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Biomedical subjects

B Frey

Publications and source records attributed to B Frey.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comprehensive critical incident monitoring in a neonatal-pediatric intensive care unit: experience with the system approach.

OBJECTIVE: To examine the occurrence of critical incidents (CIs) in order to improve quality of care. DESIGN: Prospective survey. SETTING: Multidisciplinary, neonatal-pediatric intensive care unit (ICU) of a non-university, teaching children's hospital. PATIENTS: Four hundred and sixty-seven admissions over a 1-year period. METHODS: A CI is any event which could have reduced, or did reduce, the safety margin for the patient. Comprehensive, anonymous, non-punitive CI monitoring was undertaken. CI severity with respect to actual patient harm was graded: major (score 3), moderate (2) or minor (1). The system approach incorporates the philosophy that errors are evidence of deficiencies in systems, not in people. We undertook 2-monthly analyses of CIs. RESULTS: There were 211 CI reports: 30 % major, 25 % moderate, 45 % minor. The CI categories were management/environment 29 %, drugs 29 %, procedures 18 %, respiration 14 %, equipment dysfunction 7 %, nosocomial infections 3 %. The respiratory CIs were the most severe, the drug-related CIs the least severe (score mean, SD: 2.9, 0.26 vs 1.4, 0.76; p < 0.001). However, 20 out of 62 drug-related CIs were potentially life-threatening. Thirteen percent of drug CIs were decimal point errors. Eleven of the 29 respiratory CIs were accidental extubations (2.6/100 ventilator days). CIs were most often precipitated by consultants (32 %), followed by residents (23 %, over-represented in drug CIs, 22/62) and specialized nurses (21 %). Doctors had a greater proportion of major CIs than nurses (p < 0.01). Fifty percent of the CIs were detected by routine checks. The most important method of detection was patient inspection (44 %), alarms accounted for only 10 %. Contributing factors were human errors (63 %), communication failure (14 %), organizational problems (10 %), equipment dysfunction (7 %) and milieu (3 %). CONCLUSIONS: CIs are very common in pediatric intensive care. Knowledge of them is a precious source for quality improvement through changes in the system.

Child↗
PubMed2000

Experience with beta-blocker therapy in patients with advanced heart failure evaluated for HTx.

BACKGROUND: The aim of this study was to review our experience with beta-blocker therapy on top of high-dose angiotensin-converting enzyme inhibitors (ACE-I) in patients with advanced heart failure evaluated for heart transplantation, and to question the value of intended heart transplantation for patients receiving this therapy. METHODS: Three hundred eighteen patients (New York Heart Association (NYHA) function class III 34%, class IV 66%, average left ventricular ejection fraction (LVEF) 16%, and average cardiac index 2.2 l/min per m(2) at time of referral) were treated with digitalis, loop diuretics, maximally uptitrated ACE-I, beta-blockers (if tolerated), and intravenous support (if needed). After 3 months, patients were retrospectively stratified into those receiving beta-blockers plus ACE-I (Group A, n = 126), ACE-I (Group B, n = 135), and ACE-I plus intravenous support (Group C, n = 57). Endpoint 1 of the study was combined urgent heart transplantation, mechanical assist device implantation, and pretransplant death during a follow-up of 12 to 48 (mean 19 +/- 11) months. Endpoint 2 was posttransplant mortality up to 48 (mean 14 +/- 8) months. RESULTS: In the pretransplantation period the survival rate was 58% and the mortality rate was 20%. Between Groups A and B there was a significant difference in mortality (9% vs 27%, p = 0.001) due to a lower sudden-death rate in Group A (6% vs 17%, p < 0.01). While between Groups A and C all event rates of Endpoint 1 differed significantly, between Group C and Group B total mortality (30% vs 27%) was similar. However, in Group C urgent heart transplantation (HTx) was more often performed than in Group B (54% vs 11%, p < 0.0001). Seventy of 318 patients (22%) underwent heart transplantation (16% urgent, 6% elective). Posttransplant actuarial survival of the entire transplanted cohort (n = 70, 12 deaths) was significantly lower (log rank p < 0.01) than event-free survival in Group A (n = 126, 18 events), significantly higher (log rank p < 0. 0001) than event-free survival in Group C (n = 57, 34 events), and similar to that in Group B (n = 135, 52 events). CONCLUSION: This experience suggests that it may be particularly useful to add a beta-blocker to ACE-I therapy in patients referred for heart transplantation. In patients who tolerate this treatment, heart transplantation does not seem to provide additional survival benefit in the short term (2 years).

Actuarial Analysis↗
PubMed2000

ACE inhibitor dosage at the time of listing predicts survival.

BACKGROUND: To be listed for heart transplantation (HTx), optimization of the dosage of angiotensin converting enzyme (ACE) -inhibitors is recommended worldwide even though this issue has not been thoroughly investigated in the pre-transplantation cohort. OBJECTIVE: The aim of this database study was to analyze the prognostic impact of a pre-defined high vs a low ACE inhibitor dose range at the time of listing for elective HTx in addition to various previously established prognostic factors. METHODS: Medical records from 237 patients (84% male, mean age 54 years) admitted between January 1995 and January 1998 from 25 different centers in Austria were reviewed. Forty-seven percent were taking > or =75 mg captopril, > or =20 mg enalapril, > or =20 mg lisinopril or > or =5 mg ramipril daily ("high-dose" group) and 53% received smaller doses ("low-dose" group). RESULTS: No significant differences between groups were detected at baseline except that patients with higher ACE inhibitor doses were more likely to take nitrates, beta-blockers and amiodarone, received higher furosemide doses and had higher serum gamma-glutamyl transferase levels. Follow-up was 328 days (248 SD) with 16% deaths in the "high-dose" group vs 288 days (270 SD) with 25% deaths in the "low-dose" group. Kaplan-Meier survival curves demonstrated a significant difference over time between the two treatment groups (P = 0.03). Furthermore, dichotomized ACE inhibitor treatment at the time of listing was the strongest independent single predictor of mortality (P = 0.01) with only blood pressure (P = 0.02), alanine transaminase (P = 0.02) and left ventricular end diastolic diameter (P = 0.02) providing additional prognostic information. To explain these findings several factors have to be considered a) greater benefit with higher ACE inhibitor doses b) sicker patients receiving lower ACE inhibitor doses and c) more experienced heart failure care of the "high-dose" group. CONCLUSIONS: Heart transplantation candidates who, for whatever reason, receive ACE-inhibitors below the recommended dosages, are at increased mortality risk and thus merit greater scrutiny.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Effect of beta 1 blockade with atenolol on progression of heart failure in patients pretreated with high-dose enalapril.

BACKGROUND: The survival benefit of beta-blocker treatment in patients with heart failure has been established in recent trials. Yet, the impact of beta-blockers added on high dose angiotensin converting enzyme inhibitors has not been reported. AIMS: To investigate the effect of atenolol, a hydrophilic, selective beta1-adrenergic antagonist, added on enalapril 40 mg/day in patients with advanced left ventricular dysfunction in a double-blind placebo-controlled trial. METHODS: One hundred and nineteen patients with class II or III heart failure, left ventricular ejection fraction < or = 25% and treatment with 40 mg enalapril daily were given an initial challenge dose of atenolol 12. 5 mg. One hundred patients (54 with idiopathic, 28 with ischemic, 18 with other dilated cardiomyopathy) tolerated challenge and were randomized to atenolol (maintenance dose 89+/-11 mg/day, range 50-100 mg/day) or placebo. The primary endpoint was combined worsening heart failure or death within 2 years, the secondary endpoint was hospitalization for cardiac events. RESULTS: After 395+/-266 days interim analysis revealed a significant difference between the atenolol and placebo group (log rank P<0.01) and the trial was concluded. Twenty-seven patients had developed worsening heart failure (8 in the atenolol group vs. 19 in the placebo group) and 13 patients had died (5 in the atenolol vs. 8 in the placebo group). Overall there were 23 hospitalizations for cardiac events (6 in the atenolol group vs. 21 in the placebo group, P=0.07); 17 hospitalizations were due to worsening heart failure (5 in the atenolol group, 12 in the placebo-group, P=0.05) and 10 due to arrhythmias (1 in the atenolol group vs. 9 in the placebo group, P<0.01) CONCLUSIONS: The data suggest that in patients with advanced left ventricular dysfunction, beta-blockers can provide substantial benefits supplementary to that already achieved with high dose enalapril treatment.

Adrenergic beta-Antagonists↗
PubMed2000

Domain exchange: chimeras of Thermus aquaticus DNA polymerase, Escherichia coli DNA polymerase I and Thermotoga neapolitana DNA polymerase.

The intervening domain of the thermostable Thermus aquaticus DNA polymerase (TAQ: polymerase), which has no catalytic activity, has been exchanged for the 3'-5' exonuclease domain of the homologous mesophile Escherichia coli DNA polymerase I (E.coli pol I) and the homologous thermostable Thermotoga neapolitana DNA polymerase (TNE: polymerase). Three chimeric DNA polymerases have been constructed using the three-dimensional (3D) structure of the Klenow fragment of the E.coli pol I and 3D models of the intervening and polymerase domains of the TAQ: polymerase and the TNE: polymerase: chimera TaqEc1 (exchange of residues 292-423 from TAQ: polymerase for residues 327-519 of E.coli pol I), chimera TaqTne1 (exchange of residues 292-423 of TAQ: polymerase for residues 295-485 of TNE: polymerase) and chimera TaqTne2 (exchange of residues 292-448 of TAQ: polymerase for residues 295-510 of TNE: polymerase). The chimera TaqEc1 showed characteristics from both parental polymerases at an intermediate temperature of 50 degrees C: high polymerase activity, processivity, 3'-5' exonuclease activity and proof-reading function. In comparison, the chimeras TaqTne1 and TaqTne2 showed no significant 3'-5' exonuclease activity and no proof-reading function. The chimera TaqTne1 showed an optimum temperature at 60 degrees C, decreased polymerase activity compared with the TAQ: polymerase and reduced processivity. The chimera TaqTne2 showed high polymerase activity at 72 degrees C, processivity and less reduced thermostability compared with the chimera TaqTne1.

Amino Acid Sequence↗
PubMed2000

Heparin induces release of phospholipase A(2) into the splanchnic circulation.

UNLABELLED: Cardiopulmonary bypass results in increased plasma activity of phospholipase A(2) (PLA(2)) that appears to be caused by the administration of heparin. High PLA(2) activity may be responsible for increased production of eicosanoids and, thus, may be implicated in various pathophysiologic events associated with cardiac surgery. To investigate the site of PLA(2) secretion, blood samples were simultaneously collected from the radial artery, the pulmonary artery, and the hepatic vein at 2, 4, 6, and 20 min after systemic heparinization (350 U/kg). Within 2 min of the heparin injection, plasma activity of PLA(2) increased 4- to 9-fold and remained so for at least 20 min. Two minutes after the heparin injection, PLA(2) was significantly higher in the hepatic vein than in the radial artery (P: < 0.01). No such difference was detected between pulmonary and radial arteries. When heparin was added to blood samples in vitro (5-100 U/mL), plasma activity of PLA(2) did not increase, which suggests that the enzyme was not secreted by blood cells. IMPLICATIONS: Heparin, given in the dosage required for cardiopulmonary bypass, caused release of phospholipase A(2) into the splanchnic circulation.

Aged↗
PubMed2000

Tube feeding in nursing home residents with severe and irreversible cognitive impairment.

OBJECTIVES: This study was undertaken to determine the degree to which selected demographic and clinical variables are associated with the use of feeding tubes in older nursing home residents with very severe and irreversible cognitive impairment. DESIGN: Descriptive, cross-sectional, population-based study. SETTING: Kansas nursing homes from January 1, 1994, through June 30, 1998. PARTICIPANTS: A total of 4,997 nursing home residents with very severe and irreversible cognitive impairment comprised the study population. Subjects were identified using data in Minimum Data Set (MDS) reports. Those who were included in the study population were over the age of 65, had two consecutive Cognitive Performance Scale scores of 6, were without evidence of significant subsequent improvement, and were not comatose. MEASUREMENTS: The MDS data on each resident were examined to determine subjects' age, ethnicity, gender, Medicaid eligibility, disease diagnoses, physical functioning, and oral/nutritional status, including feeding tube status. The MDS was also used to determine urban versus rural location of the nursing home. The association between the use of feeding tubes and selected demographic and clinical characteristics was then examined using bivariate and logistic regression tests. RESULTS: Of the 4,997 residents in the study population, 577 (11.6%) had feeding tubes. In multivariate analysis, feeding tube use was found to be associated with swallowing problems (odds ratio (OR) 5.4, 95% confidence interval (CI) 4.3-6.8); urban location of nursing home (OR 2.9, 95% CI 2.3-3.5); non-white race (OR 2.7, 95% CI 1.9-3.6); stroke (OR 2.5, 95% CI 2.0-3.1); and absence of dementia (OR 2.5, 95% CI 2.0-3.1). Feeding tubes were also more weakly associated with age <86 years, male gender, dependency for all activities of daily living, and absence of a living will. Feeding tube use was not found to be associated with chewing problems, Medicaid status, or resuscitation status. CONCLUSIONS: Clinical variables including swallowing problems, stroke, and absence of dementia were strongly associated with the use of feeding tubes in this cross-sectional, population-based study. In addition, urban location of nursing home and non-white race were significantly associated with feeding tubes. These findings suggest that feeding tube decisions are strongly influenced by nonclinical factors and invite further investigation.

Activities of Daily Living↗
PubMed2000

Successful treatment of idiopathic left ventricular outflow tract tachycardia by catheter ablation or minimally invasive surgical cryoablation.

Idiopathic right ventricular outflow tract tachycardia is readily amenable to radiofrequency catheter ablation. However, treatment modalities for left ventricular outflow tract tachycardia are not well defined. Out of 37 patients with idiopathic outflow tract tachycardia referred for catheter ablation, in 3 patients tachycardia originated from the left ventricular outflow tract. On the surface ECG, all left ventricular tachycardias exhibited an inferior axis with a predominant negative QRS complex in lead I. Heart rate during tachycardia ranged from 115 to 170 beats/min. During electrophysiological testing, 1 patient had inducible tachycardia on orciprenaline challenge, 1 patient had inducible tachycardia at baseline, and 1 patient had incessant tachycardia. In two patients, earliest ventricular activation was recorded from the endocardial left ventricular outflow tract at an anterolateral and an anterior site, respectively. A distinct high frequency spike preceded the QRS onset by 66/78 ms. Application of radiofrequency energy successfully eliminated tachycardia at these sites. In one patient, tachycardia originated from the epicardial left ventricular outflow tract. Mapping of the anterior interventricular vein revealed a fractionated low amplitude signal occurring 46 ms before QRS onset. After failure of catheter ablation from the corresponding endocardial site, successful minimally invasive surgical focal cryoablation of the epicardial target region was performed. During a follow-up period ranging from 7 to 12 months, all patients remained free of tachycardia. In conclusion, ventricular tachycardia arising from the left ventricular outflow tract may require endo- and epicardial mapping. Successful treatment is achieved by radiofrequency catheter ablation or minimally invasive surgical cryoablation.

Adult↗
PubMed2000

Prognostic value of hemodynamic vs big endothelin measurements during long-term IV therapy in advanced heart failure patients.

STUDY OBJECTIVE: To compare hemodynamics and plasma big endothelin levels in patients awaiting heart transplantation who are receiving continuous IV therapy, and to establish their respective potency for predicting future cardiac events. DESIGN: A randomized, prospective trial of ambulatory continuous treatment with IV prostaglandin E(1) (PGE(1)) vs dobutamine. A subanalysis was conducted of all patients who completed 4 weeks of follow-up in regard to treatment effects on hemodynamics and big endothelin plasma levels. PATIENTS: Thirty-two listed heart transplant candidates who were refractory to oral treatment, 21 patients who were receiving PGE(1), and 11 patients receiving dobutamine. MEASUREMENTS AND RESULTS: Hemodynamics and plasma big endothelin levels were measured at baseline and after 4 weeks. The cardiac index increased significantly (PGE(1) group, 1.7 +/- 0.4 vs 2.5 +/- 0.6 L/min/m(2); dobutamine group, 1.8 +/- 0.3 vs 2.3 +/- 0.6 L/min/m(2); p < 0.05), whereas the systemic vascular resistance index (SVRI) decreased significantly only in the PGE(1) group (3,352 +/- 954 vs 2,178 +/- 519 dyne. s. cm(-5)/m(2); p < 0. 05). The plasma big endothelin level decreased significantly (PGE(1) group, 7.6 +/- 3.1 vs 4.7 +/- 2.6 fmol/mL; dobutamine group, 6.5 +/- 3.7 vs 5.0 +/- 2.6 fmol/mL; p < 0.01 for the time effect). Plasma big endothelin (beta = 0.393; chi(2) = 10.8; p = 0.001) and SVRI (beta = 0.003; chi(2) = 6.9; p < 0.01), both measured after 4 weeks of continuous treatment, were the only independent predictors of future outcome. CONCLUSION: Continuous treatment over 4 weeks with either PGE(1) or dobutamine in patients awaiting heart transplantation yields an improved hemodynamic state accompanied by a reduction of increased big endothelin levels. Plasma big endothelin measured after 4 weeks of continuous therapy provides prognostic information about future outcome.

Adult↗
PubMed2000

Increase in fragmented phosphatidylcholine in blood plasma by oxidative stress.

Oxidatively modified phospholipids with fragmented acyl chains have attracted much interest because of their proinflammatory activity and their potential involvement in atherosclerosis. They can be formed in vitro by free radical treatment of unsaturated phospholipids but it is not known under which conditions they accumulate in vivo. We assayed one species of fragmented phosphatidylcholine (PC) in human blood plasma by high performance liquid chromatography after precolumn derivatization with chloromethylanthracene. Structural analysis suggested that fragmented PC was a diacyl species with a palmitoyl group and a short oxidized residue, which most likely had four carbons. The concentration of fragmented PC was higher in elderly individuals with coronary heart disease than in young healthy controls. Smoking one cigarette acutely increased the concentration of fragmented PC in healthy adults. Fragmented PC also increased in the reperfusion period after treatment with cardiopulmonary bypass. The increase coincided with a surge of circulating neutrophils. In rats, the plasma concentration of fragmented PC was elevated by vitamin E deficiency and exposure to high oxygen. The data demonstrate that fragmented PC increases in blood plasma in response to various forms of oxidative stress.

Adult↗
PubMed1999

Cloning of breakpoints in and downstream the IGF2 gene that are associated with overexpression of IGF2 transcripts in colorectal tumours.

The human IGF2 gene belongs to a group of imprinted genes clustered on the short arm of chromosome 11, band p15.5. It contains 9 exons and spans over 30 kb. IGF2 mRNA overexpression has been reported in human tumours and in some inherited growth disorders. It was recently demonstrated that IGF2 mRNA overexpression contributes to tumour progression and that loss of parental imprinting as well as altered transcription factors are contributing to this overexpression. We have reported structural alterations in the 3' region of the IGF2 gene in two colorectal tumours that overexpressed the IGF2 transcript by 200- and 800-fold. We cloned by the vectorette-PCR strategy, genomic DNA fragments containing the breakpoints from these tumours. The sequencing of these fragments positioned the breakpoint 2 kb downstream the IGF2 gene in one tumour, and in exon 9 in the second. Both breakpoints occurred in regions containing repetitive elements: a TGGA repeat we have identified downstream the gene, and the (CA)n repetition in exon 9. We hypothesize that a negative regulatory element, located downstream the IGF2 gene, has been deleted following these structural alterations and leads to IGF2 gene overexpression.

Chromosome Aberrations↗
PubMed1999

Irregularity of the ventricular rhythm during atrial fibrillation: effect of slow atrioventricular nodal pathway ablation.

BACKGROUND: The contribution of dual atrioventricular (AV) nodal pathway physiology to the irregularity of the ventricular rhythm during atrial fibrillation has not been clarified. HYPOTHESIS: This study was performed to assess the effects of slow AV nodal pathway ablation on the irregularity of the ventricular rhythm during atrial fibrillation. METHODS: Irregularity of the ventricular rhythm was quantified using analysis of heart rate variability. In 20 patients with AV nodal reentrant tachycardia, absolute heart rate variability during atrial fibrillation was quantified before and after slow AV nodal pathway ablation by the standard deviation of all NN intervals (SDNN). Relative heart rate variability was determined by computing the coefficient of variation, SDNN normalized for the standard deviation of the mean ventricular cycle length (MVCL-AF). RESULTS: The slope of the regression between MVCL-AF and SDNN was significantly more gradual after slow pathway ablation (slope 0.39 vs. 0.23, p < 0.001). Coefficient of variation increased in 12 patients with heart rates > 120 beats/min at baseline (18.6 +/- 3.9 vs. 22.1 +/- 2.7% MVCL-AF, p < 0.05), but decreased in 8 patients with heart rates < 120 beats/min at baseline (25.6 +/- 3.1 vs. 22.2 +/- 2.2% MVCL-AF, p = 0.05). Furthermore, coefficient of variation correlated with MVCL-AF only at baseline (slope 0.034, r = 0.66), but no relation was found after slow pathway ablation (slope 0, r = 0). CONCLUSIONS: Slow AV nodal pathway ablation alters the relation between absolute heart rate variability and mean ventricular rate during atrial fibrillation and eliminates cycle length dependency of relative heart rate variability. These data indicate that dual AV nodal pathway physiology contributes to the irregularity of the ventricular rhythm during atrial fibrillation.

Adult↗
PubMed1999

Toxic methaemoglobin concentrations in premature infants after application of a prilocaine-containing cream and peridural prilocaine.

UNLABELLED: We report on a retrospective analysis of eight episodes of toxic methaemoglobinaemia in seven premature infants after the combined exposure to prilocaine by EMLA cream (12.5 mg prilocaine) and caudal anaesthesia (5.4-6.7 mg/kg prilocaine). The causative relationship between prilocaine and the infants' deterioration came to our attention through an anonymous voluntary incident-reporting system. The highest methaemoglobin concentration found was 30.6% (5.5 h after anaesthesia). All infants were symptomatic (mottled skin, paleness, cyanosis, poor peripheral perfusion) and two were exposed to unnecessary diagnostic and therapeutic procedures for unspecified deterioration in their conditions. Pharmacokinetic evaluation indicated a single compartment first-order elimination with a methaemoglobin half-life of 8 h. Normal levels (<1%) were reached 36 h after exposure to prilocaine. CONCLUSION: Whereas local skin application of prilocaine to premature babies is safe, peridural administration is not because premature infants are more sensitive to methaemoglobin inducing agents and tolerate methaemoglobinaemia less well.

Anesthesia, Caudal↗
PubMed1999

Moderate-intensity exercise training with elements of step aerobics in patients with severe chronic heart failure.

OBJECTIVE: To evaluate whether a specific program of moderate-intensity step aerobics training may be sufficient to improve the exercise tolerance of patients with severe chronic heart failure. PATIENTS: Twenty-six patients (22 men, 4 women; mean +/- SD age, 54 +/- 9yrs) with a history of severe chronic heart failure (left ventricular ejection fraction of 18% +/- 8%). STUDY DESIGN: Prospective, randomized, controlled trial. Patients were randomized into exercise and control groups. All patients underwent a clinical examination and a ramp pattern cycle exercise test before and after the observation period. The exercise group underwent a moderate-intensity (50% of peak oxygen uptake) 12-week training program, progressing to 100 minutes per week of step aerobics and 50 minutes per week of cycling. The control group did not perform a training program. MAIN OUTCOME MEASURES: Peak oxygen uptake, peak workload, percent of predicted power ability. RESULTS: Significant increases in peak oxygen uptake (15 +/- 3.4 to 18.5 +/- 2.9mL/kg/min; p = .001), peak workload (77 +/- 26 to 99 +/- 31 watts; p = .000), and percent of predicted power ability (43% +/- 10% to 56% +/- 13%; p = .000) were observed in the exercise group. No significant changes in baseline parameters occurred in the control group. There were no critical changes in heart rate or blood pressure in either group. CONCLUSION: Moderate-intensity step aerobics training significantly increases peak oxygen uptake and peak workloads in patients with severe chronic heart failure.

Aged↗
PubMed1999

Leginon: a system for fully automated acquisition of 1000 electron micrographs a day.

We have developed a system to automatically acquire large numbers of acceptable quality images from specimens of negatively stained catalase, a biological protein which forms crystals. In this paper we will describe the details of the system architecture and analyze the performance of the system as compared to a human operator. The ultimate goal of the system if to automate the process of acquiring cryo-electron micrographs.

Automation↗
PubMed1999

Bridging to heart transplantation: prostaglandin E1 versus prostacyclin versus dobutamine.

BACKGROUND: Prostaglandin E1 (PGE1) and prostacyclin have potent pulmonary and systemic vasodilating properties. This prospective, randomized trial compared PGE1 vs prostacyclin vs. low-dose dobutamine in patients with low-output heart failure awaiting heart transplantation (HTx) who were refractory to oral treatment. METHODS: Patients in advanced heart failure in New York Heart Association (NYHA) Class IV, with a cardiac index < or = 2.5 L/minute/m2 and a pulmonary capillary wedge pressure > or = 20 mmHg, who were listed for HTx were studied. In an inpatient study phase of 12 hours duration, therapy was aimed to increase cardiac output by 20% or more, when compared to baseline values, and to achieve a reduction of pulmonary vascular resistance below 550 dyn.s/cm-5m-2. During a long-term outpatient phase, the drugs were continuously infused to bridge these patients to HTx using three combined negative endpoints (worsening heart failure, serious adverse events, death) for analysis. RESULTS: Sixty-eight patients were enrolled, 30 patients on PGE1, 8 patients on prostacyclin, and 30 patients on dobutamine. During the inpatient study phase, maximum doses were 22 +/- 1.8 ng/kg/minute for PGE1, 7 +/- 1 ng/kg/minute for prostacyclin and 5 +/- 0.4 micrograms/kg/minute for dobutamine. During the inpatient study phase 21 patients failed, 4/30 (13%) patients on PGE1, 4/8 patients on prostacyclin (50%), and 13/30 (43%) on dobutamine (p < 0.05). Long-term continuous intravenous drug infusion in outpatients was begun in 26 patients on PGE1, in 4 patients on prostacyclin, and in 17 patients on dobutamine. Infusion therapy lasted for 88 +/- 14 days in the PGE1 group with 31 +/- 22 days in the prostacyclin group, and 30 +/- 8 days in the dobutamine group (NS). During the outpatient phase 23 patients reached a negative endpoint with 16 patients developing worsening heart failure, 5 severe adverse events and 2 deaths. Seven out of 26 (27%) failed on PGE1, 4/4 (100%) failed on prostacyclin, and 12/17 (71%) failed on dobutamine (p < 0.05, log rank test). Because prostacyclin treatment was ineffective in the first 8 patients, this trial arm was stopped prematurely. CONCLUSIONS: The findings from this prospective open pilot trial suggest that continuous PGE1 infusions at individualized dosages can be useful in certain patients as a pharmacologic bridging procedure with reduced risk to develop worsening heart failure before HTx compared to prostacyclin and dobutamine. Further comparative studies are warranted to investigate the effects of PGE1 among other bridging agents.

Alprostadil↗