PubMed Health⌕ Search

Biomedical subjects

T B Levine

Publications and source records attributed to T B Levine.

At least 37 records · Page 2Linked to original sources
PubMed1996

Exercise training in patients with heart failure. A randomized, controlled trial.

OBJECTIVE: To assess the benefit of exercise training in patients with heart failure caused by left ventricular systolic dysfunction and to further describe the physiologic changes associated with exercise training in these patients. DESIGN: Randomized, controlled trial. SETTING: Urban outpatient clinic. PATIENTS: 40 men with compensated heart failure who were receiving standard medical therapy were randomly assigned to an exercise-training group or to a control group that did not exercise. Fifteen of the 21 patients assigned to exercise training and 14 of the 19 patients assigned to the control group completed the study. INTERVENTION: Patients assigned to exercise training participated in a program of three exercise sessions per week for 24 weeks. MEASUREMENTS: Symptom-limited exercise tests with gas exchange analysis done just before randomization, at week 12, and at week 24. RESULTS: At week 24, the following changes (mean +/- SE) were seen in patients in the exercise group and patients in the control group, respectively; exercise duration, 2.8 +/- 0.6 minutes and 0.5 +/- 0.5 minutes; peak oxygen consumption (VO2), 231 +/- 54 L/min and 58 +/- 38 L/min; peak ventilation, 12 +/- 3 L/min and -4 +/- 3 L/min; peak heart rate, 10 +/- 4 beats/min and -2 +/- 4 beats/min; and peak power output, 20 +/- 6 W and 2 +/- 5 W. Differences between the increases occurring in the exercise group and the changes occurring in the control group were significant (P < 0.05). Among patients in the exercise group, 85% of the increase in peak VO2 occurred by week 12, and 46% of the increase in peak VO2 was caused by the increase in peak heart rate. CONCLUSION: Exercise training does not appear to be contraindicated in patients with compensated heart failure. Exercise training improved exercise tolerance, as measured by increases in peak VO2, exercise duration, and power output. This improved exercise tolerance was caused in part by an increase in peak heart rate.

Adult↗
PubMed1996

Reinnervation of the transplanted human heart as evidenced from heart rate variability studies.

This study evaluated heart rate variability (HRV) after cardiac transplantation in humans in an attempt to test the hypothesis that cardiac reinnervation occurs in the post-transplant period. HRV was measured using 24-hour Holter recordings performed on 37 ambulant patients 1 to 122 months after cardiac transplantation. All patients were free of histologic rejection and were taking no medication likely to influence HRV. Time and frequency domain were analyzed and circadian rhythm of hourly average heart rate was calculated. HRV increased with time after the transplant. Compared with patients in the early post-transplant period, patients > 36 months after transplant had lower 24-hour heart rates (86 vs 93 beats/min), an increased average of all 5-minute SDs of NN intervals (17.6 vs 11.3), and higher low-and high-frequency power. Ten of the 27 patients > 3 years after transplantation had evidence of functional cardiac reinnervation. Compared with patients who had no reinnervation, these patients had increased circadian variability with lower nocturnal heart rates (76 vs 91 beats/min) and greater sympathetic activity during daytime (natural logarithm sympathetic power -0.36 vs -1.45) and nighttime (natural logarithm sympathetic power -0.43 vs -1.98). Despite lower nocturnal heart rates, there was no HRV evidence for an increase in parasympathetic activity. Thus, patients late after cardiac transplantation have HRV evidence for an increase in sympathetic control of the heart.

Adult↗
PubMed1996

Clinical status of patients removed from a transplant waiting list rivals that of transplant recipients at significant cost savings.

We retrospectively contrasted the medical outcome of patients removed from the heart transplant consideration list because of clinical improvement with that of transplant recipients. Of 60 patients awaiting transplantation, 18 were removed from the list (group A), and 42 required transplant or died (group B). Group A significantly improved regarding exercise oxygen uptake, ejection fraction, and hemodynamics. For more than 2 years after transplantation or "delisting," both groups had comparable symptoms (New York Heart Association class I to II) and cardiovascular mortality (1 of 18 for group A vs 3 of 32 for group B) but lower hospitalizations for group A (0.5 +/- 0.6 of 27 months per patient) versus group B (2.8 +/- 2.1 of 23 months per patient) (p = 0.0002). Despite two patients who had been removed from the list requiring transplantation, savings for delisting exceeded $2.2 million. Thus medical therapy allows transplant recipient list removal with clinical improvements sustained for 1 to 3 years at significant cost savings.

Cardiac Output, Low↗
PubMed1996

Effects of ACE inhibition and beta-blockade on skeletal muscle fiber types in dogs with moderate heart failure.

The proportion of slow-twitch, fatigue-resistant type 1 skeletal muscle (SM) fibers is often reduced in heart failure (HF), while the proportion of fatigue-sensitive type-II fibers increases. This maladaptation may be partially responsible for the exercise intolerance that characterize HF. In this study, we examined the effects of early monotherapy with the angiotensin-converting enzyme inhibor, enalapril, and the beta-blocker, metoprolol, on SM fiber type composition in 18 dogs with moderate HF produced by intracoronary microembolizations. HF dogs were randomized to 3 mo therapy with enalapril (10 mg twice daily), metoprolol (25 mg twice daily), or no treatment. Triceps muscle biopsies were obtained at baseline, before randomization, and at the end of 30 mo of therapy. Type I and type II SM fibers were differentiated by myofibrillar adenosinetriphosphatase (pH 9.4). In untreated dogs, the proportion of type I fibers was 27 +/- 1% before randomization and decreased to 23 +/- 1% (P < 0.05) at the end of 3 mo of follow up. In dogs treated with enalapril or metoprolol, the proportion of type I fibers was 30 +/- 4 and 28 +/- 2% before randomization and 33 +/- 4 and 33 +/- 1%, respectively, after 3 mo of therapy. In conclusion, in dogs with moderate HF, early therapy with enalapril or metoprolol prevents the progressive decline in the proportion of type I SM fibers.

Adrenergic beta-Antagonists↗
PubMed1996

Risk factors for early, cumulative, and fatal infections after heart transplantation: a multiinstitutional study.

BACKGROUND AND METHODS: By multivariable analysis, risk factors were identified for initial infection of any type, cumulative infections during the first 6 months and fatal infection among 2210 heart transplant recipients at 30 institutions. RESULTS AND CONCLUSIONS: Of the 1218 infections in 695 patients, bacterial infections were most frequent (47%), followed by viral (42%), fungal (8%), and protozoal (4%). Risk factors for earlier infection included older recipient age (p < 0.0001), ventilator support at time of transplant (p < 0.0001), ventricular assist device at time of transplant (p = 0.02), OKT3 induction therapy (p < 0.0001), donor black race (p = 0.0007), and positive donor cytomegalovirus serology (for cytomegalovirus infection) (p = 0.0007). Cumulative infections during the first 6 months were increased by older recipient age (p < 0.0001), ventilator support at transplant (p = 0.0004), ventricular assist at transplant (p = 0.009), Black donor (p = 0.03), female donor (p = 0.03), and OKT3 induction therapy (p = 0.005). The actuarial freedom from fatal infection was 96% at 1 year and 95% at 3 years. Risk factors for death from infection included very old (p = 0.002) and very young recipients (p = 0.004), ventilator support at time of transplant (p = 0.004), older donor (p < 0.0001), and longer donor ischemic time (p = 0.02). The risk of death from infection within the first 3 months exceeded 20% among older recipients (> 55 years) on ventilator support at time of transplantation who received an older (> 50 years) donor heart.

Actuarial Analysis↗
PubMed1996

Reversal of end-stage heart failure is predicted by long-term therapeutic response rather than initial hemodynamic and neurohormonal profile.

BACKGROUND: Long waiting list periods for heart transplantation have led to clinical improvements for some patients resulting in their removal from the waiting list. This study sought to determine what characteristics differentiated those patients with a good clinical outcome from those who continued to need a transplant. METHODS: The initial and final serial (every 3 months) right heart catheterization data of 60 patients awaiting transplantation were retrospectively analyzed, and the patients were divided into two groups: group A, patients who were taken off the list in follow-up because of improvement (n = 18 of 60), and group B who continued to require transplantation or died (n = 42 of 60). RESULTS: For Group A, there were significant declines in right atrial pressure (9 +/- 4 to 4 +/- 3 mm Hg, initial versus final, p = 0.001), systolic pulmonary arterial pressure (51 +/- 17 to 34 +/- 6 mm Hg, p = 0.0001), with an increase in electron in ejection fraction (20% +/- 4% to 34% +/- 10%, p = 0.005). The change in cardiac output and norepinephrine level was not statistically significant. For Group B, there were no changes in the initial and final values of right atrial pressure, systolic pulmonary arterial pressure, pulmonary capillary wedge pressure, or norepinephrine levels. A significant rise in ejection fraction from 17% +/- 22% +/- 8%, p = 0.003 did occur. The majority of patients in group A (12 of 18) had idiopathic dilated cardiomyopathy. In contrast, an ischemic etiology was found in the majority of group B patients (25 of 42). CONCLUSIONS: This study shows that transplant waiting list outcome cannot be predicted from a patient's initial hemodynamic or neurohormonal presentation. Rather, those patients capable of reversing their hemodynamic derangements with therapy over time are most likely to sustain a favorable clinical outcome. It appears that patients with idiopathic rather than ischemic cardiomyopathy respond more favorably to medical interventions with improved prognosis.

Adult↗
PubMed1994

Abnormalities of contractile structures in viable myocytes of the failing heart.

We examined the incidence and severity of abnormalities of contractile structures of residual viable cardiomyocytes in the left ventricular free wall, septum and right ventricular free wall of 10 dogs with chronic heart failure produced by multiple intracoronary microembolizations and in septal biopsies of 13 patients with chronic heart failure. The abnormalities were evaluated by transmission electron microscopy and classified as either (i) type-1, defined as complete interruption of myofibrils; (ii) type-2, defined as disconnection of end-sarcomeres from the intercalated disc; or (iii) type-3, sarcomere abnormalities defined as Z-bands irregularities and/or focal myofilament disarray. In the left ventricular free wall of dogs, type-1 abnormalities were present in 33 +/- 8% of myocytes, type-2 in 26 +/- 8%, and type-3 in 63 +/- 9%. The incidence of a type-3 abnormality but not type-1 or type-2 was greater in the left ventricular wall compared with the septum and right ventricular wall (P < 0.05). Among abnormal myocytes, 29 +/- 3% of myofibrils were interrupted, 18 +/- 4% of end-sarcomeres were disconnected from the intercalated disc and 12 +/- 2% of sarcomeres were abnormal. The severity of a type-1 but not type-2 or type-3 abnormalities was greater in the left ventricular wall compared with the septum and right ventricular wall. A similarly high incidence of abnormalities was observed in septal myocytes of patients. The results indicate that abnormalities of contractile structures are common among viable myocytes of the failing heart. The incidence of these abnormalities is sufficiently high to warrant serious consideration of their potential role in the progression of left ventricular dysfunction that characterizes the heart failure state.

Actin Cytoskeleton↗
PubMed1994

Cardiovascular responses of cardiac transplant patients to arm and leg exercise.

This investigation compares the cardiovascular responses of normal (n = 10) and cardiac transplant (n = 14) subjects to peak arm and leg exercise. It also tests the hypothesis that the higher heart rate (fc) in normal subjects during light (30 W) submaximal arm versus leg exercise is due to cardiac innervation. In cardiac transplant patients, power output, oxygen consumption (VO2), fc and rate pressure product were 54%, 28%, 7%, and 8% lower during peak arm than leg exercise, respectively. In normal subjects, power output, VO2, fc and rate pressure product were 61%, 33%, 8%, and 11% lower during peak arm than leg exercise, respectively. In cardiac transplant patients there was no significant difference in absolute fc during submaximal arm and leg exercise. In normal subjects, absolute fc during arm and leg exercise was [mean (SD)] 97 (4) beats.min-1 and 92 (4) beats.min-1, respectively (P = 0.07). Plasma noradrenaline was increased more during arm than leg exercise in both cardiac transplant and normal subjects. Maximal leg testing is useful when determining the capacity of cardiac transplant patients to perform arm work. The higher absolute fc reported by other investigators for normal subjects during submaximal arm versus leg exercise may be mediated by cardiac innervation.

Arm↗
PubMed1994

Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction.

BACKGROUND: Recent clinical trials have suggested that therapy with angiotensin-converting enzyme inhibitors in asymptomatic patients with reduced left ventricular (LV) function can significantly reduce the incidence of congestive heart failure compared with patients receiving placebo. In the present study, we examined the effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF). METHODS AND RESULTS: LV dysfunction was produced in 28 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after the last embolization, dogs were randomized to 3 months of oral therapy with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n = 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n = 7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/- 1%, P < .001) and LV end-systolic volume (ESV) and end-diastolic volume (EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/- 6 mL, P < .001, and 61 +/- 6 versus 78 +/- 8 mL, P < .002, respectively). In dogs treated with enalapril or metoprolol, LVEF remained unchanged or increased after therapy compared with before therapy (35 +/- 1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P < .05), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased significantly. CONCLUSIONS: In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfunction and LV chamber dilation. Therapy with digoxin maintains LV systolic function but does not prevent progressive LV enlargement.

Animals↗
PubMed1994

Exercise training in a patient with congestive heart failure on continuous dobutamine.

We present a 53-yr-old man with congestive heart failure who underwent 32 wk of exercise training. The patient was on a continuous infusion of dobutamine for 10 months prior to exercise training, which was subsequently discontinued at wk 24 of exercise training. Symptom-limited graded exercise tests were performed at baseline, wk 12, wk 24, and wk 32 of exercise training. While on a continuous infusion of dobutamine, the patient's oxygen consumption and exercise duration were increased during the exercise training period. Additionally, the patient was able to maintain these changes for 8 wk while continuing to exercise after the discontinuation of the dobutamine therapy.

Dobutamine↗
PubMed1994

Cardiovascular responses to submaximal arm and leg exercise in cardiac transplant patients.

We examined whether an increase in stroke volume (SV) contributes to the increase in cardiac output that occurs when cardiac transplant patients (CT) exercise between 50% and 75% of maximum. Upright arm and leg exercise was performed by 13 CT and 10 normal controls. Cardiac output (CO2 rebreathing), expired air, and catecholamine measures were obtained at rest and at 50% and 75% of maximum. From rest to 50% of maximum both normals and CT increased heart rate (HR) and SV during arm and leg exercise. In normals, HR (arm = +17 +/- 2 min-1; leg = +21 +/- 3 min-1) was increased further at 75% of maximum but not SV (arm = 3 +/- 4 ml; leg = +2 +/- 8 ml). In CT, further increases in both HR (arm = +9 +/- 1 min-1; leg = +13 +/- 1 min-1) and SV (arm = +12 +/- 5 ml; leg = +12 +/- 3 ml) were observed at 75% of maximum. During leg exercise plasma norepinephrine was increased more in CT than in normals. Between 50% and 75% of maximum, an increase in SV is a more important mechanism for increasing cardiac output during upright arm and leg exercise in CT than in normals.

Arm↗
PubMed1993

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

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

Animals↗
PubMed1993

Platelet function, thrombin and fibrinolytic activity in patients with heart failure.

Assays which detect the release of platelet-specific proteins and of peptides during thrombogenesis and are considered markers of activation of platelets and the coagulation system have recently been developed. This study was designed to utilize these haemostasis-related markers to test the hypothesis that a prethrombotic state is related to the presence, aetiology and severity of heart failure. Seventy patients with heart failure were evaluated and data were compared with 36 normal volunteers and 41 patients with coronary artery disease without heart failure (CAD). Thrombogenesis was documented using assays which measure platelet function, thrombin activity and fibrinolysis. Platelet function was measured by determining plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (BTG). Thrombin-antithrombin III complexes (TAT) and fibrinopeptide A (FPA) were determined to evaluate thrombin activity. Fibrinolytic activity was assessed by measuring D-Dimer levels. Patients with heart failure, when compared to normals, had increased plasma levels of BTG (89 +/- 62 IU.ml-1 vs 50 +/- 59 IU.ml-1, P < 0.01), TAT (4.6 +/- 4.3 micrograms.l-1 vs 2.3 +/- 0.64 micrograms.l-1, P < 0.005), and D-Dimer levels (506 +/- 444 IU.ml-1 vs 191 +/- 144 IU.ml-1, P < 0.0001). Patients with heart failure, when compared to the CAD group, had increased plasma levels of D-Dimer (506 +/- 444 ng.ml-1 vs 191 +/- 144 ng.ml-1, P < 0.05). Aetiology of heart failure did not affect these measurements. Patients with severe heart failure, as determined by high plasma norepinephrine concentration or low ejection fraction, were more likely to have activation of platelets and the coagulation system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Decreased proportion of type I myofibers in skeletal muscle of dogs with chronic heart failure.

BACKGROUND: Whether biochemical and histological abnormalities of skeletal muscle (SM) develop in patients with chronic heart failure (HF) remains controversial. In the present study, dogs with chronic HF were used to examine potential alterations of SM fiber type, fiber size, number of capillaries per fiber (C/F), beta-adrenergic receptor density (Bmax), and fiber ultrastructural integrity. METHODS AND RESULTS: HF was produced in 17 dogs by sequential intracoronary microembolizations. Biopsies of the lateral head of the triceps muscle were used in all studies. Type I and type II fibers were differentiated by myofibrillar ATPase (pH 9.4 or 4.2). Bmax was assessed by radioligand binding and SM ultrastructure by transmission electron microscopy. Comparisons were made with biopsies obtained from nine control dogs. The percentage of SM type I fibers was reduced in HF dogs compared with control dogs (19 +/- 2% versus 32 +/- 5%) (p < 0.001), whereas the percentage of SM type II fibers was increased (81 +/- 2% versus 68 +/- 5%) (p < 0.001). The change in fiber type composition was not associated with a preferential atrophy or hypertrophy of either fiber type. There was no difference in SM Bmax (198.9 +/- 14.3 versus 186.8 +/- 17.3 fmol/mg protein) or in C/F (5.37 +/- 0.26 versus 5.84 +/- 0.21) between HF dogs and control dogs. No ultrastructural abnormalities were present in SM fibers of HF dogs. CONCLUSIONS: In dogs with HF, there is a decrease in the relative composition of the slow-twitch type I SM fibers and an increase in fast-twitch type II fibers. The shift in fiber type composition is not associated with preferential atrophy of either fiber type or with a reduction in C/F, beta-adrenergic receptor density, or structural abnormalities of the myofibers.

Angiography↗
PubMed1993

Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure.

BACKGROUND: Losartan is a new specific angiotensin II receptor antagonist with no agonist properties that provides the opportunity to study the consequences of angiotensin II blockade. The objective of the present study was to evaluate the hemodynamic and neurohormonal response to losartan in patients with congestive heart failure. METHODS AND RESULTS: After baseline hemodynamic measurements using balloon-tipped pulmonary artery and radial arterial catheters, patients were randomized to receive a single dose of placebo or 5, 10, 25, 75, or 150 mg losartan in a double-blind, sequential fashion. Hemodynamic and neurohormonal parameters were then measured periodically for 24 hours. Losartan caused vasodilation in a dose-dependent manner. By the area-under-the-curve method, the reduction in the mean arterial pressure and systemic vascular resistance grew larger up to a dose of 25 mg, but the higher 75- and 150-mg doses did not produce additional vasodilation. In response to losartan, there were compensatory increases in both angiotensin II concentrations and in plasma renin activity, which were greatest at the highest doses. Aldosterone concentrations were significantly lowered with losartan. CONCLUSIONS: Blockade of the angiotensin II receptor with the antagonist losartan causes vasodilator and neurohormonal effects in patients with congestive heart failure. The lack of additional vasodilator response with doses of more than 25 mg suggests that neurohormonal activation might limit the efficacy of high dose of losartan.

Angiotensin II↗