The minimally invasive MitraClip™ procedure for mitral regurgitation under general anaesthesia: immediate effects on the pulmonary circulation and right ventricular function.

A relatively new minimally invasive cardiological procedure, called the MitraClip(™), does not require sternotomy and may have a number of advantages compared with open mitral valve surgery, but its acute impact on the pulmonary circulation and right ventricular function during general anaesthesia is unclear. We prospectively assessed the effects of the MitraClip procedure in 81 patients with or without pulmonary hypertension (defined as mean pulmonary artery pressure > 25 mmHg), who were anaesthetised using fentanyl (5 µg.kg(-1)), etomidate (0.2-0.3 mg.kg(-1)), rocuronium (0.5-0.6 mg.kg(-1)) and isoflurane. Placement of the MitraClip led to a 60% increase in mean (SD) right ventricular stroke work index (from 512 (321) to 820 (470) mmHg.ml.m(-2), p < 0.0001), while mean (SD) pulmonary vascular resistance index decreased by 24% (522 (330) to 399 (244) dyn.s.cm(-5), p < 0.0001), and mean (SD) pulmonary artery pressure decreased by 10% (30 (8) to 27 (8) mmHg, p < 0.0001). Patients with pulmonary hypertension experienced a similar decrease in mean pulmonary artery pressure compared with those without, and they also had a slight reduction in mean (SD) pulmonary artery occlusion pressure (22 (6) down to 20 (6) mmHg, p = 0.044). We conclude that successful MitraClip treatment for mitral regurgitation acutely improves right ventricular performance by reducing right ventricular afterload, regardless of whether patients have pre-operative pulmonary hypertension.

Myocardial protection by remote ischaemic pre-conditioning is abolished in sulphonylurea-treated diabetics undergoing coronary revascularisation.

BACKGROUND: Remote ischaemic pre-conditioning attenuates myocardial injury. Because sulphonylurea drugs interfere with ischaemic and anaesthetic pre-conditioning, we assessed whether remote ischaemic pre-conditioning effects are altered in sulphonylurea-treated diabetics. METHODS: Using the database of our ongoing randomised, placebo-controlled study (ClinicalTrials.gov NCT01406678), we assessed the troponin I concentration area under curve (measurements: baseline, 1, 6, 12, 24, 48, and 72 h post-operatively) in sulphonylurea-treated diabetics (n = 27) and non-diabetics (n = 230) without and with remote ischaemic pre-conditioning (three 5-min periods of left upper arm ischaemia with 5-min reperfusion each) during isoflurane anaesthesia before two- to three-vessel coronary artery surgery. RESULTS: Remote ischaemic pre-conditioning in non-diabetic patients evoked a 41% decrease in the troponin I concentration area under curve (514 ng/ml × 72 h ± 600 vs. 302 ± 190, P = 0.001) but no change (404 ng/ml × 72 h ± 224 vs. 471 ± 383, P = 0.62) in sulphonylurea-treated diabetics. There was no significant correlation between the troponin I concentration area under curve and arterial glucose concentrations, and the latter was not an independent confounder. CONCLUSION: Cardioprotection by remote ischaemic pre-conditioning during isoflurane anaesthesia is abolished in sulphonylurea-treated diabetics.

Arrhythmogenic risk of pulmonary artery catheterisation in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

Many clinicians consider severe aortic stenosis to be a contraindication to pulmonary artery catheterisation, except during open heart surgery with cardiopulmonary bypass. This is due to the perceived high risk of arrhythmia, although the true incidence of ventricular tachycardia and fibrillation remains unclear. We conducted a retrospective study to estimate the incidence of severe arrhythmias during pulmonary artery catheterisation in 380 patients with severe aortic stenosis scheduled for transcatheter aortic valve implantation. Ventricular fibrillation was seen in only one patient (0.26%), and this was successfully terminated by external defibrillation. No episodes of ventricular tachycardia were recorded and there were also no arrhythmias during removal of the catheter. We have therefore concluded that pulmonary artery catheterisation in patients with severe aortic stenosis is not associated with a high incidence of ventricular fibrillation or tachycardia, allowing pulmonary artery pressure monitoring to be performed relatively safely in such patients.

Early thromboelastometric variables reliably predict maximum clot firmness in patients undergoing cardiac surgery: a step towards earlier decision making.

BACKGROUND: While much effort has been spent on guiding coagulation and transfusion therapy in patients undergoing cardiopulmonary bypass (CPB) surgery, the use of conventional laboratory-based coagulation tests is hampered by long turnaround times and interference with heparin and protamine. To allow faster assessment of maximum clot firmness (MCF) by point-of-care thromboelastometry (ROTEM®, TEM International GmbH, Munich, Germany), we tested whether clotting time (CT), clot formation time (CFT), or early values of clot firmness (CF) predict MCF. METHODS: Results of 437 ROTEM® assays (EXTEM®, INTEM®, FIBTEM®, and HEPTEM®) from 84 patients undergoing CPB surgery were analyzed. Measurements were performed prior to and after heparin administration, as well as after protamine administration and CT, CFT, and CF after 5, 10, and 15 min (A5, A10, and A15) after initial clotting (CT) were related to MCF. STATISTICS: Regression and Bland-Altman analyses and receiver-operating characteristics (ROCs). RESULTS: CFT (r = 0.87-0.95), A5 (r = 0.84-0.98; P < 0.0001), A10 (r = 0.86-0.98; P < 0.0001), and A15 (r = 0.86-0.98; P < 0.0001) demonstrated high correlation coefficients with MCF, whereas CT correlated weakly (r = 0.07-0.41). As expected, correlation coefficients increased with the time allowed to assess a specific variable. ROC analyses demonstrated excellent accuracy for CFT, A5, A10, and A15 [area under the curve (AUC): 0.9476-0.9931] to predict a subnormal MCF, whereas CT demonstrated poor accuracy (AUC: 0.5796-0.6774). CONCLUSION: Taking into account specific bias, early values of CF (A5-A15) reliably predict maximum CF under all conditions and, therefore, allow for marked time savings in the interpretation of ROTEM® measurements. This may guide earlier and more specific treatment of CPB-related coagulation disorders.

Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol - a clinical trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) of the myocardium by limb ischemia/reperfusion may mitigate cardiac damage, but its interaction with the anesthetic regimen is unknown. We tested whether RIPC is associated with differential effects depending on background anesthesia. Specifically, we hypothesized that RIPC during isoflurane anesthesia attenuates myocardial injury in patients undergoing coronary artery bypass graft (CABG) surgery, and that effects may be different during propofol anesthesia. METHODS: In a randomized, single-blinded, placebo-controlled prospective study, serum troponin I concentration (cTnI) (baseline, and 1, 6, 12, 24, 48, and 72 h postoperatively) were measured during isoflurane/sufentanil or propofol/sufentanil anesthesia with or without RIPC (three 5-min periods of intermittent left upper arm ischemia with 5 min reperfusion each) in non-diabetic patients (n = 72) with three-vessel coronary artery disease (ClinicalTrials.gov NCT01406678). RESULTS: RIPC during isoflurane anesthesia (n = 20) decreased the area under the cTnI time curve (cTnI AUC) (-50%, 190 ± 105 ng/ml × 72 h vs. 383 ± 262 ng/ml × 72 h, P = 0.004), and the peak (7.3 ± 3.6 ng/ml vs. 11.8 ± 5.5, P = 0.004) and serial (P < 0.041) postoperative cTnI when compared to isoflurane alone (n = 19). In contrast, RIPC during propofol anesthesia (n = 14) did not alter the cTnI AUC [263 ± 157 ng/ml × 72 h vs. 372 ± 376 ng/ml × 72 h (n = 19), P = 0.318] or peak postoperative cTnI (10.1 ± 4.5 ng/ml vs. 12 ± 8.2, P = 0.444). None of the patients experienced harm or side effects from the intermittent left arm ischemia. CONCLUSION: Thus, RIPC during isoflurane but not during propofol anesthesia decreased myocardial damage in patients undergoing CABG surgery. Accordingly, effects of RIPC evoked by upper limb ischemia/reperfusion depend on background anesthesia, with combined RIPC/isoflurane exerting greater beneficial effects under conditions studied.

Genetic interactions in the ß-adrenoceptor/G-protein signal transduction pathway and survival after coronary artery bypass grafting: a pilot study.

BACKGROUND: In heart failure, ß-adrenergic receptor (ßAR) stimulation desensitizes the receptor, uncouples the downstream Gαs protein, and diminishes signal transduction. We tested the hypotheses that haplotype-tagging single-nucleotide polymorphisms (htSNPs) within the Gαs gene (GNAS) (i) are functionally active and alter Gαs expression, (ii) influence survival after coronary artery bypass grafting (CABG), and (iii) interact with ßAR SNPs. METHODS: Amplification of GNAS intron 1 was followed by cloning, reporter assays, electrophoretic mobility shift assays, and western blots. In a pilot study, 185 patients on ßAR blockade undergoing CABG were studied prospectively. The primary endpoint was cardiac-related mortality at 1 yr. RESULTS: Two htSNPs defined three common haplotypes with altered reporter activity, allele-specific transcription factor binding, and Gαs protein expression (highest in *3 carriers followed by *2 and *1 haplotypes, P=0.013). After CABG, mortality was GNAS diplotype-dependent: *3/*3: 0%; *3/*2: 2.4%; *3/*1: 2.9%; *2/*2: 4.5%; *2/*1: 9.1%; and *1/*1: 20.0% (P=0.004). While ß(1)AR SNPs were not associated with mortality, ß(2)AR Arg16 allele carriers were at higher risk than Gly16 allele carriers (P=0.008). Gene-gene interaction using gene-related risk alleles demonstrated the number of risk alleles to be independently associated with death (hazard ratio 2.3; 95% confidence interval: 1.5-3.5; P=0.0003). Carriers of the no-risk allele had higher maximum isoproterenol-stimulated adenylyl cyclase activities than risk allele carriers (P=0.003). CONCLUSIONS: Interactions in the ßAR/Gαs pathway may be associated with altered mortality after CABG. This could reconcile previously inconclusive data regarding the effects of ßAR SNPs on cardiovascular prognosis.

Transfemoral aortic valve implantation under sedation and monitored anaesthetic care--a feasibility study.

Surgical aortic valve replacement is the conventional treatment for symptomatic aortic valve stenosis; however, the technique of transfemoral transcatheter aortic valve implantation has recently been developed for older patients at high risk for surgery. We assessed whether this procedure could be safely performed under sedation in 100 patients. Their predicted surgical mortality was 21.6% and mean (SD) age 80 (6.6) years. Sedation was provided by remifentanil infusion (0-0.2 µg.kg(-1).min(-1)) and midazolam (1-3 mg), as required. All patients were closely haemodynamically monitored throughout by an anaesthetist and inotropic drugs administered as indicated by invasive monitoring. Sedation alone was required in 83 patients; in 17 patients sedation had to be converted to general anaesthesia, mainly because of interventional complications (n = 12). All conversions to general anaesthesia occurred after successful valve implantation. Mean (SD) anaesthesia time was 31 (12) min and procedural time 107 (77) min; 30-day and 1-year all-cause mortality were 6% and 13%, respectively. In the majority of patients, transcatheter valve implantation can safely be facilitated by sedation, provided monitoring and drug administration are carried out by an experienced cardiac anaesthetist.

[Hybrid room technology as a prerequisite for the modern therapy of aortic dissection]. / Hybridraumtechnologie als Voraussetzung für die moderne Therapie der Aortendissektion.

With the establishment of a hybrid room 7 years ago, it was possible for the first time to unite a full range of diagnostics and surgical therapy under the sterile conditions of an operating theatre in life-threatening aortic dissection. Thus, the early phase associated with high mortality rates (3%-5% per hour) could be significantly reduced from 8 h to 4 h. Multidisciplinary teams consisting of a cardiac surgeon, a cardiologist and an anaesthetist enable competent and rapid life-saving measures. In the case of acute and persistent visceral and/or peripheral malperfusion over many hours, primary endovascular reconstitution of perfusion precedes delayed surgical replacement of the ascending aorta with or without the aortic arch. Additional strategic and technical surgical developments have helped reduce overall hospital mortality from 15%-20% to 10%-15%. Though expensive to build, a high-technology hybrid room enables interdisciplinary specialization and concentration, as demonstrated by the exponential growth in the development of transcatheter aortic valve implants or the endovascular treatment of aortic disease.

[Dyspnea and chronic recurrent respiratory tract infections]. / Dyspnoe und rezidivierende Atemwegsinfekte.

A 48-year-old man presented with recurrent bronchopulmonary infections of many years' standing. The diagnosis of tracheobronchomegaly (Mounier-Kuhn syndrome) was based on CT examination and subsequent bronchoscopy. Since lung transplantation was not considered advisable, a biluminal stent was inserted to prevent bronchial collapse.

Impairment of endothelium-dependent vasorelaxation in experimental atherosclerosis is dependent on gender.

OBJECTIVE: Nitric oxide (NO) has been suggested to have antiatherosclerotic effects. It has also been demonstrated that there is a greater basal release of endothelium derived relaxing factor (EDRF) in female as compared to male rabbit aorta, which also might have beneficial effects in atherosclerosis. We thus sought to determine if gender influences the severity of atherosclerosis. METHODS: We studied 18 female and 18 male New Zealand White rabbits that were randomly divided in two groups of 9 animals each and fed either a standard or a cholesterol diet (0.75%) for 15 weeks. RESULTS: In cholesterol-fed rabbits the percentage of atherosclerotic lesions in the aorta was identical in females and males and was inversely correlated with the maximal aortic relaxation to acetylcholine as assessed in organ chamber experiments (females: P < 0.0008, males: P < 0.0002). Importantly, the cholesterol diet induced a significantly (P < 0.025) more severe impairment of maximal vasorelaxation to acetylcholine in males from 78.4 +/- 1.2% to 29.4 +/- 10.2%) compared to females (from 84.4 +/- 1.2% to 60.7 +/- 8.5%). Both male gender (P < 0.0001) and the extent of impairment of endothelium-dependent relaxation (P < 0.0002) were associated with a reduced aortic sensitivity to S-nitroso-N-acetyl-D,L-penicillamine, which releases NO into the organ bath. In contrast, the aortic sensitivity to the organic nitrates pentaerythritol tetranitrate and isosorbide 5-nitrate, which release NO after enzymatic metabolization within the smooth muscle, was not reduced. CONCLUSIONS: These results suggest that the impairment of endothelium-dependent vasorelaxation induced by atherosclerosis is dependent on gender. This may be due to a greater degradation of extracellular NO in the vessel wall of males.

In vivo effects of pentaerythrityl-tetranitrate and isosorbide-5-mononitrate on the development of atherosclerosis and endothelial dysfunction in cholesterol-fed rabbits.

We wished to determine whether long-term treatment with organic nitrovasodilators has pharmacological effects on the development of atherosclerotic lesions and endothelial dysfunction in cholesterol-fed rabbits. For 15 weeks, six groups of 9 New Zealand White rabbits received a standard diet, which contained no admixture, pentaerythrityl-tetranitrate (PETN 6 mg/kg body weight/day), or isosorbide-5-mononitrate (ISMN 2 mg/kg body weight/day). In the other three groups, the same diets were further enriched with cholesterol (0,75%). Four rings of thoracic aorta were used for tension studies; these rings and the aortas from the aortic arch to bifurcation were then fixed in formol and stained with Sudan IV to determine the area of luminal atherosclerotic lesions by a computerized laser-scanning approach. The cholesterol diet increased plasma levels of cholesterol from 69.8 +/- 10.4 to 907.1 +/- 85.5 mg/dl. A similar result was obtained in the group receiving PETN/cholesterol, but the group fed ISMN/cholesterol showed a significantly higher plasma level of cholesterol (1,165 +/- 81.4 mg/dl). Plasma levels of PETN metabolites were still detectable by gas chromatography/mass spectrometry after a 24-h in vivo washout period. The cholesterol diet induced a pronounced degree of atherosclerotic lesions in the aortic arch and the thoracic and abdominal aorta: 73.3 +/- 1.9, 46.3 +/- 2.5, and 49.6 +/- 3.6%, respectively. Additional treatment with PETN resulted in a reduction of this atherosclerotic area to 58.6 +/- 2.05% (p < 0.0001), 34.7 +/- 1.98% (p < 0.01), and 39.3 +/- 3.06% (p < 0.05). In contrast, ISMN had no significant effect on this parameter. The cholesterol diet also induced an endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine (ACh). Treatment with PETN completely inhibited the development of endothelial dysfunction, whereas ISMN had no effect. In the three groups receiving a cholesterol diet, an increased extent of aortic lesions significantly correlated with increased endothelial dysfunction measured in the same preparations. The long-term treatment with PETN did not affect the vasorelaxing potency of PETN in aortic rings, and similar results were obtained in the case of ISMN. We conclude that long-term treatment with doses of PETN, which do not promote the development of in vitro vascular nitrate tolerance, may protect against atherosclerosis and endothelial dysfunction. This novel, yet unknown pharmacodynamic quality of nitrovasodilators like PETN may contribute to their long-term efficacy in coronary artery disease but may also imply new therapeutic indications in the future.