PubMed Health⌕ Search

Biomedical subjects

M J Likoff

Publications and source records attributed to M J Likoff.

18 recordsLinked to original sources
PubMed1987

Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy.

To determine which of the many clinical parameters routinely collected influence mortality in patients with congestive heart failure (CHF), 201 patients with idiopathic or ischemic dilated cardiomyopathy were prospectively followed for a 28-month study period. Mean age of the study group was 62 +/- 10 years, 60% had ischemic cardiomyopathy, and two-thirds were in New York Heart Association functional class II or III. Fifteen clinical variables were analyzed using a Cox proportional hazards model, while individual variables also were calculated for independent prognostic significance. There were 85 deaths, 26 (31%) of which were sudden cardiac deaths. Three characteristics at the study entry independently predicted an increased mortality risk: left ventricular ejection fraction, maximal oxygen uptake and ischemic cardiomyopathy. A Cox proportional hazards model showed that the combination of VO2max, S3 and the diagnosis of ischemic cardiomyopathy provided the best estimates of risk for an early death. Mortality for the low-risk group was only 5% at 6 months and 10% at 1 year. In contrast, in patients with an S3, ischemic cardiomyopathy and low maximal oxygen uptake, 6-month mortality was 24% and 36% at 1 year (p less than 0.001). Thus, these patients at high risk with left ventricular dysfunction associated with ischemic heart disease, a decreasing exercise tolerance and the development of an S3 should be strongly considered for an interventional trial with the aim of decreasing mortality.

Adult↗
PubMed1987

Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: a multicenter study.

Milrinone is a new bipyridine inotrope that has shown promise in initial clinical testing when administered intravenously or orally. The present multicenter study was designed to evaluate the clinical effectiveness and safety of sustained (48 hour) intravenous infusions of different doses of milrinone, as would be used clinically, in a controlled fashion using invasive hemodynamic monitoring. Entry was limited to adult patients with chronic heart failure of functional class III or IV, with a cardiac index less than or equal to 2.5 liters/min per m2 or a pulmonary capillary wedge pressure greater than or equal to 15 mm Hg, or both. After stable baseline hemodynamic recordings were obtained, milrinone was given as loading (microgram/kg per 10 min) and maintenance infusions (microgram/kg per min) to 189 patients in one of four loading/maintenance dosage regimens: 37.5/0.375 (low dose, n = 26), 50/0.50 (intermediate dose, n = 95), 75/0.75 (high dose, n = 15) and 50/0.25 (lowest dose, n = 53). The lowest dose was shown to be ineffective for maintenance therapy. Effective individual patient responses were defined as greater than or equal to 20% increase in cardiac index or decrease in pulmonary capillary wedge pressure, or both. During early therapy (less than or equal to 3 hour), 99% of patients showed an effective maximal response, and 90% an effective mean response. An effective mean response was observed during days 1 and 2 in 80% of patients, with a positive dose-response trend (69% response, low dose; 80%, intermediate dose; 93%, high dose; day 1). Each loading regimen was effective, with maximal mean response occurring at 15 minutes. Cardiac index initially increased by an average of 24 to 42% for all patients in the three groups, whereas pulmonary capillary wedge pressure decreased by 24 to 33%. Initial decreases in systemic vascular resistance averaged 15 to 31%. Initial changes in heart rate (+4 to +13%) and mean arterial pressure (-2 to -13%) were modest. Significant mean hemodynamic responses were maintained over the 48 hours. Increases in cardiac index for days 1 and 2 averaged 38 and 39% for those completing constant low dose drug, 34 and 37% for intermediate dose and 73 and 44% for high dose. Decreases in pulmonary capillary wedge pressure for all patients averaged 18 to 32% on days 1 and 2, with little dose response. Heart rate changes were modest and variable, averaging -9 to 9%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Pharmacokinetics and hemodynamics of amrinone in patients with chronic cardiac failure of diverse etiology.

The pharmacokinetics of amrinone and its relationship to ventricular function were assessed in 15 patients with chronic cardiac failure following the administration of a single 100 mg oral dose. Patients examined had Class II (1 patient), Class III (13 patients) and Class IV (1 patient) heart failure as characterized by the New York Heart Association classification. Blood samples were obtained following amrinone administration at selected times for 8 hours following the dose. Cardiac output was assessed serially for 5 hours following amrinone dosing. Mean (SD) peak plasma concentrations of amrinone (2.1 (1.1) mcg/ml) were obtained 0.5 to 2 hours after drug administration. The mean (SD) apparent oral clearance, apparent volume of distribution at steady state and half-life of amrinone were 0.23 (0.13) L/hr/kg, 1.2 (0.4) L/kg, and 4.8 (3.0) hr. Peak increases in cardiac index averaged 50% of baseline values and improvement was maintained at least 5 hours following amrinone dosing when compared to baseline cardiac index (p less than 0.05). Examination of the relationship between cardiac index corrected for baseline and amrinone plasma concentrations within individuals yielded strong and highly significant relationships (r greater than 0.90; p less than 0.025) in five patients, while in the remaining patients, either no relationship existed or insufficient data was available for analysis. When the data from all patients were pooled, a modest though significant relationship (r = 0.67; p less than 0.01) existed between cardiac index corrected for baseline and the post-absorptive, post-distributive amrinone plasma concentration. No difference in response to amrinone as a function of failure etiology or functional aerobic capacity was evident. Evaluation of the relationships between the mean improvement in cardiac index versus amrinone plasma concentration, as well as the time courses of these parameters indicate that the site of action of amrinone may be pharmacokinetically distinguishable from plasma and the tissues in instantaneous equilibrium with plasma.

Acetylation↗
PubMed1986

Comparison of acute hemodynamic response to dobutamine and intravenous MDL 17,043 (enoximone) in severe congestive heart failure secondary to ischemic cardiomyopathy or idiopathic dilated cardiomyopathy.

The acute hemodynamic response to intravenous dobutamine administration was compared with intravenous MDL 17,043 administration in 8 patients with severe, chronic congestive heart failure. Simultaneous radionuclide angiography was performed with gated equilibrium blood pool imaging to derive left ventricular volumes and ejection fraction during serial hemodynamic measurements. Six patients had an optimal dobutamine dose of 10 micrograms/kg/min; 2 others were compared at a dose of 7.5 micrograms/kg/min; comparisons with MDL 17,043 were after a 1.5-mg/kg bolus dose in all 8 patients. Dobutamine and MDL 17,043 caused significant and similar increases in cardiac index and stroke volume index. Dobutamine significantly increased heart rate and MDL 17,043 did not. MDL 17,043 significantly decreased pulmonary artery wedge, mean pulmonary artery and right atrial pressures; dobutamine did not. Dobutamine increased end-diastolic volume in 4 patients, with little concomitant decrease in wedge pressure; MDL 17,043 caused no change or a decrease in left ventricular end-diastolic volume in 5 patients, but consistently decreased wedge pressure in all. Thus, the left ventricular pressure-volume curve was displaced downward to a more favorable position after MDL 17,043 but not after dobutamine. In patients with chronic congestive heart failure, acute myocardial performance was more optimally influenced by MDL 17,043 than dobutamine administration.

Adult↗
PubMed1986

Prospective evaluation of ventricular arrhythmias using electrophysiologic techniques.

Electrophysiologic testing is known to be of value both diagnostically and in the evaluation of treatment modalities for patients with recurrent sustained ventricular tachycardia, out-of-hospital cardiac arrest, and syncope of unknown etiology. Attention is being focused on the possibility of identifying patients at high risk for such lethal ventricular arrhythmias in the hope that prophylactic therapy could prevent such arrhythmias from occurring. In this article, the authors discuss the potential role of electrophysiologic testing in this prospective identification and review the current data in the two groups of patients that have been studied extensively in this regard--post-myocardial infarction patients and patients with left ventricular dysfunction and congestive heart disease. The element of study artifact is also addressed.

Arrhythmias, Cardiac↗
PubMed1985

Milrinone in the treatment of chronic cardiac failure: a controlled trial.

This study examines the acute hemodynamic response to intravenous and oral milrinone in 12 patients with moderate to moderately severe heart failure. The patients received milrinone or placebo at random in an 8-week double-blind trial. Dosing level and schedule were determined by the hemodynamic results. Acute and chronic plasma samples for milrinone concentration were drawn from patients throughout the study. Milrinone was administered intravenously in successive doses of 25, 50, and 75 micrograms/kg. This resulted in a 16.5%, 12.5%, and 28.4% peak increase in cardiac index, with a concomitant 24%, 29%, and 38% decrease in pulmonary capillary wedge pressure. There were no significant relationships between any of the mean maximal hemodynamic values and milrinone plasma concentration. Six patients received milrinone and six patients received placebo; only five patients completed the blinded phase. There was no significant difference between the groups in exercise capacity, but the conditions of five of the six patients who received placebo deteriorated. In two of the patients who received milrinone the aerobic capacity improved greater than 2 cc/min/kg over baseline, and an additional two patients reported a marked subjective improvement. The results of this study indicate that oral milrinone in the management of patients with chronic cardiac failure would justify larger controlled studies.

Administration, Oral↗
PubMed1985

The pressure-flow response of the pulmonary circulation in patients with heart failure and pulmonary vascular disease.

Although it is well known that the pulmonary circulation is altered in patients with pulmonary arterial or venous hypertension, the resultant hemodynamic behavior has not been systematically studied. We undertook to do so in a group of patients with pulmonary hypertension of diverse etiology. We measured pulmonary arterial (PAP) and occlusive wedge pressures and cardiac output at rest (i.e., standing) and during progressive upright treadmill exercise in 51 patients. Forty-two had chronic, stable, cardiac failure secondary to ischemic, myopathic or valvular heart disease and were grouped according to whether their mean PAP was less than (normotensive) or greater than (hypertensive) 19 mm Hg, and nine had pulmonary vascular disease of diverse etiology and were considered separately. In the majority of patients, we found that irrespective of whether the hypertension was arterial or venous in origin or etiology: the mean PAP-flow relationship was linear; pulmonary capillary wedge pressure was greater than or equal to the average closure pressure of the pulmonary vascular bed and could therefore be used as the downstream pressure in calculating pulmonary vascular resistance; and pulmonary vascular resistance declined with exercise. Notable exceptions to the third observation were patients with valvular heart disease or a resting pulmonary vascular resistance greater than 800 dyne-sec-cm-5.

Blood Pressure↗
PubMed1984

Myocardial energetics and clinical response to the cardiotonic agent MDL 17043 in advanced heart failure.

Cardiotonic agents may prove useful in the long-term treatment of chronic heart failure provided myocardial efficiency is enhanced and clinical status is improved. Accordingly, the short-term hemodynamic and clinical response to the phosphodiesterase inhibitor, MDL 17043, was evaluated. Intravenous increments of 0.05 mg/kg (maximal total 3 mg/kg) were given to a peak cardiac output response in 13 patients with New York Heart Association functional class IV heart failure secondary to ischemic or myopathic disease. Significant (p less than 0.05) responses at peak effect (1.7 mg/kg) included an increase in cardiac output (3.5 to 4.6 liters/min) and heart rate (86 to 90 beats/min) and a decrease in pulmonary capillary wedge (25 to 17 mm Hg), mean arterial (85 to 78 mm Hg) and right atrial (10 to 7 mm Hg) pressures. Coronary sinus flow (measured in nine patients) increased (122 to 144 ml/min, p less than 0.01) as did myocardial oxygen uptake (14.1 to 15.1 ml/min, p less than 0.01), whereas myocardial extraction of oxygen (78 to 72%, p less than 0.01) and lactate (24 to 9%, p less than 0.01) decreased with three patients producing lactate at the time of their peak cardiac output response. Nine of the 12 patients given long-term oral therapy improved at least one functional class at 2 weeks. This improvement was sustained at 20 weeks in five patients. Thus, MDL 17043 acutely improves the function of the failing heart. However, the decrease in oxygen extraction occurring with increased myocardial oxygen uptake suggests that intracoronary shunting may occur along with an increase in oxygen demand and contribute to myocardial anaerobiosis in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Amrinone in the treatment of chronic cardiac failure.

The efficacy and safety of oral amrinone were examined in 17 patients with moderately severe to severe heart failure that was refractory to standard medical therapy and vasodilators. The short-term and 28 week response to open amrinone therapy was assessed first, followed by a placebo-controlled, double-blind withdrawal study of two 13 week stages in nine patients. Rest and exercise ventricular function were determined before and after 32 hours of amrinone; aerobic capacity was serially assessed. After 2 hours, 1.64 mg/kg amrinone produced a 40% (p less than 0.001) increase in cardiac output and a 32% (p less than 0.02) decrease in pulmonary wedge pressure without altering heart rate or blood pressure. The exercise cardiac index-wedge pressure curve obtained 32 hours after the first oral dose was significantly shifted (p less than 0.05) above control values. A sustained improvement in maximal oxygen uptake was noted during long-term open amrinone therapy. Subsequently, seven of the patients randomized to placebo therapy had a significant deterioration of symptoms or exercise tolerance, or both. After 4 weeks of readministration of amrinone, clinical stability was once again established and exercise tolerance was improved by Weeks 8 to 16. Adverse effects of thrombocytopenia (one patient) and hepatic dysfunction (one patient) attributable to amrinone were observed. It is concluded that amrinone is effective in the long-term treatment of chronic cardiac failure.

Aged↗
PubMed1984

Exercise testing in the evaluation of the patient with chronic cardiac failure.

A single progressive upright treadmill or upright bicycle exercise test may be used to safely evaluate the functional aerobic capacity of patients with chronic cardiac failure of varying severity and origin. The non-invasive monitoring or respiratory gas exchange and the determination of VO2 max and the anaerobic threshold may be used to objectively grade the severity of chronic cardiac failure and the heart's pumping reserve. The serial monitoring of these indices of exercise performance should prove useful in following the natural history of cardiac disease and in assessing the response to various therapeutic interventions.

Cardiac Output↗
PubMed1984

Exercise testing to evaluate patients with pulmonary vascular disease.

The maximal oxygen uptake and anaerobic threshold can be determined in patients with pulmonary vascular disease from noninvasive gas exchange measurements during progressive exercise. Maximal O2 utilization correlates directly with the maximal level of cardiac output and is inversely proportional to the pulmonary vascular resistance and the level of pulmonary arterial pressure. The accuracy of predicting the hemodynamic profile from noninvasive gas exchange measurements will obviously improve as more such patients are evaluated. Therefore, the determination of VO2 max has the potential of becoming a practical screening technique for detecting and predicting the severity of pulmonary vascular disease.

Adult↗
PubMed1984

Exercise testing in the evaluation of cardiopulmonary disease. A cardiologist's point of view.

The heart and lungs work in synchrony as a metabolic unit to transport the respiratory gases, O2 and CO2, between the atmosphere and the metabolizing tissues. This article reviews the physiologic behavior of the cardiopulmonary unit; in particular it focuses on the physiologic stress of exercise and the utility of monitoring respiratory gas exchange during exercise to assess the nature of cardiovascular disease and its severity.

Aerobiosis↗
PubMed1983

The right ventricle: physiologic and pathophysiologic considerations.

The right ventricle (RV) is responsible for accepting venous blood and propelling it to the lungs where it is oxygenated and its CO2 eliminated. Under normal conditions, at rest and during exercise, the pressure required by the RV to maintain the cardiac output (CO) is modest. The functional significance of the RV in sustaining circulatory homeostasis, therefore, appears to be minimal. However, whenever pulmonary vascular resistance (PVR) is elevated (e.g., left heart failure or pulmonary vascular disease) or whenever venous return is reduced (e.g., hypovolemia, increased pleural pressure), the necessity of this pulsatile pump is without question. As a muscular pump, the thin-walled RV is not unlike the left ventricle (LV) except that during diastole it is twice as distensible as the LV and during systole its stroke volume is twice as sensitive to the level of ejection pressure. However, under conditions of chronic pressure overload, the RV will hypertrophy and become capable of generating systemic levels of pressure. This is particularly necessary during physical activity in patients with pulmonary vascular disease. Thus, the RV is an integral component of the body's gas transport system and its contribution to sustaining circulatory homeostasis is without question.

Adult↗
PubMed1983

The cardiopulmonary unit. The body's gas transport system.

In recent years cardiologists and pulmonologists alike have taken a very narrow view of the heart and lungs. Each specialty has focused its respective attention on either the left ventricle or the alveoli. Ejection fraction and arterial O2 tension have become the order of the day. These narrowly focused viewpoints of the heart and lungs have distracted us from an equally compelling and more global perspective--the cardiopulmonary unit, in which the heart and lungs function as an integrated metabolic unit responsible for the body's gas transport and, as such, serving the metabolic needs of the tissues. A disease involving the cardiovascular or respiratory systems will disrupt the ability of the cardiopulmonary unit to deliver O2 to the tissues. In more subtle expressions of disease, this defect in O2 transport may require the heightened O2 requirements of exercising muscle to become apparent. The integration of the heart and lungs and the right and left sides of the heart is fostered by a variety of physiologic factors, including pleural and airway pressures, the pericardium, the interventricular septum and alignment of muscle fibers between the ventricles and septum, and the thoracic cage itself. Through its functional integration, the cardiopulmonary unit has been able to link the metabolizing cells to the atmosphere.

Airway Resistance↗
PubMed1981

Unstable angina pectoris of new onset: a prospective clinical and arteriographic study of 75 patients.

Seventy-five patients with unstable angina pectoris of new onset (defined as of less than 90 days' duration) were prospectively evaluated in terms of clinical and arteriographic findings. In all patients the angina was considered unstable in terms of ease of provocation of anginal attacks and frequency of occurrence of attacks. Sixty patients had significant obstruction of at least one coronary artery, whereas 15 had insignificant disease (less than 70 percent arterial narrowing) or normal coronary arteries. Thirty-one patients (52 percent) had single vessel coronary disease, 11 (18 percent) had double vessel disease and 9 (15 percent) had triple vessel disease; the remaining 9 (15 percent) had left main coronary artery disease, either alone or in association with other vessel involvement. Of the 31 patients with single vessel disease, 24 (77 percent) had stenosis of the left anterior descending artery. The patients with single vessel disease did not differ from the patients with multivessel involvement with respect to risk factors or clinical presentation. It is concluded that patients with unstable angina of new onset have an unusually large incidence of single vessel coronary artery disease predominantly involving the left anterior descending coronary artery. Thus, these patients constitute a unique subset of patients with angina pectoris.

Adult↗