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Biomedical subjects

M Jessup

Publications and source records attributed to M Jessup.

At least 19 recordsLinked to original sources

Dynamic cardiomyoplasty: expectations and results.

BACKGROUND: Cardiac transplantation is an option for only a small minority of patients with severe, chronic congestive heart failure. Transformed skeletal muscle has the potential to provide a durable form of fatigue-resistant muscle power to assist the cardiovascular system. METHODS: Since the first dynamic cardiomyoplasty performed by Carpentier and colleagues in 1985, the techniques to make this operative procedure an effective assist to the failed myocardium have been refined. Much has been learned about optimum patient selection so that perioperative morbidity and mortality is minimized. The cardiomyostimulator developed by Medtronic has undergone several revisions, primarily so that the stimulation of the muscle wrap is adaptive to variations in cardiac performance, such as those that occur with arrhythmia or during exercise. RESULTS: A review of the data to date suggest a substantial number of patients who undergo the procedure experience an enhanced quality of life, and an alleviation of their heart failure symptoms. Details of patient selection underscore that cardiomyoplasty is not an alternative to transplant. Seriously compromised patients with low peak oxygen uptake and very low ejection fractions have the highest short term mortality. CONCLUSIONS: Dynamic cardiomyoplasty remains a promising surgical option for patients with moderately-severe congestive heart failure (i.e. NYHA Class III patients). The ongoing randomized trial comparing cardiomyoplasty to standard medical therapy is expected to provide more detailed information about the benefits of this procedure.

Cardiomyoplasty↗

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↗

Diagnosis and management of iron-induced heart disease in Cooley's anemia.

Patients with homozygous beta-thalassemia are chronically transfused and, if not assiduously chelated, are at risk for cardiac dysfunction. Available data suggest that even in optimally chelated patients, cardiac pathology is abnormal secondary to iron deposition, fibrosis, hypertrophy, and the structural effects of chronic anemia. Evidence of myopericarditis may also be found. Cardiac performance is usually only subtly affected, primarily with diastolic abnormalities not routinely detected on echocardiograms or nuclear scan. In poorly chelated patients, severe heart failure occurs and is easily predictable but invariably fatal, despite treatment with diuretics, vasodilators, inotropes, and antiarrhythmics. Based on successful prevention of heart failure with ACE inhibitors in other forms of cardiomyopathy, we suggest multicenter trials to explore methods to stabilize cardiac function in patients at risk for iron-induced heart disease. Long-term adverse effects of iron deposition, diastolic dysfunction, and abnormal hormone regulation need to be quantitated in patients reaching their third and fourth decades when the potential for ischemic cardiac disease could compound cardiac dysfunction.

Anemia, Hemolytic↗

Retrospective risk analysis for early heart-related death after cardiomyoplasty. The Worldwide Cardiomyoplasty Group.

BACKGROUND: Dynamic cardiomyoplasty is an evolving treatment for heart failure that uses an electrically stimulated latissimus dorsi muscle wrapped around the heart to improve cardiac function. Preoperative patient characteristics and deaths after cardiomyoplasty have been recorded during the past 5 years in a cumulative database representing worldwide experience of 42 medical centers. METHODS: Statistical models of hazards (monthly death rates) were used to identify risk factors for transiently increased risk of cardiovascular mortality within 2 months after cardiomyoplasty. RESULTS: Actuarial survival (n = 261) was 88%, 80%, and 76% at 1, 3, and 6 months after cardiomyoplasty, respectively. The peak hazard of 6% dying per month occurred during the first month after the surgical procedure. Lower ejection fraction, increased number of major coronary arteries with > or = 70% stenotic lesions, and lower chronotropic responses during exercise were independent risk factors for the transient increase in early cardiovascular mortality. Early risk of cardiovascular mortality was significantly reduced as centers gained experience with more than 3 patients. CONCLUSION: Early survival after cardiomyoplasty has improved with experience and might be reduced further by preoperative assessments that identify patients at highest risk.

Actuarial Analysis↗

Lisinopril versus placebo in the treatment of heart failure: the Lisinopril Heart Failure Study Group.

Lisinopril, a long-acting, angiotensin-converting enzyme inhibitor, was compared with placebo in a randomized, parallel, double-blind, 12-week study of 193 patients with heart failure. All patients were New York Heart Association Functional Class II, III, or IV and had remained symptomatic despite optimal dosing with digoxin and diuretics. After 12 weeks of therapy, the improvement in treadmill exercise duration was greater in the lisinopril group (113 seconds) compared with the placebo group (86 seconds). This improvement in exercise duration was particularly evident in patients with left ventricular ejection fractions less than 35% (lisinopril = 130 seconds; placebo = 94 seconds). In patients receiving lisinopril, the increase in exercise duration was accompanied by an improvement in quality of life as measured by the Yale Scale Dyspnea/Fatigue Index and in signs and symptoms of heart failure. In addition, the lisinopril group had a larger mean increase (3.7%) in left ventricular ejection fraction when compared with the placebo group (1.3%). Thus, lisinopril, administered once daily for 12 weeks, was well tolerated and efficacious in the treatment of heart failure when used concomitantly with diuretics and digoxin.

Aged↗

A multicenter, randomized, double-blind, placebo-controlled trial of pimobendan, a new cardiotonic and vasodilator agent, in patients with severe congestive heart failure.

Pimobendan, a new oral cardiotonic and vasodilator agent, increases myocardial contractile force through specific inhibition of phosphodiesterase type III and increased calcium sensitivity of the myocardial contractile elements. The effects of pimobendan on left ventricular performance and maximal exercise capacity were studied in a multicenter, randomized, double-blind, placebo-controlled trial involving 52 patients with severe congestive heart failure despite diuretics, digoxin, and angiotensin-converting enzyme inhibitors. The acute hemodynamic evaluation included three single doses of 2.5, 5.0, and 10.0 mg of oral pimobendan, which was subsequently administered at a daily dose of 5 or 10 mg for 4 weeks. Acute administration of pimobendan significantly increased the resting cardiac index and lowered pulmonary capillary wedge pressure in a dose-dependent manner, whereas heart rate and systemic arterial pressure were not substantially altered. Patients receiving pimobendan, 5 and 10 mg daily, had a significantly greater increase in maximal exercise duration than those receiving placebo, that is, 144 +/- 30 and 124 +/- 33 seconds versus 58 +/- 25 seconds (p = 0.05). Peak oxygen uptake increased by 1.7 +/- 0.8 and 2.2 +/- 1.3 ml/kg/min in patients receiving pimobendan at a daily dose of 5 and 10 mg, respectively, whereas it decreased by 0.1 +/- 0.6 ml/kg/min in patients receiving placebo (p = 0.06). Thus pimobendan acutely improves resting left ventricular performance and chronically increases exercise duration and peak oxygen uptake in patients with severe congestive heart failure concomitantly treated with digoxin, diuretics, and angiotensin-converting enzyme inhibitors.

Cardiotonic Agents↗

Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. The Pimobendan Multicenter Research Group.

BACKGROUND: This multicenter trial was conducted to determine the efficacy and safety of pimobendan, an inotropic agent with calcium-sensitizing properties and activity as a phosphodiesterase inhibitor, in patients with heart failure. METHODS AND RESULTS: One hundred ninety-eight ambulatory patients with symptoms of moderate to severe heart failure despite therapy with digitalis and diuretics with or without a single vasodilator were randomly assigned to receive either placebo (n = 49) or pimobendan (n = 149) in a double-blind fashion for 12 weeks. A dose range of pimobendan was used including 2.5 (n = 49), 5 (n = 51), or 10 mg/day (n = 49). One hundred fifty-eight (80%) patients were taking a converting enzyme inhibitor (CEI) and 28 (14%) patients were taking a non-CEI vasodilator. At end point, the 5-mg dose of pimobendan significantly increase exercise duration compared with placebo (121.6 +/- 19.1 seconds, p less than 0.001), whereas the 10-mg dose produced an increase of borderline significance (81.1 +/- 19.5 seconds, p = 0.05). Peak VO2 was significantly increased by 2.23 +/- 0.58 ml/kg/min in the 5-mg group (p less than 0.01 versus placebo). Furthermore, quality of life measured with the Minnesota Living With Heart Failure Questionnaire improved by 8.5 +/- 2.3 units in the 5-mg group compared with 1.3 +/- 2.2 units in the placebo group (p less than 0.01). There were a total of 23 all-cause hospitalizations in the placebo group, which was significantly greater compared with 33 in the three groups treated with pimobendan (p less than 0.01). There were no significant differences between the placebo and pimobendan groups with respect to changes in ejection fraction and plasma norepinephrine measured at baseline and at the completion of the 12-week study, proarrhythmic effect, or the number of patients with a significant adjustment in background therapy. Eleven patients died, including three (6%) on placebo and eight (5%) on pimobendan (p = NS). Among all adverse events, headache tended to be more common in the pimobendan groups compared with placebo, with the incidence increasing with dose (p less than 0.05). CONCLUSIONS: These data demonstrate that pimobendan significantly increases exercise duration, peak VO2, and quality of life in patients with heart failure. Pimobendan appears to be useful adjunctive therapy when added to digitalis, diuretics, and vasodilators.

Analysis of Variance↗

Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Lack of benefit compared with placebo. Enoximone Multicenter Trial Group.

A multicenter double-blind, randomized, placebo-controlled trial of oral enoximone, a phosphodiesterase inhibitor, was conducted in 102 outpatients (50 receiving enoximone and 52 receiving placebo) with moderate to moderately severe congestive heart failure. All were on a long-term regimen of digoxin and diuretics without vasodilators and converting enzyme inhibitors. Symptom score was obtained, and exercise testing was performed monthly for 4 months. There were no differences between groups in symptoms or exercise duration at the end of 4 months. A subgroup undergoing analysis of oxygen consumption with measurement of anaerobic threshold during exercise showed an increase (p less than 0.05) in anaerobic threshold at 1 month with enoximone. (2.7 +/- 0.8 ml O2/kg/min) compared with placebo (-0.8 +/- 1.2 ml O2/kg/min). This improvement was not sustained at 4 months (0.5 +/- 1.7 ml O2/kg/min with enoximone and 0.2 +/- 1.5 ml O2/kg/min with placebo). The dropout rate was significantly higher (p less than 0.02) with enoximone (46%) than with placebo (25%). Adverse effects other than death were slightly, but not significantly, higher with enoximone (32%) than with placebo (22%). During therapy, five deaths occurred in the enoximone group, and none occurred in the placebo group (p less than 0.05). Two deaths were sudden, two were from progressive congestive heart failure, and one was from acute myocardial infarction. With intention-to-treat analysis and inclusion of patients who were removed from therapy because of lack of study drug effect, 10 deaths occurred in the enoximone group, and three occurred in the placebo group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The treatment of perinatal addiction. Identification, intervention, and advocacy.

Women of reproductive age who use and abuse psychoactive drugs and alcohol present a special challenge to primary care physicians. There are compelling medical reasons for identifying and intervening with pregnant women who are addicted or have alcoholism. The teratogenicity of all drugs of abuse and alcohol, the risk of infection with the acquired immunodeficiency syndrome (AIDS), and the potential for full recovery of a pregnant woman from addiction are some of the reasons that identification and intervention in the problem are indicated. Whether encountered in the clinic setting or in private practice, chemically dependent pregnant or postpartum women are usually responsive to appropriate physician interventions that include a detailed and caring confrontation- and advocacy-oriented support. Complex legal and ethical issues surround perinatal addiction including the role of toxicologic screening, reports to child welfare services, issues in noncompliance, and interdisciplinary case management.

Female↗

Identification and management of potential heart transplant recipients.

Transplantation should be performed to improve the quality and duration of life in patients with end-stage cardiac disease. Symptoms, left ventricular ejection fraction, previous and present medications, and an exercise tolerance test serve as basic screening information to identify potential transplant candidates. Patients need to have a psychological, financial, and behavioral profile that will allow them to withstand the rigors of the entire transplantation process, and have no other medical problems that would jeopardize their survival following transplant surgery. Maintenance of the patient's status while awaiting a cardiac donor begins with patient education and a search into the causes of underlying ventricular dysfunction. Medications subsequently used include diuretic agents, vasodilators, digitalis, anticoagulants, antiarrhythmics, and possibly beta-blocker therapy. When standard measures fail, potent inotropes and even mechanical assist devices are sometimes necessary. Future donor heart allocations will require more rigid criteria for the selection of cardiac transplant candidates.

Adult↗