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).

[Certification in cardiology : Contra: The concept should be improved]. / Zertifizierungen in der Kardiologie : Kontra: Das Konzept sollte verbessert werden.

Increasing complexity and new highly differentiated therapeutic procedures in cardiology result in a need for additional training beyond cardiology board certification. The German Cardiac Society therefore developed a variety of certifications of educational curricula and definition of specialized centers. Standardization and structuring in education and patient treatment, as defined by certifications may be helpful; however, introduction of certification can have serious consequences for hospital structure, the side effects of which may impair quality of treatment for individual patients. The current article discusses these issues against the background of the following questions: how is quality defined? How do certifications interfere with patient care on a nationwide level, how do they influence responsibilities and teamwork? Are there conflicts of interests by designing certifications and how good are the organizational structures? Finally, suggestions are made on what has to be considered when designing certifications. Certifications should acknowledge all cardiologists, irrespective of their position in the level of care. There should be a coherent unified concept synchronizing all certifications and administration needs to be transparent and well structured.

[Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR) : Consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC]. / Empfehlungen zur extrakorporalen kardiopulmonalen Reanimation (eCPR) : Konsensuspapier der DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI und GRC.

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible etiology. Currently there are no randomized, controlled studies on eCPR, and valid predictors of benefit and outcome which might guide the indication for eCPR are lacking. Currently selection criteria and procedures differ across hospitals and standardized algorithms are lacking. Based on expert opinion, the present consensus statement provides a proposal for a standardized treatment algorithm for eCPR.

[Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR) : Consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC]. / Empfehlungen zur extrakorporalen kardiopulmonalen Reanimation (eCPR) : Konsensuspapier der DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI und GRC.

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible etiology. Currently there are no randomized, controlled studies on eCPR, and valid predictors of benefit and outcome which might guide the indication for eCPR are lacking. Currently selection criteria and procedures differ across hospitals and standardized algorithms are lacking. Based on expert opinion, the present consensus statement provides a proposal for a standardized treatment algorithm for eCPR.

[Hemorrhage under direct oral anticoagulants : Occurrence and treatment in intensive care patients]. / Blutungen unter direkten oralen Antikoagulanzien : Auftreten und Therapie bei Intensivpatienten.

The use of anticoagulants is associated with an increased risk of bleeding and nevertheless bleeding complications can be lifethreatening. The focus is on bleeding under direct oral anticoagulants (DOAC) because antidotes and specific measures are lacking for some DOACs. Furthermore, routinely carried out clotting tests cannot be used to determine the degree of anticoagulation under DOACs. Therefore, it becomes difficult to determine whether the coagulation inhibition effect is present. This article presents the treatment of hemorrhage in patients with DOACs in the intensive care unit. Further, the indications for DOACS and details of administration and monitoring are presented.

[Management of NOAK administration during invasive or surgical interventions : When and how to pause and when to restart?] / Steuerung der NOAK-Gabe bei invasiven oder operativen Interventionen : Wann bzw. wie pausieren und wann wieder starten?

Many patients under oral anticoagulation therapy need percutaneous or surgical interventions/operations. For vitamin K antagonists (VKA), there are recommendations regarding preoperative or postoperative administration. Management of the new oral anticoagulants (NOAC) was supposed to be easier - but some aspects must be considered. Due to the different pharmacokinetic profiles of substances such as dabigatran, rivaroxaban, apixaban, and edoxaban, different recommendations are given.Upon periprocedural management, thromboembolic risk has to be considered in patients treated with NOACs. NOACS have a pharmacokinetic advantage in terms of a rapid onset and rapid elimination via the liver and kidneys. Impaired renal function results in extended half-life of NOACs considerably.Surgical procedures under NOACS can be scheduled at the beginning of next dosing interval or omitted in low/minimal bleeding risk patients, so that only 2-3 NOAC doses are not administered. In patients with moderate and high risk of bleeding, there should be a NOAC break of 24-48 h prior to surgery in order to allow a corresponding decay of the active metabolite. In patients with low/intermediate risk for thromboembolism, no bridging is necessary if the "unprotected" time (NOAC break) is less than 4-5-(7) days. In patients at high risk of thromboembolism, individual consideration must be taken regarding bridging or extended NOAC break. Whether NOACs can be dispensed or bridging is necessary in these patients must be clarified in randomized trials for periprocedural management of NOACs patients.

Effect of ACE inhibition on the fibrinolytic system in patients requiring coronary artery bypass grafting.

BACKGROUND: Regulation of the fibrinolytic balance between plasminogen activators and inhibitors is modulated by the renin-angiotensin system. Thus, alterations in the renin-angiotensin system by ACE inhibitors probably result in modification of the fibrinolytic system. We examined the effect of a short-term treatment with the ACE inhibitor enalapril in 47 patients with severe coronary artery disease requiring coronary artery bypass grafting (CABG). METHODS: Patients received either 20 mg/d enalapril or placebo for 6 days. Tissue-type plasminogen activator (TPA), plasminogen activator inhibitor-1 (PAI-1), plasmin-a2-antiplasmin-complex (PAP) and D-dimers were measured initially and after treatment. RESULTS: In the enalapril group PAI-1 levels were significantly reduced after treatment (11.9 +/- 2.3 U/ml vs. 17.1 +/- 3.0 U/l; P < 0.05). In the placebo group PAP levels were significantly higher ( P < 0.05) after treatment compared to initial values. No differences could be detected between the study groups with regard to TPA and D-dimers. CONCLUSION: Although PAI-1 activity levels are reduced after short-term treatment with ACE inhibitors in patients with stable angina pectoris while TPA antigen is unaffected, treatment with ACE inhibitors does not lead to a marked change in plasmin activation.

Aortic insufficiency due to a partial left-coronary aortic valve prolapse and the detection of two small interatrial jets after blunt thoracic trauma.

Aortic valve regurgitation due to blunt thoracic trauma is a rare complication. Autopsy studies have been shown that the aortic valve is the most often lacerated one among the heart valves. Actually, we describe a case of a 47 year old man with the signs of heart failure after a blunt thoracic trauma 2 months before caused by aortic insufficiency due to a partial left-coronary aortic valve prolapse. Furthermore, transthoracic and transesophageal echocardiography revealed two small jets between the left and the right atrium.

Increased fibrin specificity and reduced paradoxical thrombin activation of the combined thrombolytic regimen with reteplase and abciximab versus standard reteplase thrombolysis.

In patients with acute myocardial infarction treated with thrombolytics, platelet activation as well as alterations of the hemostatic and fibrinolytic systems have been described favoring early infarct-related artery reocclusion. We investigated the effects of a newer thrombolytic regimen with half-dose double-bolus reteplase (2 x 5 IU, 20 patients) combined with abciximab versus full-dose reteplase (2 x 10 IU, 18 patients) on the fibrinolytic and the hemostatic system in patients with acute ST-segment elevation (in the electrocardiogram) myocardial infarction. The thrombolytic regimen with half-dose reteplase in combination with abciximab caused in vivo a lower systemic plasminemia and a lower paradoxical activation of the contact phase of the coagulation system (measured as activated factor XII); a lower paradoxical thrombin activation/generation; and a lesser extent of fibrinogen breakdown compared with the reteplase regimen. These results could be, at least in part, a possible explanation for the observed significantly lower rates of reinfarction until 7 days after enrollment and of recurrent ischemia in the combination group in the Global Use of Strategies to Open Occluded Coronary Arteries V (GUSTO V) trial.

Insulin-like effect of low-dose leptin on glucose transport in Langendorff rat hearts.

BACKGROUND: In a murine myotube cell line (C 2 C 12 myotubes), leptin at low physiological concentrations (1 ng/ml) has been shown to stimulate glucose transport and glycogen synthesis. The aim of the present study was to test whether an analogous leptin effect on glucose transport is detectable in the heart. METHODS AND RESULTS: We used the isolated Langendorff rat heart preparation with hemodynamic function control. Using polymerase chain reaction (RT-PCR), a 346- and 375-base fragment indicative for the short and long leptin receptor isoform was detected in the rat heart. Glucose transport rates were calculated using equimolar double tracer perfusion with the non-metabolizable glucose analog 3-O-methylglucose (3-O-MG) and the non-transportable tracer mannitol and two-compartimental modeling. 3-O-MG uptake at a perfusate glucose concentration of 11 mM was measured over 15 minutes in control hearts, hearts perfused with insulin (10 mU/ml), leptin (1 ng/ml) or insulin (10 mU/ml) plus leptin (1 ng/ml; n = 8 in each group). The basal 3-O-MG transport rate of 0,7351 +/- 0,051 micro mol/min/g wet weight was increased 4.18 fold with insulin, 2.69 fold with leptin, and 4.2 fold with leptin plus insulin. Simultaneous monitoring of hemodynamic function revealed a minor and transient effect of leptin on left ventricular pressure, which was strongly augmented in coperfusion with insulin. CONCLUSIONS: The data suggest that leptin at low physiological concentrations is able to exert a partial insulin like effect on glucose uptake. We speculate that the effect might be mediated by both leptin receptor isoforms. This leptin effect is additive to the effect of insulin and might therefore contribute to the insulin independent basal glucose supply of the heart. It can not be completely excluded that the observed leptin effect on glucose transport is secondary to altered myocardial function.

Benefical effects of reteplase in combination with abciximab: platelet/leukocyte interactions and coagulation system.

Pathophysiological aspects of acute myocardial infarction include altered hemostatic and fibrinolytic systems as well as platelet activation. Treatment with thrombolytics and GP IIb/IIIa antagonists has been described as having an additional influence on these systems. We investigated the effects of a new thrombolytic regimen with half-dose double-bolus reteplase (2 x 5 IU, 20 patients) combined with abciximab versus full dose reteplase (2 x 10 IU, 18 patients) on platelet-granulocyte complexes and on thrombin-antithrombin III complexes in patients with acute ST-segment elevation myocardial infarction. In vivo, the thrombolytic regimen with half-dose reteplase in combination with abciximab caused fewer platelet-granulocyte aggregates (measured as percentage of CD41-positive granulocytes) and a lower paradoxical activation of the coagulation system (measured as thrombin-antithrombin III complex) compared with the reteplase regimen. The combination regimen could therefore have benefical effects on platelet-induced leukocyte activation and leukocyte-mediated proinflammatory/cytotoxic effects as well as on granulocyte-induced effects on endothelium, tissue damage and coagulation. This could be, at least in part, a possible explanation for the significantly lower rates of reinfarction, recurrent ischaemia and percutaneous coronary interventions observed during the early phase after an acute myocardial infarction in the combination group in the GUSTO-V trial.

Influence of ACE inhibition on myocardial damage, the Kallikrein-Kinin system and hemostasis during cardiopulmonary bypass surgery.

BACKGROUND: ACE inhibitors may have a cardioprotective effect by enhancing bradykinin levels during cardiopulmonary bypass (CPB). However, ACE inhibition could lead to unwelcome effects on the kallikrein contact phase during CPB (since reduction of kallikrein activity by aprotinin has been shown to be beneficial) and may alter the hemostasis. We examined the effects of ACE inhibitors on intraoperative myocardial damage, kallikrein contact phase and hemostasis in patients undergoing CPB. METHODS: 47 patients randomly received either 20 mg/d enalapril or placebo. Creatine kinase (CK and CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), thrombin-antithrombin III complex (TAT), fibrinogen and kallikrein-like activity were measured before surgery, during and immediately after CPB, at the end of surgery and 1, 3 and 5 days after surgery. RESULTS: No significant differences between enalapril- and placebo- treated patients concerning CK (318 +/- 38.6 U/l vs. 316 +/- 16.8 U/l), CK-MB, LDH, TnT (1.81 +/- 0.45 ng/ml vs. 1.52 +/- 0.34 ng/ml), TAT, fibrinogen and kallikrein-like-activity could be found during study period. CONCLUSIONS: Reduction of ischemic injury during CPB is not achieved with ACE inhibitors. However, treatment of patients with ACE inhibitors before and during CPB is fully feasible without side effects affecting the kallikrein contact phase or significant influence on hemostasis.

Acute gender-specific hemodynamic and inotropic effects of 17beta-estradiol on rats.

Estrogen has cardioprotective effects. In addition to beneficial effects on lipid metabolism, estrogen affects the vascular tone and may reduce endothelial dysfunction. In the present study, we examined acute gender-specific hemodynamic and inotropic effects of 17beta-estradiol (17beta-E) versus the control situation in open-chest rats. In addition to measurements in the intact circulation, myocardial function was examined on the basis of isovolumic registration independent of peripheral vascular effects. Regarding the dose-dependent and gender-specific effects of 17beta-E, in female rats, 17beta-E (50, 100, or 200 ng/kg) increased cardiac output (CO) (26%, 43%, and 59% versus control animals) as a result of reduction in total peripheral resistance (TPR) (-13%, -18%, and -24%) without any effect on myocardial contractility (isovolumic left ventricular systolic pressure, -1%, 0%, and -6%). These vascular effects are less pronounced in male rats (for 200 ng/kg 17beta-E: CO, 34%; TPR, -14%). We investigated gender-specific effects of 200 ng/kg 17beta-E after pretreatment with the estrogen receptor (ER) antagonist ICI 182,780. ER blockade reduced the effects of estrogen in female rats (CO, 29%; TPR, -17%) and male rats (CO, 19%; TPR, -11%). Regarding the effects of 200 ng/kg 17beta-E after pretreatment with N(G)-nitro-L-arginine methyl ester, NO synthesis inhibition completely prevented the acute vascular effects of estrogen in female rats (CO, -4%; TPR, 1%). In addition, immunohistochemical staining revealed no gender-specific differences of the vascular ER distribution. 17beta-E caused an acute dose-dependent and gender-specific reduction in the afterload. ERs are involved in both genders in this vasodilative effect that is mediated by NO. This NO-mediated effect may explain in part the cardioprotective effect of estrogen.

The thrombolytic paradox.

Thrombolytic drugs do not only stimulate the plasmin system but also induce thrombin activation additionally to the preexisting hypercoagulative state in patients with acute myocardial infarction. Testing the in vitro-derived hypothesis of a plasmin-mediated activation of the contact phase of the coagulation leading to the procoagulant effect, several thrombolytic regimen have been evaluated. Paradoxical thrombin activation (referred to as "thrombolytic paradox") was related to absence of fibrin specificity. Highly fibrin-specific drugs like tenecteplase did not cause additional thrombin activation, while non-fibrin-specific drugs like streptokinase caused a marked additional activation of the contact phase and of thrombin. It could be shown that the thrombolytic paradox was related to the extent of systemic plasmin activation confirming the hypothesis of a plasmin-mediated factor XII/kallikrein system activation as cause of the thrombolytic paradox.

[Atherothrombosis and inflammation]. / Atherothrombose und Inflammation.

Alterations of coagulation, fibrinolysis, platelets and low grade inflammation are causal pathophysiological factors in atherosclerosis. Considerable activation of several involved pathways occurs during the acute progression of atherosclerotic lesions, which is characterized by an occluding thrombus, and local and systemic inflammatory reactions as in patients with acute coronary syndromes. These patients become clinically compromised due to the reduction in coronary flow. Furthermore, a frequent occurrence of non-occluding thrombi may be assumed as a progression factor in atherosclerotic diseases. Both the extrinsic and the intrinsic pathway of coagulation are involved, resulting in a hypercoagulative state. Furthermore, an inflammatory acute phase reaction occurs in addition to the activation of several other inflammatory pathways in patients with unstable angina pectoris or acute myocardial infarction. Exposure of tissue factor by the ruptured plaque together with a systemic hypercoagulative state, local and systemic inflammation as well as stimulated platelets and endothelial dysfunction are involved in the pathophysiology of acute coronary syndromes. In the following paper the current knowledge on activation of these pathways and on the various complex interactions is discussed.

Percutaneous coronary interventions using a new 5 French guiding catheter: results of a prospective study.

The aim of this prospective study was to analyze the technical feasibility, the success rate, and the special complications of percutaneous coronary interventions (PCIs) using a newly released 5 Fr guiding catheter with an inner diameter of 0.058". The study was performed in 150 consecutive patients subjected to coronary angioplasty. In 89% of the patients, the intervention was started with a 5 Fr catheter (JR4 or JL4); in 16 patients a 6 or 7 Fr catheter was used because of unstable clinical conditions according to the decision of the interventional cardiologist. In 12 out of 134 patients, the guiding catheter had to be changed during the intervention from 5 Fr to a 6 or 7 Fr catheter due to poor backup support. In 112 out of 118 patients, the intervention was successfully performed using a 5 Fr catheter (95%); in 12 out of 16 patients, after changing the guiding catheter, the overall success rate was 93%. In patients with type A and B lesions who were initially treated using a 5 Fr catheter, the procedural success rate was 100% (81 out of 81), whereas in patients with type C lesions the procedural success rate was 83% (43 out of 53; P = 0.000053, Fisher's exact test). Furthermore, in patients with a diameter stenosis < 90%, the procedural success rate was 100% (57 out of 57), whereas in patients with a diameter stenosis of 90%-100%, the procedural success rate was 87% (67 out of 77; P = 0.0050). Stent implantation was performed successfully in 24 patients (18%) using the 5 Fr guiding catheter. This study confirms that PCI was technically feasible using a 5 Fr guiding catheter in the majority of consecutive patients with a success rate of 95%. There were significant differences in the success rate depending on the lesion type and the diameter stenosis. Complications were very rare and were not related to the guiding catheter. Limitations of the 5 Fr guiding catheters arose mainly from a poor backup support in long lesions and severe stenosis. Cathet Cardiovasc Intervent 2001;53:308-312.

Subacute myocardial infarction: assessment by STIR T2-weighted MR imaging in comparison to regional function.

PURPOSE: Increased T2 signal intensity (SI) can be regularly observed in myocardial infarction. However, there are controversial reports about the relationship of elevated T2 SI to myocardial viability and some authors propose that high T2 SI serves as a sign of irreversible myocardial injury. This study investigates increased T2 SI compared to myocardial function in patients with reperfused subacute myocardial infarction. Preserved function was used as criterion for viability. METHODS: Ten healthy volunteers and 17 patients with myocardial infarction and patent infarct related coronary artery were examined on a 1.5 T Magnetom Vision system (Siemens). For T2-weighted MR imaging a breath-hold STIR sequence with dark-blood preparation was used. Cine FLASH 2D imaging was applied to assess myocardial function. Signal-to-noise (S/N) in STIR T2 images was measured in normal and infarcted regions and subsequently identified by two independent observers. Based on a 20 segment model of the left ventricle findings were compared to regional myocardial function. RESULTS: Elevated STIR T2 SI was found in all 17 patients and observed in 27% (204/754) of segments. S/N of normal myocardium was 5.1 +/- 0.7 in volunteers and 4.9 +/- 0.8 in patients (P = NS). Infarcted myocardium presented with significantly increased S/N 12.8 +/- 1.9 (P < 0.0001). Significant transmural elevation of T2 SI was noted in 32% of segments with preserved systolic function. CONCLUSION: Increased STIR T2 SI can be observed transmurally in post-ischemic myocardial regions with preserved function. It therefore cannot be used as an exclusive marker for the non-viable region.