Are minimized perfusion circuits the better heart lung machines? Final results of a prospective randomized multicentre study.

INTRODUCTION: Minimized perfusion circuits (MPCs), although aiming at minimizing the adverse effects of cardiopulmonary bypass, have not yet gained popularity. This can be attributed to concerns regarding their safety, as well as lack of sufficient evidence of their benefit. METHODS: Described is a randomized, multicentre study comparing the MPC - ROCsafeRX to standard cardiopulmonary bypass in patients undergoing elective coronary artery bypass grafting and/ or aortic valve replacement. RESULTS: Five hundred patients were included in the study (252 randomized to the ROCsafeRX group and 248 to standard cardiopulmonary bypass). Both groups were well matched for demographic characteristics and type of surgery. No operative mortality and no device-related complications were encountered. Transfusion requirement (333 ± 603 vs. 587 ± 1010 ml; p=0.001), incidence of atrial fibrillation (16.3% vs. 24.2%; p=0.03) and the incidence of major adverse events (9.1% vs. 16.5%; p=0.02) were all in favour of the MPC group. CONCLUSION: These results confirm both the safety and efficacy of the ROCsafeRX MPC for a large variety of cardiac patients. Minimized perfusion circuits should, therefore, play a greater role in daily practice so that as many patients as possible can benefit from their advantages.

Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI) : Joint Consensus Document of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V. (ALKK) and cooperating Cardiac Surgery Departments.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4-8%) as well as in low-risk patients (STS-Score < 4%). However, risk scores exhibit limitations and, as a single criterion, are unable to establish an appropriate indication of TF-TAVI vs transapical TAVI vs SAVR (surgical aortic valve replacement). The ESC (European Society of Cardiology)/EACTS (European Association for Cardio-Thoracic Surgery) guidelines 2017 and the German DGK (Deutsche Gesellschaft für Kardiologie)/DGTHG (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie) commentary 2018 offer a framework for the selection of the best therapeutic method, but the individual decision is left to the discretion of the heart teams. An interdisciplinary TAVI consensus group of interventional cardiologists of the ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V.) and cardiac surgeons has developed a detailed consensus on the indications for TF-TAVI to provide an up-to-date, evidence-based, comprehensive decision matrix for daily practice. The matrix of indication criteria includes age, risk scores, contraindications against SAVR (e.g., porcelain aorta), cardiovascular criteria pro TAVI, additional criteria pro TAVI (e.g., frailty, comorbidities, organ dysfunction), contraindications against TAVI (e.g., endocarditis) and cardiovascular criteria pro SAVR (e.g., bicuspid valve anatomy). This interdisciplinary consensus may provide orientation to heart teams for individual TAVI-indication decisions. Future adaptations according to evolving medical evidence are to be expected. Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI).

[Determination of ventricular volumes in coronary artery disease: comparison of two gated SPECT analysis tools with MRI]. / Bestimmung ventrikulärer Volumina bei koronarer Herzerkrankung: Vergleich zweier Gated-SPECT-Analyseverfahren mit MRT.

AIM: Comparison of two gated SPECT analysis tools -- gated SPECT quantification (GSQ) and emory cardiac toolbox (ECT) -- in patients with coronary artery disease (CAD) and severely impaired left ventricular function (preoperative: EF <35% by cardiac catheter). PATIENTS, METHODS: A total of 56 gated SPECT examinations (one-day hybrid-protocol with (201)Tl-chloride for rest and (99m)Tc-sestamibi for stress applied during low-dose dobutamine stress MR-examination; temporal resolution; 8 phases per cardiac cycle) were performed in 36 patients (31 preoperatively, 25 postoperatively) and compared with MRI in 48 cases. Left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes as well as the left ventricular ejection fraction (LV-EF) were calculated. RESULTS: The total volumetric assessment by both analysis algorithms (n = 56) showed good intraclass correlation coefficients preoperatively (n = 31), but even better postoperatively (n = 25). The mean reconstruction time was approximately 3 minutes ( +/- 2 SD) for GSQ and 15 minutes ( +/- 5 SD) for ECT. In comparison to MRI the results of both analysis tools also correlated well, but the agreement decreased in the presence of scared tissue. The mean LV-EF (MRI) preoperatively was 30.4%, in 6/36 patients above the values calculated from cardiac catheter, postoperatively 34.6%. CONCLUSION: Both gated SPECT analysis tools showed reliable volumetric assessments in high-risk patients with CAD and severely reduced LV-EF in comparison to MRI, with advantages for GSQ in terms of postprocessing time. However, for the calculation of LV-EF a markedly lower concordance with MR-results was observed for both methods depending on the presence of myocardial scars.

Decreased plasma concentration of brain natriuretic peptide as a potential indicator of cardiac recovery in patients supported by mechanical circulatory assist systems.

OBJECTIVES: We sought to investigate the relationship between the plasma concentration of brain natriuretic peptide (BNP), echocardiographic findings and the clinical outcome of patients supported with ventricular assist devices (VADs) to determine the role of BNP as a predictor for cardiac recovery. BACKGROUND: Ventricular unloading in patients with end-stage heart failure supported by VADs may lead to myocardial recovery. The BNP is produced in the myocardium in response to chronic volume overload, but the effects on it of ventricular unloading by VADs are largely unknown. METHODS: Twenty-one patients diagnosed with nonischemic cardiomyopathy and supported by VADs were evaluated for echocardiographic data and blood chemistry including BNP. They were divided into patients who died while on mechanical support (group I; n = 9), patients who were transplanted (group II; n = 8) and patients who were successfully weaned off the system and did not require transplantation (group III; n = 4). RESULTS: Brain natriuretic peptide plasma concentrations decreased significantly after initiation of mechanical circulatory support (p = 0.017). Furthermore, the changes in BNP plasma concentrations showed a faster decrease to normal levels within the first week after implantation of the VAD in patients who were weaned off the system (group III) compared to patients in group I and group II. CONCLUSIONS: This study shows that ventricular unloading with VADs decreases BNP plasma concentrations in patients who suffer from end-stage heart failure. Furthermore, we hypothesize that an early decrease of BNP plasma concentration may be indicative of recovery of ventricular function during mechanical circulatory support.

Characterization of the 5'-flanking promoter region of the rat somatostatin receptor subtype 3 gene.

We investigated the 5'-flanking promoter region of the rat somatostatin receptor subtype 3 (rSSTR3). Using a cDNA probe, genomic clones containing the 5'-flanking promoter region of the rSSTR3 gene were isolated. A sequence of 5.4 kb directly upstream from the start codon was analyzed and two introns were found in the 5' untranslated region (UTR) of the cDNA sequence. The transcriptional initiation site was determined by 5' rapid amplification of cDNA ends (RACE), primer extension and RNase protection analysis with cerebellar RNA. Two major transcriptional initiation sites were found at position 1040 (tsp1) and -856 (tsp2) relative to the translational initiation site. Like a number of other promoters of G-protein-coupled receptors, the rSSTR3 gene lacks TATA and CAAT motifs and includes G+C-rich regions. Functional analysis of the promoter region by transfecting rSSTR3 luciferase-reporter gene constructs into rat pituitary GH3 cells and HEK 293 cells indicated that a 107-bp region upstream of tsp2 was sufficient to drive transcription. Furthermore a 562-bp region at position -1304 to -1865 upstream of the ATG start codon exerted a negative regulatory effect on transcriptional activity.

Teleost isotocin receptor: structure, functional expression, mRNA distribution and phylogeny.

A cDNA encoding a receptor for the oxytocin-related peptide isotocin has been identified by screening a lambda gt11 library constructed from poly(A)+ RNA of the hypothalamic region of the teleost Catostomus commersoni. The probe used was obtained by PCR amplification of white sucker genomic DNA using degenerate primers based on conserved sequences in the mammalian receptor counterparts. The full-length cDNA specifies a polypeptide of 390 amino acid residues that displays the typical hydrophobicity profile of a seven transmembrane domain receptor and which exhibits greatest similarity to mammalian oxytocin receptors. Oocytes that express the cloned receptor respond to the application of isotocin by an induction of membrane chloride currents indicating that it is coupled to the inositol phosphate/calcium pathway. The isotocin receptor (ITR) can also be activated by vasotocin, mesotocin, oxytocin and Arg-vasopressin, although these have lower potencies than isotocin. ITR-encoding mRNA has been detected in brain, intestine, bladder, skeletal muscle, lateral line, gills and kidney indicating that this receptor may mediate a variety of physiological functions.

Postoperative course of S-100B protein and neuron-specific enolase in patients after implantation of continuous and pulsatile flow LVADs.

BACKGROUND: In the early post-operative period after implantation of a continuous flow left ventricular assist device (LVAD) a non-pulsatile flow occurs. We compared the post-operative time-courses of protein S-100B (S100B) and neuron-specific enolase (NSE) as biochemical markers of brain injury in patients after implantation of a continuous flow LVAD and patients receiving a pulsatile flow LVAD. METHODS: Since 1998 the continuous flow DeBakey VAD has been implanted in 8 patients at our institution. For comparison purposes, a group of 7 consecutive patients in whom a pulsatile Novacor N100 LVAD was implanted were investigated. In both groups cardiopulmonary bypass (CPB) with cardiotomy suction was used. S100B and NSE were measured in serum pre-operatively, 4 hours after CPB, and on days 1, 3, 7, and 14 after implantation of the LVAD. A neurologic examination was performed pre-operatively and post-operatively on days 3 and 14. RESULTS: No differences were found between groups in pre-operative characteristics. The analysis of variance with repeated measurements for S-100B and NSE showed significant time effects (p = 0.004, p = 0.009, respectively) but no group effects (p = 0.06, p = 0.26, respectively) and no interaction between groups and time (p = 0.12, p = 0.48, respectively). The pre-operative serum level of S100B was significantly higher (p = 0.03) in the DeBakey VAD group. The pre-operative serum level of NSE was similar in the 2 groups (p = 0.7). In both groups there was a significant increase of S100B and NSE immediately after surgery (S100B: p = 0.006, p = 0.019; NSE: p = 0.01, p = 0.001). The values returned to pre-operative levels in the DeBakey VAD group on day 1 after implantation and in the Novacor group for S100B on day 3 and NSE on day 1. Post-operatively the mean values of S100B and NSE in the DeBakey VAD group compared with the Novacor group were significantly elevated only on day 3 (p = 0.005, p = 0.023).No neurologic complications were noted in patients with a continuous flow LVAD, whereas in the pulsatile LVAD group 2 patients presented neurologic abnormalities during the study period. CONCLUSIONS: The similar course of biochemical markers of brain damage in both groups may indicate that the non-pulsatile flow in the early post-operative period does not lead to increased brain injury or permeability of the brain blood barrier.Elevated levels of S100B and NSE in the post-operative period can be used as diagnostic markers of brain injury in patients after implantation of both types of LVAD.

Decision-making in end-stage coronary artery disease: revascularization or heart transplantation?

BACKGROUND: Left ventricular function is the most important predictor of survival in patients with coronary artery disease. It is also an important indicator for hospital and late mortality after operation for endstage coronary artery disease. METHODS: Between April 1986 and December 1994, 514 patients with end-stage coronary artery disease and left ventricular ejection fraction between 0.10 and 0.30 underwent coronary artery bypass grafting at the German Heart Institute Berlin. Two hundred twenty-five of these patients had been referred as possible candidates for heart transplantation. The prime criterion for bypass grafting was ischemia diagnosed by myocardial scintigraphy and echocardiography ("hibernating myocardium"). RESULTS: Operative mortality for the group was 7.1%. The actuarial survival rate was 90.8% after 2 years, 87.6% after 4, and 78.9% after 6. Left heart catheterizations performed 1 year after the operation showed that left ventricular ejection fraction had increased from a mean of 0.24 +/- 0.03 preoperatively to 0.39 +/- 0.06 postoperatively (p < 0.0001). Preoperatively 91.6% of the patients were in New York Heart Association (NYHA) class III or IV; 6 months postoperatively 90.2% of the surviving patients were in NYHA class I or II. Two hundred thirty-one patients with end-stage coronary artery disease and predominant heart failure underwent heart transplantation. Their actuarial survival rate was 74.9% after 2 years, 73.2% after 4, and 68.9% after 6. All of the patients could be recategorized into NYHA class I or II after the operation. CONCLUSIONS: We conclude that coronary artery bypass grafting and heart transplantation can be used successfully to improve the life expectancy of patients with end-stage coronary artery disease. Coronary artery bypass grafting leads to an excellent prognosis for these high-risk patients when the myocardium is preoperatively identified as being viable.

Mitral valve reconstruction and replacement for ischemic mitral insufficiency: seven years' follow up.

BACKGROUND AND AIMS OF THE STUDY: Patients with ischemic mitral incompetence have a high operative risk whether the valve is repaired or replaced. The advantage of repair over replacement is unclear in this subgroup of patients. METHODS: Between April 1986 and December 1998, 337 patients underwent surgery for ischemic mitral valve insufficiency. Coronary artery bypass grafting (CABG) was carried out concomitantly in 314 cases (93.2%). Valve repair was performed in 140 patients (operative mortality rate 12.1%). The surgical risk in patients with a left ventricular ejection fraction (LVEF) of 10-30% was higher (operative mortality rate 33.3%) than in those with LVEF >30% (operative mortality rate 8.4%). Actuarial survival rates were 75.4%, 66.8% and 61.7% after 2, 5 and 7 years, respectively. Mitral valve replacement was performed in 197 patients (operative mortality rate 14.2%). The surgical risk in patients with a LVEF of 10-30% (operative mortality rate 30.3%) was greater than in those with a LVEF of >30% (operative mortality rate 11.0%).Actuarial survival rates after replacement were 78.6%, 73.4% 67.2% after 2, 5 and 7 years, respectively. RESULTS: Our initial analysis showed that, after mitral valve repair, mortality during follow up was greater in patients with residual mitral valve insufficiency of more than grade I. Subsequent outcome was superior when repair was evaluated perioperatively with transesophageal echocardiography. When mitral insufficiency was persistently more than grade I after repair, mitral replacement was performed. A total of 105 patients was analyzed with no or maximum grade I mitral insufficiency following valve repair; actuarial survival rates were 81%, 78.4% and 77.2% after 2, 5 and 7 years' follow up. CONCLUSIONS: Patients with highly impaired LV function and ischemic mitral insufficiency are at high risk during valve repair or replacement, and cardiac transplantation should be considered for this group. However, patients with ischemic mitral insufficiency and moderately impaired LV function can undergo valve repair or replacement with an acceptable prognosis. The goal of mitral valve repair should be to reduce valvular insufficiency to at least grade I. If this is not the case, then the prognosis of repair is worse than after valve replacement. Thus, the surgeon should replace the valve during the same operation.

[Lymphographic and clinical studies following arterial reconstruction in the aortoiliac area and the extremities]. / Lymphographische und klinische Untersuchungen nach arteriellen Rekonstruktionen im aortoiliakalen Abschnitt und im Extremitätenbereich.

Lymphography was carried out in 41 patients after arterial reconstruction in the aorto-iliac territory or in the extremities: 13 of these patients had been examined pre-operatively. In addition to lymphography, the circumference of the limbs was measured. Lymphographic changes and oedema could be demonstrated in all patients, the extent depending on the type of surgical intervention. There was correlation between the extent of lymphatic damage and the oedema. The duration of post operative oedema depended on effective regeneration of the lymphatics; according to the severity of the surgical injury, regeneration was largely complete from 12 weeks to six months after surgery.

Blood flow in the internal mammary artery after the administration of papaverine during coronary artery bypass grafting.

Between January 1993 and February 1994, 106 patients whose internal mammary arteries were to be used for revascularization to treat coronary artery disease were examined for a prospective study of papaverine administration. The mean blood flow in the internal mammary artery was 59.9 mL/min +/- 7.3 mL/min before papaverine administration. The patients were divided into 3 groups: in Group I papaverine was administered intraluminally, retrograde in the internal mammary artery; in Group II, it was administered topically; and in Group III, it was administered perivascularly, in the pedicle. After papaverine administration, the mean blood flow in Group I was 135.7 mL/min +/- 10.1 mL/min; in Group II, it was 84.8 mL/min +/- 8.3 mL/min; and in Group III, it was 136.3 mL/min +/- 9.7 mL/min. The highest increases in blood flow were observed in Group I (105.3%) and in Group III (112.6%). On the basis of our results, we recommend that papaverine be injected perivascularly into the pedicle of the internal mammary artery, since retrograde injection can cause dissection.

In vitro cross-reactivity of danaparoid sodium in patients with heparin-induced thrombocytopenia type II undergoing cardiovascular surgery.

STUDY OBJECTIVES: To assess the cross-reactivity of danaparoid sodium in patients undergoing cardiovascular surgery. DESIGN: Prospective investigation. SETTING: A major European heart center and university hospital. PATIENTS: 81 patients who underwent cardiovascular surgery during the period between January 1998 and April 1999 and were diagnosed with heparin-induced thrombocytopenia (HIT) II. INTERVENTIONS: Testing was performed in patients who revealed a decrease in the platelet count >30% or a platelet count <100,000/microL during heparin therapy. Testing for HIT was performed by the use of the heparin-induced platelet-aggregation assay. Patients were evaluated as positive if an agglutination occurred in two of four of the 0.2 IU/mL heparin chambers. Patients were judged to be cross-reactive with danaparoid sodium when an agglutination occurred in two of four chambers that contained 0.2 IU/mL Orgaran. MEASUREMENTS AND MAIN RESULTS: 281 patients (5.4% of the patients who underwent surgery during the period of the investigation) were tested for HIT II. Of these, 81 (1.5% of the total) gave a positive heparin-induced platelet-aggregation assay and 23 (28%) revealed a cross-reactivity with danaparoid sodium. CONCLUSION: Cross-reactivity with heparin-induced platelet antibodies occurred in 28% of the patients who tested positive for heparin-platelet antibodies. In these patients, Orgaran would not have been a safe option. In patients with HIT II undergoing cardiac surgery, cross-reactivity with danaparoid sodium must be excluded before initiation of therapy with Orgaran, otherwise, or in cases of cross-reactivity, other options such as r-hirudin are preferred.

Tissue engineering of vascular conduits: fabrication of custom-made scaffolds using rapid prototyping techniques.

BACKGROUND: The technique of stereolithography, which automatically fabricates models from X-ray computed tomography or magnetic resonance imaging (MRI) data linked to computer-aided design programs, has been applied to the fabrication of scaffolds for tissue engineering. We previously reported on the application of stereolithography in scaffold fabrication of a trileaflet heart valve. In our current experiment we demonstrate a new technique for the fabrication of custom-made conduits for the potential replacement of a coarcted aortic segment. METHODS AND RESULTS: In this experiment the image data derived from a 12-year-old male patient with aortic coarctation scanned by MRI were processed by a computer-aided design program to reconstruct the aortic arch with isthmus stenosis three dimensionally. By defining the stenotic section and the adjacent normal vessel a custom-made nonstenotic descending aorta was reconstructed to replace the stenosed part. The rapid prototyping technique was used to establish stereolithographic models for fabricating biocompatible and biodegradable vascular scaffolds with the anatomic structure of the recalculated human descending aorta through a thermal processing technique. CONCLUSION: Our results suggest that the re-creation and reproduction of complex vascular structures by computer-aided design techniques may be useful to fabricate custom-made polymeric scaffolds for the tissue engineering of living vascular prostheses.

Myocardial viability assessment in patients with highly impaired left ventricular function: comparison of delayed enhancement, dobutamine stress MRI, end-diastolic wall thickness, and TI201-SPECT with functional recovery after revascularization.

This study compared different magnetic resonance imaging (MRI) methods with Tl(201) single photon emission computerized tomography (SPECT) and the "gold standard" for viability assessment, functional recovery after coronary artery bypass grafting (CABG). Twenty patients (64+/-7.3 years) with severely impaired left ventricular function (ejection fraction [EF] 28.6+/-8.7%) underwent MRI and SPECT before and 6 months after CABG. Wall-motion abnormalities were assessed by stress cine MRI using low-dose dobutamine. A segment with a nonreversible defect in Tl(201)-SPECT and a delayed enhancement (DE) in an area >50% of the entire segment, as well as an end-diastolic wall thickness <6 mm, was defined as nonviable. The mean postoperative EF (n=20) improved slightly from 28.6+/-8.7% to 32.2+/-12.4% (not significant). Using the Tl(201)-SPECT as the reference method, end-diastolic wall thickness, MRI-DE, and stress MRI showed high sensitivity of 94%, 93%, and 84%, respectively, but low specificities. Using the recovery of contractile function 6 months after CABG as the gold standard, MRI-DE showed an even higher sensitivity of 99%, end-diastolic wall thickness 96%, stress MRI 88%, and Tl(201)-SPECT 86%. MRI-DE showed advantages compared with the widely used Tl(201)-SPECT and all other MRI methods for predicting myocardial recovery after CABG.

[Our urologic heritage. Eugen Joseph (1879-1933)]. / Das urologische Erbe. Eugen Joseph (1879-1933).

We remember the urologist Eugen Joseph (1879-1933), working in Berlin. After a short description of his life from his extensive scientific work particularly the chromocystoscopy, the chemocoagulation of the tumours of the urinary bladder and the medical technological studies are emphasized, by which he considerably influenced the development of urology in Germany.

[Our urologic heritage: Carl Posner (1854-1928)]. / Das urologische Erbe: Carl Posner (1854-1928).

We remember the Berlin urologist Carl Posner (1854-1928) who by his scientific urological work as well as by his activities as an editor has greatly furthered the development of urology to a scientific subject. After the description of his life particularly his political work in associations is treated, which made him the organizer of the international medical associations in the first half of the 20th century.

[Our urologic heritage: Leopold Casper (1859-1959)]. / Das urologische Erbe: Leopold Casper (1859-1959).

It is reminded of the outstanding Berlin urologist Leopold Casper (1859-1959), whose work reflects half a century of the history of Berlin urology. As founder of the ureteral catheterisation and the functional renal diagnostics he helped the urology, for the recognition of which as an undependent subject he fought a life-long struggle, to further reputation.

[Philipp B. Bozzini (1773-1809). On the 175th anniversary of the death of the founder of urologic endoscopy]. / Philipp B. Bozzini (1773-1809). Zum 175. Todestag des Begründers der urologischen Endoskopie.

On the occasion of the 175th anniversary of his death we think of the physician Phillipp B. Bozzini (1773-1809), born in Frankfurt/Main, who by his light conductor, constructed in 1806, started the development of the endoscopic diagnostics. After description of his short life and an explanation of the light conductor Bozzini's merit is emphasized, by his invention as first physician to have made accessible to medicine endoscopic diagnostic possibilities.