Remote ischaemic preconditioning increases serum extracellular vesicle concentrations with altered micro-RNA signature in CABG patients.

BACKGROUND: Remote ischaemic preconditioning (RIPC) can attenuate myocardial ischaemia/reperfusion injury but its underlying mechanisms remain largely unknown. Recently, extracellular vesicles (EVs) containing microRNAs (miRNAs) were shown to mediate distant intercellular communication that may be involved in cardioprotection. We tested the hypothesis that RIPC in anaesthetized patients undergoing coronary artery bypass (CABG) surgery results in the release of EVs from the ischaemic/reperfused arm into the blood stream harbouring cardioprotective miRNAs. METHODS: In 58 patients randomised to RIPC (three 5/5 minutes episodes of left arm ischaemia/reperfusion by suprasystolic blood pressure cuff inflations/deflations) or Sham, a subprotocol comprising of parallel right radial artery and regional (left subclavian) venous blood sampling before (awake) and 5 and 60 minutes after RIPC/Sham during isoflurane/sufentanil anaesthesia could be completed. EVs were extracted by polymer-based precipitation methods, their concentrations measured, and their miRNA signature analysed. RESULTS: Five minutes after RIPC, regional venous EV concentrations downstream from the cuff increased and arterial concentrations increased after 60 minutes (fold change [fc]: RIPC: 1.33 ± 0.5, Sham: 0.91 ± 0.31; P = 0.003 for interaction). Already 5 minutes after RIPC, expression of 26 miRNAs (threshold fc: 3.0, P < 0.05) isolated from EVs including the cardioprotective miR-21 had increased. RIPC also decreased postoperative Troponin I concentrations (AUC RIPC: 336 ng/mL × 72 hours ± 306 vs Sham: 713 ± 1013; P  = â€Š0.041). CONCLUSIONS: Remote ischaemic preconditioning increases serum EV concentrations, most likely by early EV release from the patients' left (RIPC) arm, alters their miRNA signature, and is associated with myocardial protection. Thus, an increased EV concentration with an altered miR-signature may mediate the RIPC effect.

Confounders of Cardioprotection by Remote Ischemic Preconditioning in Patients Undergoing Coronary Artery Bypass Grafting.

OBJECTIVES: Remote ischemic conditioning (RIC) by repetitive blood pressure cuff inflation/deflation around a limb provides cardioprotection in patients undergoing coronary artery bypass grafting (CABG). Cardioprotection is confounded by risk factors, comorbidities and comedications. We aimed to identify confounders that possibly attenuate the protection provided by RIC. METHODS: In a retrospective analysis of our single-center, randomized, double-blind trial of patients undergoing elective CABG with/without RIC prior to ischemic cardioplegic arrest, we analyzed demographics, medications and intraoperative variables. The primary end point was myocardial injury, as reflected by the area under the curve for serum troponin I (TnI) from baseline to 72 h after surgery. RESULTS: In models with 2 independent variables and in the multivariate analysis, age and aortic cross-clamp time impacted on TnI release. Subgroup analyses confirmed RIC-induced protection in all age tertiles. There was no protection with an aortic cross-clamp time ≤56 min (RIC/control = 1.026 not significant), but there was protection with 57-75 min (RIC/control = 0.757; p = 0.0348) and ≥76 min (RIC/control = 0.735; p = 0.0277). Gender, ß-blockers, statins, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and intraoperative nitroglycerine did not impact on TnI release. CONCLUSION: Age, gender, ß-blockers, statins, ACE inhibitors, ARBs and intraoperative nitroglycerine have no significant impact on RIC-induced cardioprotection during CABG. However, greater myocardial ischemia/reperfusion injury at longer cross-clamp time facilitates the detection of protection by RIC.

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.

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.

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 [MCV(TF)], n=32; Edwards Sapien [ES(TF)], n=26) and transapical (ES(TA): 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 (ES(TF), 259.9 [184.8-334.9]; ES(TA), 206.1[162.5-249.7]; MCV(TF), 78.5 [25.3-131.6]; P<0.001) and the self-expandable MCV prosthesis during implantation (MCV(TF), 397.1 [302.1-492.2]; ES(TF), 88.2 [70.2-106.3]; ES(TA), 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.

Incidence, predictors, origin and prevention of early and late neurological events after transcatheter aortic valve implantation (TAVI): a comprehensive review of current data.

Transcatheter aortic valve implantation (TAVI) is a novel treatment option for patients with severe, symptomatic aortic valve stenosis considered inoperable or at high risk for surgical aortic valve replacement. Despite rapid adoption of this technology into clinical application, however, recent randomized controlled clinical trials have raised safety concerns regarding an increased risk of neurological events with TAVI compared to both medical treatment and conventional, surgical aortic valve replacement. Moreover, neuro-imaging studies have revealed an even higher incidence of new, albeit clinically silent cerebral lesions as a surrogate for procedural embolization. In this article, we review currently available data on the incidence, timing, predictors, prognostic implications and potential mechanisms of neurological events after TAVI.

First-line therapy with coagulation factor concentrates combined with point-of-care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery: a retrospective, single-center cohort study.

INTRODUCTION: Blood transfusion is associated with increased morbidity and mortality. We developed and implemented an algorithm for coagulation management in cardiovascular surgery based on first-line administration of coagulation factor concentrates combined with point-of-care thromboelastometry/impedance aggregometry. METHODS: In a retrospective cohort study including 3,865 patients, we analyzed the incidence of intraoperative allogeneic blood transfusions (primary endpoints) before and after algorithm implementation. RESULTS: Following algorithm implementation, the incidence of any allogeneic blood transfusion (52.5 vs. 42.2%; P < 0.0001), packed red blood cells (49.7 vs. 40.4%; P < 0.0001), and fresh frozen plasma (19.4 vs. 1.1%; P < 0.0001) decreased, whereas platelet transfusion increased (10.1 vs. 13.0%; P = 0.0041). Yearly transfusion of packed red blood cells (3,276 vs. 2,959 units; P < 0.0001) and fresh frozen plasma (1986 vs. 102 units; P < 0.0001) decreased, as did the median number of packed red blood cells and fresh frozen plasma per patient. The incidence of fibrinogen concentrate (3.73 vs. 10.01%; P < 0.0001) and prothrombin complex concentrate administration (4.42 vs. 8.9%; P < 0.0001) increased, as did their amount administered per year (179 vs. 702 g; P = 0.0008 and 162 × 10³ U vs. 388 × 10³ U; P = 0.0184, respectively). Despite a switch from aprotinin to tranexamic acid, an increase in use of dual antiplatelet therapy (2.7 vs. 13.7%; P < 0.0001), patients' age, proportion of females, emergency cases, and more complex surgery, the incidence of massive transfusion [(≥10 units packed red blood cells), (2.5 vs. 1.26%; P = 0.0057)] and unplanned reexploration (4.19 vs. 2.24%; P = 0.0007) decreased. Composite thrombotic/thromboembolic events (3.19 vs. 1.77%; P = 0.0115) decreased, but in-hospital mortality did not change (5.24 vs. 5.22%; P = 0.98). CONCLUSIONS: First-line administration of coagulation factor concentrates combined with point-of-care testing was associated with decreased incidence of blood transfusion and thrombotic/thromboembolic events.

Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest.

Remote ischemic preconditioning (RIPC) with transient upper limb ischemia reduces myocardial injury in patients undergoing on-pump coronary artery bypass grafting (CABG) with cross-clamp fibrillation or blood cardioplegia for myocardial protection. Whether or not such protection is still operative when standard crystalloid cardioplegic arrest is used is uncertain. Fifty-three consecutive, non-diabetic patients with triple-vessel disease and 64 +/- 12 years of age (mean +/- SD), who underwent elective CABG surgery with crystalloid (Bretschneider) cardioplegic arrest, were allocated in a prospective, randomized, single-blinded protocol to receive either a RIPC protocol (3 cycles of 5 min transient left upper arm ischemia induced by inflating a blood pressure cuff to 200 mmHg with 5 min of reperfusion) or control, respectively, after induction of anesthesia. Cardiac troponin I (cTnI) concentration was measured preoperatively and over 72 h postoperatively, and the area under the curve (AUC) was calculated. Peak postoperative cTnI concentration was significantly reduced from 13.7 +/- 7.7 ng/mL in controls to 8.9 +/- 4.4 ng/mL in RIPC (P = 0.008). Mean cTnI concentration was significantly lower at 6, 12, 24, and 48 h after surgery (ANOVA; P < 0.0001) in the RIPC patients (N = 27) than in controls (N = 26), resulting in a 44.5% reduction of cTnI (AUC at 72 h). RIPC by repetitive inflation of a cuff around the left upper arm before surgery enhances myocardial protection in patients undergoing CABG surgery with antegrade cold crystalloid cardioplegia.

[Minimally invasive heart and mitral valve surgery]. / Minimalinvasive Herz- und Mitralklappenchirurgie.

During the last decades, minimally invasive operative techniques have been established in various subspecialties of modern cardiac surgery, offering now safe and efficient alternative treatment options for most of the patients. Those new and innovative options thereby aimed to reduce the operative trauma and perioperative morbidity, and furthermore, to increase patients' satisfaction and optimize patients' security. After continuous enhancement of these minimally invasive techniques during the last 10 years, numerous current reports demonstrate minimally invasive cardiac surgery techniques to be safe and efficient, resulting in equal or even better mortality and morbidity compared to conventional cardiac surgery. The underlying benefits of minimally invasive cardiac surgery are characterized by shorter hospital stay, less postoperative pain, accelerated rehabilitation, and superior cosmetic results. Minimally invasive treatment options in cardiac surgery should always be considered for suitable patients.

[Anesthesia with transfemoral and transapical aortic valve implantation. Periinterventional management and hemodynamic observations]. / Anästhesie bei transfemoraler und transapikaler Aortenklappenimplantation: Periinterventionelles Vorgehen und hämodynamische Beobachtungen.

Percutaneous transfemoral and transapical aortic valve implantations are novel procedures that often confront the anesthesiologist with bigger challenges than surgical aortic valve replacements using cardiopulmonary bypass. Due to old age and the presence of severe comorbidities including pulmonary vascular hypertension, most patients have a very high risk. Individual comorbidities and their severity are as important for the choice of the anesthetic technique as pharmacological cardiovascular therapy and communication during the respective phases of the intervention. Since severe hemodynamic alterations (cardiogenic shock, coronary ischemia, arrhythmias) and potential interventional complications (bleeding, ventricular and vascular injury) may occur, the authors routinely perform an extended cardiovascular monitoring. General endotracheal anesthesia may be advantageous even for transfemoral valve implantation and was not associated with a worse outcome. Following valve implantation a substantial increase in cardiac index, but also of all filling pressures was measured. Anesthesia coverage time for the first 100 cases averaged 263 min (+/- 96) for transfemoral and 297 (+/- 78) for transapical valve implantation, which appears greater than for conventional aortic valve replacement surgery, but it decreased significantly for transfemoral valve implantation over the course of interventions. Accordingly, the anesthesiologist, besides providing anesthesia and managing the airway, assumes responsibility for invasive cardiopulmonary monitoring, cardiovascular pharmacotherapy tailored to intervention phases, and "troubleshooting" in the event of complications for these still developing interventions.

[Experience and learning curve with transapical aortic valve implantation]. / Erfahrungen und Lernkurve mit der transapikalen Aortenklappenimplantation.

BACKGROUND AND PURPOSE: Transapical transcatheter aortic valve implantation has emerged as an alternative to conventional aortic valve replacement in high-risk patients with degenerative aortic valve stenosis. The aim of this study was to assess a potential learning curve with the former technique based on the own experience with this novel procedure. PATIENTS AND METHODS: 40 consecutive high-risk patients (82 +/- 5 years, logistic EuroSCORE 42% +/- 16%) with symptomatic aortic valve stenosis underwent transapical aortic valve implantation (balloon expandable Sapien bioprosthesis, Edwards Lifesciences, Irvine, CA, USA) in the hybrid operating room between October 2007 and May 2009 at the West German Heart Center Essen. To assess a potential learning curve, patients were allocated and compared according to the implantation date (initial n = 20: 10/2007 to 10/2008; second n = 20: 11/2008 to 05/2009). RESULTS: All but one transapical aortic valve implantations were successful (procedural success rate 97.5%) and no prosthesis migration/embolization or coronary artery obstruction was observed. Comparing the groups, procedural time, fluoroscopy time, and contrast media volume decreased significantly (139 +/- 30 min vs. 112 +/- 41 min; 6.8 +/- 1.9 min vs. 5.5 +/- 1.5 min; 226 +/- 75 ml vs. 169 +/- 23 ml; p

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.

Potential humoral mediators of remote ischemic preconditioning in patients undergoing surgical coronary revascularization.

Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion may reduce myocardial ischemia/reperfusion injury and improve patients' prognosis after elective coronary artery bypass graft (CABG) surgery. The signal transducer and activator of transcription (STAT)5 activation in left ventricular myocardium is associated with RIPC´s cardioprotection. Cytokines and growth hormones typically activate STATs and could therefore act as humoral transfer factors of RIPC´s cardioprotection. We here determined arterial plasma concentrations of 25 different cytokines, growth hormones, and other factors which have previously been associated with cardioprotection, before (baseline)/after RIPC or placebo (n = 23/23), respectively, and before/after ischemic cardioplegic arrest in CABG patients. RIPC-induced protection was reflected by a 35% reduction of serum troponin I release. With the exception of interleukin-1α, none of the humoral factors changed in their concentrations after RIPC or placebo, respectively. Interleukin-1α, when normalized to baseline, increased after RIPC (280 ± 56%) but not with placebo (97 ± 15%). The interleukin-1α concentration remained increased until after ischemic cardioplegic arrest and was also higher than with placebo in absolute concentrations (25 ± 6 versus 16 ± 3 pg/mL). Only interleukin-1α possibly fulfills the criteria which would be expected from a substance to be released in response to RIPC and to protect the myocardium during ischemic cardioplegic arrest.

Proteomics/phosphoproteomics of left ventricular biopsies from patients with surgical coronary revascularization and pigs with coronary occlusion/reperfusion: remote ischemic preconditioning.

Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion reduces myocardial ischemia/reperfusion injury. In left ventricular (LV) biopsies from patients undergoing coronary artery bypass grafting (CABG), only the activation of signal transducer and activator of transcription 5 was associated with RIPC's cardioprotection. We have now used an unbiased, non-hypothesis-driven proteomics and phosphoproteomics approach to analyze LV biopsies from patients undergoing CABG and from pigs undergoing coronary occlusion/reperfusion without (sham) and with RIPC. False discovery rate-based statistics identified a higher prostaglandin reductase 2 expression at early reperfusion with RIPC than with sham in patients. In pigs, the phosphorylation of 116 proteins was different between baseline and early reperfusion with RIPC and/or with sham. The identified proteins were not identical for patients and pigs, but in-silico pathway analysis of proteins with ≥2-fold higher expression/phosphorylation at early reperfusion with RIPC in comparison to sham revealed a relation to mitochondria and cytoskeleton in both species. Apart from limitations of the proteomics analysis per se, the small cohorts, the sampling/sample processing and the number of uncharacterized/unverifiable porcine proteins may have contributed to this largely unsatisfactory result.

No protection of heart, kidneys and brain by remote ischemic preconditioning before transfemoral transcatheter aortic valve implantation: Interim-analysis of a randomized single-blinded, placebo-controlled, single-center trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) reduces myocardial injury and improves clinical outcome in patients undergoing coronary revascularization, but only in the absence of propofol-anesthesia. We investigated whether RIPC provides protection of heart, kidneys and brain and improves outcome in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI). METHODS: Patients undergoing TF-TAVI were randomized to receive RIPC (3cycles of 5min left upper arm ischemia and 5min reperfusion) or placebo. The primary endpoint was myocardial injury, reflected by the area under the curve for serum troponin I concentrations (AUC-TnI) over the first 72h. Secondary endpoints included the incidences of periprocedural myocardial infarction, delayed gadolinium enhancement on postprocedural cardiac MRI, acute kidney injury, periprocedural stroke, and the incidence and volume of new lesions on postprocedural cerebral MRI. All-cause and cardiovascular mortality and major adverse cardiac and cerebrovascular events (MACCE) were assessed over 1-year follow-up. A prespecified interim-analysis was performed after the last patient had completed 1-year follow-up (NCT02080299). RESULTS: 100 consecutive patients were enrolled between September 2013 and June 2015. There were no significant between-group differences in the primary endpoint of peri-interventional myocardial injury (ratio RIPC/placebo AUC-TnI: 0.87, 95% CI: 0.57-1.34, p=0.53) or the secondary endpoints of cardiac, renal and cerebral impairment. There was no significant treatment effect in subgroup-analyses of patients undergoing cardiac or cerebral MRI. Mortality and MACCE did not differ. No RIPC-related adverse events were observed. CONCLUSIONS: RIPC did neither protect heart, kidneys and brain nor improve clinical outcome in patients undergoing TF-TAVI.

Myocardial injury during transfemoral transcatheter aortic valve implantation: an intracoronary Doppler and cardiac magnetic resonance imaging study.

AIMS: Myocardial injury reflected by a post-procedural increase of serum troponin I (TnI) occurs frequently during transcatheter aortic valve implantation (TAVI). It is potentially caused by intraprocedural hypotension, periprocedural coronary microembolisation and post-procedural (para)valvular leakages (PVLs). We invasively assessed coronary flow dynamics including coronary flow velocity reserve (CFVR), embolic high-intensity transient signals (HITS) as well as rapid pacing induced hypotension and post-procedural PVLs to determine their contribution to post-procedural TnI increases. METHODS AND RESULTS: In 15 transfemoral TAVI patients, TnI was measured serially, and cardiac MRIs with late gadolinium enhancement (LGE) were performed pre- and post-interventionally. There were no significant correlations between coronary flow dynamics, CFVR and the area under the curve (AUC) of TnI over 72 hours. Despite the detection of HITS in all patients and during all procedural steps, there was also no correlation between the amount of HITS and the AUC of TnI. However, there were positive correlations between the duration of rapid pacing as well as the time of subsequent blood pressure recovery and the AUC of TnI. Both LGE and more than mild PVL were observed in a single case only. CONCLUSIONS: Myocardial injury after TAVI appears to be related more to hypoperfusion-induced ischaemia than to periprocedural microembolisation.

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.

No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Remote ischemic preconditioning (RIPC) by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG). Activation of signal transducer and activator of transcription 5 (STAT5) in left ventricular (LV) myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy. METHODS: CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation) or placebo (cuff deflated) before skin incision (n = 10/10). Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline) and at early (5-10 min) reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002). Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5-12 (ATG5-12) complex, light chain 3 (LC3), parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2)-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion. RESULTS: Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02). STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05). CONCLUSION: Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion.