlled trials (MIL-1077 and MIL-1078) designed to evaluate the clinical efficacy of oral milrinone administered together with converting enzyme inhibitors to patients with congestive heart failure. Although these trials were terminated prematurely, they provide the only controlled data regarding the effect of oral milrinone on exercise capacity in patients receiving converting enzyme inhibitors. Of the 254 patients randomized, 140 completed one of the trials or reached an end point and are the basis of this report. In both trials, there was a clear trend for an increase in exercise capacity in the milrinone-treated patients (+26 +/- 8% vs. +5 +/- 7% in MIL-1077 and +11 +/- 5% vs. +2 +/- 4% in MIL-1078). Symptoms of congestive heart failure were decreased in one trial but not the other. Quality of life, as assessed by a questionnaire, was not effected in either trial. There was an increased incidence of adverse events in milrinone-treated patients. Adverse events related primarily to hypotension and vasodilation led to discontinuation of drug in 18 milrinone-treated patients vs. 1 placebo-treated patient. Milrinone had little or no proarrhythmic effect and cardiovascular deaths were distributed equally between the milrinone and placebo groups. These data suggest that when used in combination with a converting enzyme inhibitor, oral milrinone improves exercise capacity but is associated with a high incidence of adverse events that appear to be related to excessive vasodilation.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Interrelationships between left ventricular volume and output during exercise in healthy subjects.

To better characterize the relationship between left ventricular volume response and improved ventricular ejection and output during supine exercise in normal subjects, 36 healthy asymptomatic volunteers (age 39 +/- 17 yr) were studied with radionuclide ventriculography during recumbent bicycle ergometry. Relative changes in left ventricular end-diastolic and end-systolic volume were measured at rest and during exercise by a modification of the radionuclide counts-based method that accounted for variability in stress blood pool counts. A biphasic response was noted in left ventricular end-diastolic volume with an initial increase in early exercise (8.5 +/- 11% at 200 kpm/min and 11 +/- 12% at 300 kpm/min) followed by a progressive and significant decline at peak exercise (-3.3 +/- 18% at 547 +/- 140 kpm/min; P < 0.05). There was substantial variation in end-diastolic volume response at peak exercise in the group as a whole, which could be more closely related to changes in end-systolic volume (r = 0.84, P < 0.0001) than in heart rate (r = -0.57, P < 0.01) or age (r = 0.36, P < 0.05) of the study subjects. Despite the decline in ventricular filling, systolic function appeared to improve dramatically at peak exercise (change in left ventricular ejection fraction 15.5 +/- 6.4, P < 0.0001). Although not directly related to increasing systolic ejection, end-diastolic volume was directly related to the percent change in stroke volume at peak exercise among the study subjects (r = 0.88, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Propranolol therapy alters estimation of potential cardiovascular risk derived from submaximal postinfarction exercise testing.

We studied the effect of propranolol administration on risk assessment based on submaximal exercise testing performed early after myocardial infarction. A total of 70 patients with recent infarction underwent modified Bruce treadmill testing with simultaneous measurement of expired gases in the absence of antianginal agents including beta-antagonists. Among these, 31 patients who had at least one of the following abnormalities--ST depression greater than or equal to 1 mm (22 patients), chest pain (four patients), or treadmill time less than 360 seconds (12 patients)--were studied in a randomized double-blind fashion and received either placebo or 240 mg of propranolol/day. A total of 28 patients completed the randomized phase and were able to undergo repeat exercise testing an average of 3.4 +/- 1.8 days later. Randomized groups were equivalent at baseline except for a higher peak oxygen consumption and carbon dioxide production (p less than 0.05) in the propranolol compared with the placebo group; these differences were taken into account in statistical analyses of the study data. Resting heart rate (59 +/- 1.2 versus 82 +/- 4.2 beats/min) and peak heart rate x systolic blood pressure (14,208 +/- 496 versus 20,075 +/- 1,062) were both significantly less (p less than 0.01) after propranolol than after placebo. Eight of nine patients treated with placebo maintained ST depression greater than or equal to 1 mm from the initial to the randomized exercise test, compared with only 4 of 13 receiving propranolol (p less than 0.01). In those with continued ST depression, time to positivity was significantly longer in those receiving propranolol compared with those taking placebo (538 +/- 73 versus 318 +/- 44 seconds, p less than 0.05). In contrast, the peak ratio between carbon dioxide production and oxygen consumption was higher in those receiving propranolol compared with those receiving placebo (0.93 +/- 0.04 versus 0.81 +/- 0.03, p less than 0.05). We conclude that propranolol therapy reduces evidence of ischemia and changes traditional estimates of potential cardiac risk derived from submaximal postinfarction exercise testing.

Cardiovascular Diseases↗