Eva Kottenberg

Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial

BACKGROUND Remote ischaemic preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We investigated the safety and efficacy of this procedure. METHODS Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were prospectively randomised to receive remote ischaemic preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia) or no ischaemic preconditioning (control). The primary endpoint was myocardial injury, as reflected by the geometric mean area under the curve (AUC) for perioperative concentrations of cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was the main safety endpoint. Analysis was done in intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT01406678. FINDINGS 329 patients were enrolled. Baseline characteristics and perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72 h (95% CI 237-298) in the remote ischaemic preconditioning group and 321 ng/mL (287-360) in the control group. In the intention-to-treat population, the ratio of remote ischaemic preconditioning to control for cTnI AUC was 0·83 (95% CI 0·70-0·97, p=0·022). cTnI release remained lower in the per-protocol analysis (0·79, 0·66-0·94, p=0·001). All-cause mortality was assessed over 1·54 (SD 1·22) years and was lower with remote ischaemic preconditioning than without (ratio 0·27, 95% CI 0·08-0·98, p=0·046). INTERPRETATION Remote ischaemic preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery. FUNDING German Research Foundation.

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

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.

Cerebral Embolization During Transcatheter Aortic Valve Implantation A Transcranial Doppler Study

Background— Transcatheter aortic valve implantation (TAVI) is associated with a higher risk of neurological events for both the transfemoral and transapical approach than surgical valve replacement. Cerebral magnetic resonance imaging has revealed more new, albeit clinically silent lesions from procedural embolization, yet the main source and predominant procedural step of emboli remain unclear. Methods and Results— Eighty-three patients underwent transfemoral (Medtronic CoreValve [MCVTF], n=32; Edwards Sapien [ESTF], n=26) and transapical (ESTA: n=25) TAVI. Serial transcranial Doppler examinations before, during, and 3 months after TAVI were used to identify high-intensity transient signals (HITS) as a surrogate for microembolization. Procedural HITS were detected in all patients, predominantly during manipulation of the calcified aortic valve while stent valves were being positioned and implanted. The balloon-expandable ES prosthesis caused significantly more HITS (mean [95% CI]) during positioning (ESTF, 259.9 [184.8–334.9]; ESTA, 206.1[162.5–249.7]; MCVTF, 78.5 [25.3–131.6]; P<0.001) and the self-expandable MCV prosthesis during implantation (MCVTF, 397.1 [302.1–492.2]; ESTF, 88.2 [70.2–106.3]; ESTA, 110.7 [82.0–139.3]; P<0.001). Overall, there were no significant differences between transfemoral and transapical TAVI or between the MCV and ES prostheses. No HITS were detected at baseline or 3-month follow-up. There was 1 major procedural stroke that resulted in death and 1 minor procedural stroke with full recovery at 3-month follow-up in the MCV group. Conclusions— Procedural HITS were detected by transcranial Doppler in all patients. Although no difference was observed between the transfemoral and the transapical approach with the balloon-expandable ES stent valve, transfemoral TAVI with the self-expandable MCV prosthesis resulted in the greatest number of HITS, predominantly during implantation.

STAT5 Activation and Cardioprotection by Remote Ischemic Preconditioning in Humans

Rationale: The heart can be protected from infarction by brief episodes of ischemia/reperfusion of a remote organ. Remote ischemic preconditioning (RIPC) by brief arm ischemia/reperfusion has been recruited in patients undergoing coronary artery bypass surgery or percutaneous coronary interventions and during transport to the hospital for acute myocardial infarction. Cardioprotective signaling has been extensively characterized in animal experiments. Objective: To identify cardioprotective signaling by RIPC in humans. Methods and Results: RIPC was induced by 3 cycles of 5 minutes of arm ischemia/5 minutes of reperfusion in patients undergoing coronary artery bypass surgery. Twelve patients each were randomly assigned to undergo RIPC or a sham control procedure. Protection was confirmed by reduced serum troponin I concentrations in patients with RIPC versus control patients. In myocardial biopsies, an array of established cardioprotective proteins was analyzed by Western immunoblotting. The phosphorylation of signal transducer and activator of transcription 5 (STAT5) increased from baseline before ischemic cardioplegic arrest to 10 minutes of reperfusion with RIPC, and STAT5 phosphorylation during reperfusion was greater in patients with RIPC than in control patients. Conclusions: The identification of this unique signaling signature of RIPC will facilitate the development of pharmacological cardioprotection. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01406678.

Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting

OBJECTIVE Remote ischemic preconditioning protects the myocardium from ischemia/reperfusion injury. We recently identified protection by remote ischemic preconditioning to be associated with the activation of signal transducer and activator of transcription 5 in left ventricular biopsy specimens of patients undergoing coronary artery bypass grafting during isoflurane anesthesia. Because remote ischemic preconditioning did not protect the heart during propofol anesthesia, we hypothesized that propofol anesthesia interferes with signal transducer and activator of transcription 5 activation. METHODS In a randomized, single-blind, placebo-controlled, prospective study, we analyzed an array of established cardioprotective proteins during propofol anesthesia with or without remote ischemic preconditioning in 24 nondiabetic patients with 3-vessel coronary artery disease. RESULTS Remote ischemic preconditioning (n = 12) compared with no remote ischemic preconditioning (n = 12) failed to decrease the area under the troponin I time curve (273 ± 184 ng/mL × 72 hours vs 365 ± 301 ng/mL × 72 hours; P = .374). Although phosphorylation of several protein kinases was increased from baseline to reperfusion, signal transducer and activator of transcription 5 phosphorylation was not increased and was not different between the remote ischemic preconditioning and no remote ischemic preconditioning groups. CONCLUSIONS Remote ischemic preconditioning during propofol anesthesia did not evoke either signal transducer and activator of transcription 5 activation or cardioprotection, implying interaction of propofol with cardioprotective signaling upstream of signal transducer and activator of transcription 5.

Vascular Access Site Complications after Percutaneous Transfemoral Aortic Valve Implantation

Background and Purpose:Transcatheter aortic valve implantation (TAVI) is a rapidly emerging treatment option for patients with aortic valve stenosis and high surgical risk. Different access routes have been proposed for TAVI including transapical, transsubclavian and transfemoral, with percutaneous transfemoral being the preferred because least invasive and nonsurgical. However, vascular access site complications due to the large-bore delivery catheters remain an important clinical issue, particularly with respect to the elderly patient collective typically considered for TAVI. In the study, the authors analyzed their 4-year TAVI experience with respect to vascular complications and their management in patients undergoing completely percutaneous transfemoral TAVI procedures.Patients and Methods:Since 2006, TAVI was performed in 101 consecutive patients at the West German Heart Center Essen. 33 patients underwent transapical TAVI, eight patients transfemoral TAVI with surgical access or closure, and 60 patients percutaneous transfemoral TAVI using two commercially available prosthetic valve devices.Results:Completely percutaneous TAVI was technically successful in all but one patient with malpositioning in the aortic arch during valve retrieval. There was no intraprocedural death and 30-day mortality was 12% (7/60). Vascular access site complications occurred in 19 patients (32%), necessitating surgical repair in six of them (10%). Complications included retroperitoneal hematoma (n = 2), iliac or femoral artery dissection (n = 10), (pseudo)aneurysm formation (n = 3), and closure device-induced vessel stenosis/ occlusion (n = 6). Of these, 13 cases could be managed either conservatively (n = 5) or by contralateral endovascular treatment (n = 8).Conclusion:Completely percutaneous TAVI has a high acute success rate with low intraprocedural and 30-day mortality. The patient collective appears to be prone to vascular complications which remain an important limitation of this novel technique. Although conservative or endovascular management is possible in the majority of cases, further technological developments are obliged to reduce the vascular complication rate.ZusammenfassungHintergrund und Fragestellung:Die katheterbasierte Aortenklappenimplantation ist eine neue, in der klinischen Routine bereits breit angewandte Therapieoption für Hochrisikopatienten mit kalzifizierter Aortenklappenstenose. Während in der Anfangsphase noch eine chirurgische Freilegung der arteriellen Zugangsgefäße und damit verbunden eine Vollnarkose nötig waren, ist die Durchführung heute in einer rein perkutanen Technik und somit sogar unter Analgosedierung möglich. Aufgrund der großen Kaliber der zur Einführung und zum Vorschieben der Prothese benötigten Schleusen und Katheter birgt diese Prozedur jedoch das Risiko einer Verletzung der arteriellen Zugangsgefäße, insbesondere da diese bei den betroffenen, älteren Patienten häufig atherosklerotische Veränderungen aufweisen. Die vorliegende Untersuchung gibt einen Überblick über die vaskulären Komplikationen und mögliche Managementstrategien an einem Kollektiv von 60 konsekutiven Patienten, bei denen in rein perkutaner Technik eine transfemorale Aortenklappenimplantation durchgeführt wurde.Patienten und Methodik:Seit 2006 wurde am Westdeutschen Herzzentrum Essen bei insgesamt 101 konsekutiven Patienten eine kathetergesteuerte Aortenklappenimplantation durchgeführt, bei 33 Patienten über den transapikalen, bei 68 Patienten über den transfemoralen Zugang. Während bei den initialen acht in transfemoraler Technik behandelten Patienten noch eine chirurgische Freilegung und/oder ein chirurgischer Verschluss der Zugangsgefäße durchgeführt wurde, erfolgte die Implantation der ballonexpandierbaren Edwards-Sapien- (n = 41) und der selbstexpandierbaren CoreValve-Prothese (n = 19) bei de hemofolgenden 60 Patienten in rein perkutaner Technik unter Verwendung von Nahtverschlusssystemen.Ergebnisse:Bis auf eine Fehlpositionierung im Aortenbogen konnten alle Aortenklappenprothesen erfolgreich in rein perkutaner Technik und ohne intraprozeduralen Todesfall implantiert werden. Die 30-Tage-Mortalität betrug 12%. Postinterventionell zeigte sich eine signifikante Verbesserung der Hämodynamik mit Abfall des mittleren transaortalen Druckgradienten von 52 ± 18 auf 13 ± 6 mmHg und einer Zunahme der Klappenöffnungsfläche von 0,6 ± 0,2 auf 1,5 ± 0,3 cm2. Die Rate an vaskulären Komplikationen betrug 32% (19 von 60 Patienten). Die Komplikationen beinhalteten zwei retroperitoneale Hämatome, zehn Dissektionen der Femoral- und Iliakal gefäße, drei Aneurysmabildungen und sechs ver schluss systeminduzierte Komplikationen. In fünf Fällen erfolgte eine konservative Therapie, bei acht Patienten konnte eine katheterinterventionelle Behandlung durchgeführt werden. Eine operative Sanierung war bei sechs Patienten (10%) nötig.Schlussfolgerung:Die transfemorale Aortenklappenimplantation kann heutzutage in rein perkutaner Technik mit einer hohen Erfolgsrate, geringer Mortalität und guten hämodynamischen und klinischen Ergebnissen durchgeführt werden. Vaskuläre Komplikationen sind jedoch noch häufig und stellen eine wichtige Limitation dieser neuen Technik dar. Obwohl ein konservatives oder interventionelles Management dieser Komplikationen in der Regel möglich ist, müssen zukünftige Weiterentwicklungen in besonderem Maße auch auf eine Reduktion der vaskulären Komplikationsrate gerichtet sein.

STAT5 activation and cardioprotection by remote ischemic preconditioning in humans: short communication.

Rationale: The heart can be protected from infarction by brief episodes of ischemia/reperfusion of a remote organ. Remote ischemic preconditioning (RIPC) by brief arm ischemia/reperfusion has been recruited in patients undergoing coronary artery bypass surgery or percutaneous coronary interventions and during transport to the hospital for acute myocardial infarction. Cardioprotective signaling has been extensively characterized in animal experiments. Objective: To identify cardioprotective signaling by RIPC in humans. Methods and Results: RIPC was induced by 3 cycles of 5 minutes of arm ischemia/5 minutes of reperfusion in patients undergoing coronary artery bypass surgery. Twelve patients each were randomly assigned to undergo RIPC or a sham control procedure. Protection was confirmed by reduced serum troponin I concentrations in patients with RIPC versus control patients. In myocardial biopsies, an array of established cardioprotective proteins was analyzed by Western immunoblotting. The phosphorylation of signal transducer and activator of transcription 5 (STAT5) increased from baseline before ischemic cardioplegic arrest to 10 minutes of reperfusion with RIPC, and STAT5 phosphorylation during reperfusion was greater in patients with RIPC than in control patients. Conclusions: The identification of this unique signaling signature of RIPC will facilitate the development of pharmacological cardioprotection. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01406678.

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 operating room concept for combined diagnostics, intervention and surgery in acute type A dissection †

OBJECTIVES In acute type A dissection (AAAD), it is commonly decided to carry out immediate surgical repair without invasive diagnostics. The hybrid operating room (Hybrid OR) concept encompasses simultaneous haemodynamic control, non-invasive and invasive diagnostics and immediate surgical and/or interventional treatment. Results over a seven-year period are presented here. METHODS From March 2004 to March 2011, 1883 cardiological and surgical patients were treated in a Hybrid OR. Of these, 124 patients (age 60 ± 13, 64% male) diagnosed with AAAD were operated upon. External computed tomography (CT) was available for 87% (108/124) of cases and angiography in 15% (19/124). Preoperative transoesophageal echocardiography (TEE) was done in all patients and angiography in 57% (71/124). Surgery was performed without angiography in 27% (34/124), of which 14% (17/124) was due to shock. Postoperative control angiography followed in 18% (22/124) due to suspected ongoing malperfusion. RESULTS Preoperative angiography was performed in 71 patients, and no angiography related complications were observed during the procedure. A total of 32% (23/71) of these underwent coronary artery bypass graft (CABG)--for newly-diagnosed coronary artery disease in 21% of cases and for coronary malperfusion in 11%. Visceral/peripheral malperfusion syndromes, necessitating primary endovascular intervention, were detected in 23% (16/71). Ascending aorta replacement was performed in 100% (124/124) of patients, arch replacement in 88% (109/124) and descending aorta repair in 35% (44/124). Five postoperative endovascular interventions became necessary due to persistent malperfusion. In-hospital mortality was 13% (12/90) in patients who had undergone preoperative invasive diagnostics and 24% (8/34) in patients who had not. CONCLUSIONS The Hybrid OR concept enables the exact diagnosis of coronary status and downstream malperfusion sites and influences the design of surgical and/or endovascular treatment, without time delay and at negligible risk to the patient.

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

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.