Polyethylene glycol-coated collagen patch (hemopatch®) in open partial nephrectomy.

PURPOSE: To describe the results of a polyethylene glycol-coated collagen patch, Hemopatch® on blood loss, surgical time and renal function in partial nephrectomy (PN) for renal cell carcinoma (RCC). METHODS: Out of a single surgeon cohort of n = 565 patients undergoing conventional open PN (CPN) between 01/2015 and 12/2017 at the University of Munich a consecutive subgroup (n = 42) was operated on using a polyethylene glycol-coated collagen-based sealant Hemopatch® (Baxter International Inc., Deerfield, IL, USA) (HPN). RESULTS: Median age was 65.2 years (range 12.7-95.2) with median follow-up of 9.43 months (0.03-49.15). Baseline renal function (CKD-EPI) was 78.56 ml/min/1.73 m2 (range 20.38-143.09) with a non-significant decline to 74.78 ml/min/1.73 m2 (range 3.75-167.74) at follow-up. In CPN 46% had low complexity, 33% moderate complexity and 20% high complexity lesions with 33% low, 40% moderate and 27% high complexity masses in HPN. Median tumor size was 4.3 cm (range 1-38 cm) in CPN with 4.8 cm (range 3.8-18.3 cm) with HPN, p = 0.293. Median blood loss and duration of surgery was significantly lower in the HPN group vs. CPN (146 ml ± 195 vs. 114 ml ± 159 ml; p = 0.021; 43 min ± 27 for HPN vs. 53 min ± 49; p = 0.035) with no difference in clamping time (12.6 min ± 8.6 for HPN vs. 12.0 min ± 9.5; p = 0.701). CONCLUSIONS: Hemopatch® supported renoraphy shows promising results compared to standard renoraphy in PN. No side effects were seen. Further studies should evaluate the prevention of arterio-venous or urinary fistulas. In complex partial nephrectomies Hemopatch® supported renoraphy should be considered.

18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results.

INTRODUCTION: Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. METHODS: 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8 weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. RESULTS: Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. CONCLUSION: On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT.

Advanced Molecular Imaging in Histologically Verified Metanephric Adenoma.

Metanephric adenoma (MA) describes a rare renal tumor and is generally considered a benign lesion. However, there are cases with regional lymphogenic and distant metastases. Noninvasive diagnosis of MA using conventional imaging remains challenging. Here, we describe a case of histologically verified MA with additional advanced molecular imaging consisting of 18F-PSMA-1007 PET/CT, 99mTc-Sestamibi SPECT and contrast-enhanced ultrasound.

Mid-term follow up of mitral valve reconstruction due to active infective endocarditis.

BACKGROUND AND AIM OF THE STUDY: Mitral valve reconstruction in patients with acute endocarditis (AE) is a challenging operation which prompts the surgeon into immediate action. This report summarizes the mid-term results of 22 patients who required mitral valve reconstruction due to AE. METHODS: Mean patient age was 46 years (range: 20-79 years); mean follow up was 46 months (range: 1-90 months). Preoperatively, >70% of patients had severe mitral regurgitation and were in NYHA functional class III. Surgical techniques used were annuloplasty (n = 16; 10 with Carpentier ring, five Wooler-Kay and one Frater); suture closure of the perforation (n = 1), patch closure of the perforation (n = 5), leaflet resection with primary closure (n = 2), leaflet resection with patch closure (n = 8), and chordal transfer (n = 3). Additional surgery included CABG (n = 3) and De Vega plasty (n = 4). Aortic valve replacement or reconstruction (n = 9) included one mechanical valve, one bioprosthesis, one reconstruction and six homografts. Patients were followed up annually in our outpatient department and/or by questionnaires. RESULTS: Two patients died perioperatively due to either low output syndrome or uncontrolled sepsis. There were three reoperations; two of these were successful, and one patient subsequently died. In addition, one patient died six years after operation due to prostatic cancer, and one seven years later due to progressive heart failure. At the last follow up, 15 patients were in NYHA class I (68%) and five in class II (23%); no or only mild mitral insufficiency was seen on transthoracic echocardiography (91%). The estimated survival rate at 60 months was 87 +/- 12.7%, and 12 patients were followed up for >60 months. No incidence of recurrent valve infection occurred. CONCLUSION: Mitral valve reconstruction in patients with AE shows a low incidence of valve-related complications with promising postoperative functional results and mid-term survival. On this basis, mitral valve reconstruction for mitral insufficiency secondary to AE may be recommended as a valve salvage treatment, when it is technically possible.

Epinephrine application via an endotracheal airway and via the Combitube in esophageal position.

OBJECTIVE: To compare plasma concentrations and cardiovascular effects of epinephrine after application via a conventional endotracheal airway and via the esophageal lumen of a new emergency airway, the esophageal tracheal Combitube. DESIGN: Prospective, randomized study. SETTING: Center for Biomedical Research, University of Vienna. SUBJECTS: Fourteen juvenile swine received either an endotracheal tube (Group A) or a Combitube in esophageal position (Group B). INTERVENTIONS: In Part I of the study, epinephrine was administered during spontaneous beating of the heart; in Part II, epinephrine was administered during cardiopulmonary resuscitation, using a ten-fold higher dosage in Group B, respectively. MEASUREMENTS: Plasma epinephrine levels were measured 1, 2, 3, 5, 7, 10, 15, and 30 mins after application. Systolic arterial blood pressure and cardiac output in Part I, and end-tidal CO2 and coronary perfusion pressure in Part II were recorded. MAIN RESULTS: In Part I, increased levels of plasma epinephrine and systolic arterial pressure were maintained significantly longer in Group B when compared with Group A. In Part II, no significant differences between the groups were found with regard to plasma epinephrine levels and hemodynamic variables. CONCLUSION: Epinephrine applied via the esophageal lumen of the Combitube in a ten-fold higher dosage has similar effects on plasma epinephrine levels and hemodynamic variables compared to endotracheal administration.

Does the Ross operation fulfil the objective performance criteria established for new prosthetic heart valves?

BACKGROUND AND AIM OF THE STUDY: Objective Performance Criteria (OPC) were established to compare a new heart valve prosthesis with fixed standards of linearized complication rates for morbid events: thromboembolism, thrombosis, hemorrhage, leakage and endocarditis. Although the pulmonary autograft operation provides optimal hemodynamic performances, the morbidity of both the autograft and homograft remain topics of controversy. METHODS: Valve-related morbid events and echocardiography in 109 patients who have undergone the Ross operation since 1991 were evaluated at annual follow up examination (mean 2.8 years; range: 1 month to 8 years). Linearized rates (number of events per 100 years patient exposure) were calculated to establish the safety and efficacy of this operation (288.7 years cumulative patient-years). RESULTS: Three patients died perioperatively (2.8%); two patients were reoperated due to autograft incompetence (1.8%, both valve repairs). No patient is currently on anticoagulation therapy, and no events of thromboembolism, valve thrombosis or bleeding were observed during follow up. Two patients had homograft endocarditis but were asymptomatic with moderate incompetence at the last follow up examination. There was no significant increase in aortic incompetence (AI) or pulmonary incompetence (PI) between discharge and follow up (AI, 0.4 +/- 0.5 versus 0.6 +/- 0.6; PI, 0.2 +/- 0.4 versus 0.4 +/- 0.6). In comparing the OPC (events per patient-year) for the Ross operation with those for tissue and mechanical valves, the results were: thromboembolism 0% (tissue 2.5%, mechanical 3%), valve thrombosis 0% (0.2% and 0.8%), all bleeding 0% (1.4% and 3.5%), major bleeding 0% (0.9% and 1.5%), all leakage 0.7% (1.2% and 1.2%), major leakage 0.7% (1.2% and 1.2%) and endocarditis 0.7% (1.2% and 1.2%). CONCLUSION: The pulmonary autograft procedure provides optimal hemodynamics and echocardiographic performance, and low valve-related complication rates; thus, the OPC for tissue and mechanical heart valve prostheses can be fulfilled by this technically demanding operation. These results confirm that the autograft is an ideal aortic valve replacement device.

[Skeletal muscle strength following orthotopic heart transplantation]. / Kraftstatus der Skelettmuskulatur nach orthotoper Herztransplantation.

AIM OF THE STUDY: Strength measurement of thigh muscles of patients after orthotopic heart transplantation (HTX) with a sedentary lifestyle, entering a cardiac rehabilitation program. DESIGN: Cross-sectional study; values are compared to patients with chronic heart failure (CHF) and healthy controls. METHODS: Isometric and isokinetic peak torque of knee extensor and flexor muscles measured on a Cybex 6000. Twenty minutes' muscle fatigue test of knee extensor muscles. Test of motor tasks of daily living. RESULTS: HTX group: n = 18, age 59 +/- 7 years, body mass index (BMI) 29 +/- 5, months after HTX 46 +/- 36 months; CHI group: n = 24, age 55 +/- 8 years, BMI 25 +/- 4, months after CHF 19 +/- 16 months; control group: n = 10, age 55 +/- 6 years, BMI 26 +/- 5. The HTX group differed significantly (p < 0.05) from the CHI group. Peak torque of knee extensor muscles: HTX: 120.3 +/- 8.4; CHI: 127.8 +/- 8.0 Nm; controls: 158.3 +/- 5.5 (ANOVA p < 0.05); peak torque of knee flexor muscles: HTX 65.6 +/- 5.9 Nm; CHI 70.1 +/- 6.2 Nm; controls 84.4 +/- 3.1 Nm(ANOVA p < 0.01). Peak torque of knee extensor muscles related to body weight: HTX: 137.4 +/- 10.0 Nm%, CHI: 162.6 +/- 9.3 Nm%, control group 202.8 +/- 5.7 Nm% (ANOVA p < 0.01). Muscle fatigue test of knee extensor muscles: isometric maximal strength (maximal voluntary contraction, MCV; HTX vs. CHI): 331.6 +/- 14.7 N vs. 335.5 +/- 18.6 N (n.s.), MVC after 5 minutes 296.3 +/- 15.7 N vs. 288.4 +/- 16.7 N; MVC after 10 minutes: 283.5 +/- 15.7 N vs. 282.5 +/- 17.7 N; MVC after 15 minutes 275.7 +/- 13.7 N vs. 280.6 +/- 21.6 N. No significant differences between groups were observed. All values were significantly lower than those of healthy controls (406.2 N; 385.9 N; 373.7 N and 369.6 N). There was a significant decline in MVC after 5 minutes compared to initial values (p < 0.01), in both patients groups but not in the control group. No further decline in MVC was observed beyond the 5th minute of the fatigue test (p > 0.05). CONCLUSION: Peak torque related to body weight and muscle endurance of knee extensor muscles of sedentary patients after orthotopic HTX do not significantly differ from those of comparable patients with CHF but do differ from those of healthy controls. Specific training of muscle strength is needed for patients even several years after orthotopic heart transplantation.

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.

[Improved kidney function with intravenous prostaglandin E1 in patients with terminal heart failure]. / Verbesserung der Nierenfunktion durch intravenöses Prostaglandin E1 bei Patienten mit terminaler Herzinsuffizienz.

In end stage congestive heart failure activation of a series of compensatory mechanisms increase renal vascular resistance and impair renal function. Prostaglandin E1 is increasingly used in the treatment of severe heart failure for its vasodilating actions. In various experimental settings prostaglandin E analogues are known to improve renal function by modulating renal filtration pressure and redistribution of renal blood flow. However, prostaglandin E1 decreases systemic blood pressure and thus, also renal perfusion pressure, a fact by which renal function might be further compromized in heart failure patients. The aim of the study was to evaluate the effects of prostaglandin E1 on excretory renal function in patients with end stage heart failure and to prove the hypothesis, that the well known local actions of prostaglandins on renal microcirculation might outweigh the negative impact of an expected decrease in perfusion pressure. 25 patients with terminal congestive heart failure were investigated. 13 patients received prostaglandin E1 at a dose of 13.5 +/- 1.9 ng/kg/min in combination with constant rates of dopamine and dobutamine (group A), 12 patients received prostaglandin E1 at a dose of 10.3 +/- 1.7 ng/kg/min without catecholamines (group B). There was no significant difference in prostaglandin dosages between groups. Kidney function was assessed by measuring plasma creatinine and urea nitrogen, urinary output, creatinine clearance, osmotic and free water clearance at baseline and after 72 h of infusion therapy. Hemodynamic parameters were measured by using a balloon tipped pulmonary arterial catheter. Hemodynamic measurements during infusion showed a significant improvement in all patients. At the same time as expected mean arterial pressure decreased in both groups (p < 0.001). Nevertheless, in both groups a significant increase of creatinine clearance during infusion was observed (in group A from 45 ml/min to 78 ml/min., p < 0.05, in group B from 59 ml/min to 105 ml/min., p < 0.001). Creatinine clearance in group B (without catecholamines) reached higher levels than group A (p < 0.05). Urinary volumes did not change during infusion therapy, whereas free water clearance significantly decreased, as an indication of an improvement of renal concentrations ability. We conclude, that in patients with end stage heart failure continuous infusion of prostaglandin E1 improves excretory kidney function. These findings suggest that the local effects of prostaglandin E1 on renal microcirculation can counterregulate the negative impact of prostaglandins on renal perfusion pressure.

Hemodynamic and neurohumoral effects of long-term prostaglandin E1 infusions in outpatients with severe congestive heart failure.

BACKGROUND: Prostaglandins of the E type are potent endogenous vasodilators that also interfere with the activity of the sympathetic nervous system. Thus treating patients with end-stage heart failure with prostaglandin E1 (PGE1) infusions seems to accord well with the hypothesis that neurohumoral imbalance rather than hemodynamic derangements should be the priority in the treatment of heart failure. METHODS: We sought to investigate neurohumoral in addition to hemodynamic changes during long-term PGE1 infusion and determined plasma renin activity, atrial natriuretic peptide, norepinephrine, and big endothelin plasma levels in 13 male patients with heart failure whose symptoms remained severe in spite of optimized oral therapy with digitalis, nitrates, furosemide (185 +/- 72 mg/d) and enalapril (33 +/- 3 mg/d). PGE1 infusion rate was started with 2.5 ng/kg/min and stepwise increased to the maximum tolerated dose (26 +/- 4 ng/kg/min), which was halved for continuous infusion through the following 12 hours and further stepwise reduced to an average dose of 8 +/- 1 ng/kg/min. Right heart catheterization was performed for acute hemodynamic studies and after 4 weeks. All patients were discharged with a catheter that was connected to a portable pump for home therapy. RESULTS: Acute effects of PGE1 were reductions in systemic blood pressure, (p < 0.05), right atrial pressure (p < 0.001), pulmonary artery pressure (p < 0.05), pulmonary capillary wedge pressure (p < 0.01), systemic and pulmonary vascular resistance index (both p < 0.01) and an increase in cardiac and stroke volume index (both p < 0.001) without a change in heart rate. After 4 weeks a persistent increase from baseline in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.2 L/min/m2; p < 0.01) and in pulmonary vascular resistance index (from 479 +/- 50 to 331 +/- 29 dynes x sec/cm5 x m2; p < 0.05) was observed. Atrial natriuretic peptide (p < 0.05) decreased, and norepinephrine and big endothelin showed a tendency to a lower level. Concomitantly, New York Heart Association functional class changed (p = 0.0001), with one patient's condition remaining class IV, the conditions of seven patients decreasing to class II, and the conditions of five patients decreasing to class III. CONCLUSION: Thus long-term parenteral home therapy with PGE1 infusions in patients with severe end-stage heart failure elicited beneficial clinical and hemodynamic effects without activating neurohumoral counterregulatory systems.

Five-year follow-up after heart valve replacement with the CarboMedics bileaflet prosthesis.

BACKGROUND: The CarboMedics valve is a relatively new, low-profile, bileaflet, mechanical prosthesis. The results of a prospective follow-up study after valve replacement with this prosthesis in a university hospital are presented. METHODS: We implanted 640 CarboMedics prostheses in 583 patients in the aortic (n = 359), mitral (n = 167), or aortic and mitral positions (double valve replacement; n = 57). Patient ages ranged from 11 to 81 years (mean age, 58 +/- 12.3 years). RESULTS: Overall hospital mortality was 9.0%; however, when high-risk urgent cases were removed from the calculation, the operative mortality fell to 4.5%. Follow-up was 98% complete, comprising 2,027 patient-years for a mean follow-up of 44 months (range, 6 to 72 months). Actuarial freedom from complications (linearized rates in parentheses) was as follows: late mortality, 85% +/- 2.0% (2.3%/patient-year); thromboembolism, 92% +/- 1.1% (1.6%/patient-year); anticoagulation-related hemorrhage, 87% +/- 1.2% (2.8%/patient-year); prosthetic valve endocarditis, 98% +/- 0.5% (0.1%/patient-year); and overall valve-related morbidity and mortality, 76% +/- 2.1% (4.3%/ patient-year). CONCLUSIONS: The CarboMedics valve shows a low rate of valve-related complications comparable with other new mechanical heart valve prostheses.

Prostaglandin E1--bridge to cardiac transplantation. Technique, dosage, results.

BACKGROUND: Heart transplantation candidates who remain severely symptomatic despite therapy are normally hospitalized. Continuous infusion of intravenous drugs from a portable pump may allow such patients to live a fairly active life until a donor heart is found. AIM: To investigate in an open pilot study if heart transplantation can be safely accomplished if these patients are continuously bridged with various regimens including inotropic support with low-dose dobutamine in conjunction with dopamine and prostaglandin E1. METHODS: We report on 5 years' experience with prostaglandin E1, a potent vasodilator with proven efficacy in severe heart failure when coupled with catecholamines. From 1990 to 1995 54 heart transplantation candidates were bridged with prostaglandin E1 in addition to dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 (group A; n = 32) or in addition to 3 micrograms.kg-1 min-1 dopamine alone (group B; n = 22), and 11 heart transplantation candidates were bridged with dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 only (group C; n = 11). In an initial dose-ranging test, prostaglandin E1 was uptitrated to side effect limit (29 +/- 1 ng.kg-1.min-1). Haemodynamics, except for stroke volume index, were similar in all patients at baseline and a sufficient haemodynamic response (20% increase in stroke volume) was observed during the acute study. Fifty percent of the peak dose was used for initiating chronic therapy; the dose of prostaglandin E1 was further reduced if side effects recurred. RESULTS: Twenty-nine (54%) patients in groups A and B and six in group C could be discharged home with chronic therapy via a Hickman catheter connected to a portable pump. After 4 weeks in six patients in group A and in 13 patients in group B, when prostaglandin E1 had been reduced from 15 +/- 2 ng.kg-1.min-1 to 8 +/- 1 ng.kg-1 min-1 increases in cardiac index and decreases in systemic vascular resistance were sustained, and a permanent decrease in pulmonary vascular resistance index was observed in group B. Intravenous therapy was changed in nine patients (3/1/5) because of side effects and worsening heart failure. Prostaglandin E1 was withdrawn in three of these patients because of an increase in serum creatinine (3 mg.100 ml-1), and in one because of noncompliance. In total, there were 17 cardiac deaths (9/6/2), 42 heart transplants (22/14/6) and six (1/2/3) weaned survivors (including one non-cardiac death) in this study. Overall outcome was similar in groups A and B, but distribution after 2 months appeared to be different (P < 0.05) based on more transplantations in group A. CONCLUSION: We concluded that chronic infusions with prostaglandin E1 at reduced dosages is a feasible and safe therapeutic adjunct to bridge end-stage heart failure patients and may yield desirable effects in a subset of patients in the absence of inotropic support by dobutamine.

Acceptance of a pump-driven infusion therapy with prostaglandin E1 as a bridge to heart transplantation.

Ambulatory pump-driven intravenous infusions are a novel and - compared with hospitalization-cost-effective procedure to bridge refractory heart failure patients to cardiac transplantation. In the present study 13 patients received chronic infusions with prostaglandin E1 alone or in conjunction with catecholamines and the acceptance of this bridging therapy was investigated over a period of seven weeks. Prostaglandin E1 was uptitrated from 2.5 ng/kg/min to a maximum of 40 ng/kg/min, according to individual tolerance. 50% of the maximum tolerated dose of prostaglandin E1 was used for chronic infusion with a further dose reduction if side effects occurred. Altogether 8 patients who completed the therapy were analysed; of the remaining 5 three patients had a heart transplant, one patient died and one patient did not comply with the protocol. The drugs were administered by an automatic portable pump, which was connected to a subcutaneous tunneled catheter. During hospitalization patients and their relatives were instructed how to prepare drug solutions and to handle the infusion system. Patients' perceptions were investigated by visual analog scale questionnaires (rating scale zero to ten) before, and at weekly intervals during bridging therapy. Initial acceptance was documented as belief in therapy (9.4 +/- 1.2 SD), absence of fear of handling the pump (8.9 +/- 1.2 SD) and confidence of receiving help of close relatives (8.7 +/- 1.8 SD). During the observation period there were no statistically significant differences compared with this favorable starting position and no significant disruption of life style occurred. Pain in the joints-a prostaglandin E1-associated side effect-increased significantly (p < 0.05) at week 5, but returned to baseline levels during the following two weeks. At study end patients confirmed that they would repeat the experience (7.6 +/- 1.4 SD) and advise other patients to undergo this form of therapy (8.2 +/- 1.9 SD). Thus, this pilot study suggests that ambulatory pump-driven intravenous infusion therapy comprising prostaglandin E1 and catecholamines is acceptable to patients as a bridge to heart transplantation and that there should be no major difficulties regarding compliance.

Ca(2+)-channel blockers modulate the expression of interleukin-6 and interleukin-8 genes in human vascular smooth muscle cells.

Ca(2+)-channel blockers at therapeutic concentrations were shown to modulate several processes underlying inflammation, such as growth factor-mediated activation of genes coding for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in human vascular smooth muscle cells (VSMC) (Block et al., 1991), and for interleukins in human mesangial cells (Roth et al., 1992). Two Ca(2+)-channel blockers, Manidipine (Roth et al., 1992) and Verapamil (Walz et al., 1990) have been shown to induce the expression of the gene coding for interleukin-6 (IL-6). Here we demonstrate that the four Ca(2+)-channel blockers, Amlodipine, Felodipine, Isradipine and Manidipine, at nanomolar concentrations, activate the transcription of the genes encoding IL-6 and IL-8 in primary human VSMC and fibroblasts. Ca(2+)-channel blocker-induced transcription is subsequently followed by secretion of the two ILs into the growth medium of the cells. In addition, we compared the action of the Ca(2+)-channel blockers with that of propranolol, a beta-adrenoceptor antagonist, or with furosemide, a diuretic, all of which are known to lower blood pressure. However, in contrast to the dihydropyridines, the two latter drugs failed to affect the expression of the two IL genes.

Elective surgery for blunt cardiac trauma.

The cases of eight patients who underwent elective surgery for blunt cardiac trauma are presented. All but one experienced multiple trauma and the median Injury Severity Score was 26 (range, 18-59). A posttraumatic cardiac defect was diagnosed from 1 day up to 6.5 years (median, 3 weeks) after the accident. These included mitral regurgitation (n = 4), ventricular septal defect (n = 2), atrial septal defect with mitral regurgitation (n = 1), and ventricular aneurysm (n = 1). Elective cardiac surgery was performed from 4 weeks up to 12 years after the traumatic event (median, 18.5 months). A history of blunt chest trauma requires careful clinical follow-up supported by echocardiography in asymptomatic patients. Surgical therapy is performed according to standard techniques and the results are comparable with those of non-trauma surgery.

Beneficial hemodynamic effects of prostaglandin E1 infusion in catecholamine-dependent heart failure: results of a prospective, randomized, controlled study.

OBJECTIVE: To study the hemodynamic effects of prostaglandin E1 (PGE1) administered in addition to a standard catecholamine infusion in patients with severe chronic heart failure. DESIGN: Prospective, placebo-controlled, randomized, single-blind study. SETTING: Intensive care unit at a university hospital. PATIENTS: Thirty patients with severe chronic heart failure, New York Heart Association functional class IV (28 men, two women, with a mean age of 54 +/- 2 yrs, mean left ventricular ejection fraction 10 +/- 0.6%). All patients received oral therapy with digitalis, furosemide (mean dose 300 +/- 46 mg/day), and enalapril (20 +/- 2.7 mg/day). INTERVENTIONS: Hemodynamic measurements using pulmonary artery flotation catheters were performed at baseline, > or = 24 hrs after standardized catecholamine infusion with dopamine (3 micrograms/kg/min) and dobutamine (5 micrograms/kg/min), as well as 48 hrs after randomization to infusion therapy with PGE1 (30 ng/kg/min) or a placebo. MEASUREMENTS AND MAIN RESULTS: The addition of PGE1 to an ongoing catecholamine infusion in 20 patients caused a 16 +/- 4% decrease in mean pulmonary arterial pressure (p < .001), a 22 +/- 5% decrease in pulmonary artery occlusion pressure (p < .0001), a 24 +/- 8% decrease in pulmonary vascular resistance index (p < .001), a 20 +/- 9% decrease in right atrial pressure (p < .01), a 14 +/- 3% decrease in mean arterial pressure (p < .001), and a 29 +/- 4% decrease in systemic vascular resistance index (p < .0001). These PGE1-induced decreases occurred without a change in heart rate. Stroke volume index increased with PGE1 therapy by 34 +/- 7% (p < .0001), and cardiac index increased by 34 +/- 6% (p < .0001). No hemodynamic changes were observed during combined infusion with catecholamines and placebo in ten patients. CONCLUSION: PGE1 improves the hemodynamic state in end-stage chronic heart failure patients already receiving a standard dose dopamine/dobutamine infusion.

Doppler sonographic evaluation of the Duromedics-Edwards bileaflet valve at five-year follow up.

In order to define normal flow characteristics at mid-term follow up, prospective Doppler echocardiographic studies were performed in 145 patients (mean age 49.3 years) with Duromedics-Edwards bileaflet valve prostheses (76 aortic, 55 mitral and 14 double aortic and mitral) at a mean interval of 5.2 years following operation. All patients had clinically normal prosthetic valve function and no clinical or radiographic signs of heart failure. None of the patients had severely impaired left ventricular function as assessed by cross sectional 2D echocardiography. Mean peak velocity across prostheses in the aortic position was 2.8 +/- 0.5 m/sec, corresponding to a calculated instantaneous peak pressure gradient of 31.4 +/- 10.2 mmHg. Gradients varied inversely to valve size, although differences were significant only when comparing the 19mm and 21mm versus the 27mm valve (p < 0.05). In the mitral position the mean of peak velocity was 1.8 +/- 0.3 m/sec and pressure half time was 102 +/- 14 msec, representing a calculated mean orifice size of 2.2 +/- 0.5 cm2, with no significant difference between valves of different sizes. Paravalvular regurgitation was more common in the aortic than in mitral position (39% vs. 4%, p < 0.05), although in all cases it was mild (range less than one centimeter from prosthesis ring) and clinically insignificant. We conclude that normally functioning DE valve prostheses have a predictable range of Doppler echocardiographic parameters, although the individual variability of pressure gradients and effective valve area (in mitral valves) has to be emphasized. Nevertheless, the Duromedics Edwards valve shows good hemodynamic properties at mid-term follow up.