BackgroundRemote 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.MethodsIn 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.ResultsFive 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 = 0.041).ConclusionsRemote 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.

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 (3 cycles of 5 min left upper arm ischemia and 5 min 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 72 h. 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.

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.

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.

Background: Near-infrared spectroscopy (NIRS) for brain monitoring has an uncertain value. We prospectively assessed the association of decreased NIRS tissue oxygenation index (TOI) with cerebral events in adults undergoing aortic arch repair with hypothermic circulatory arrest and bilateral antegrade selective cerebral perfusion. Methods: 76 consecutive patients (mostly aortic arch dissections/aneurysms) were studied. Desaturation was defined as unilateral or bilateral TOI decrease to <50% or to <80% of the individual patients’ baseline. No intervention was based on TOI data and the end-point was postoperative cerebral events shown by imaging. Results: Baseline TOI on left/right foreheads averaged 70.4% ± 10.8 (SD) and 67.9% ± 9.1, and did not change significantly thereafter. Twentysix of 76 patients (34%) showed a TOI decrease to <50% and 55 (72%) a decrease to <80% from baseline. Cerebral complications occurred in 26/76 patients (34%), i.e., regional brain infarction (n=22) or edema (n=4). Twenty-six of 76 (34%) patients, 11 (42%) with and 15 (58%) without decreased TOI, had cerebral events but neither absolute TOI nor its decrease from baseline was predictive (p=0.206). Conversely, in patients with events, the incidence of decreased TOI was not different (11 vs. 15 of 26; 42% vs. 58%; p=0.206), whereas duration of hypothermic circulatory arrest (59min ± 34 vs. 43 ± 33, p=0.049) and bilateral antegrade selective cerebral perfusion (66min ± 27 vs. 50 ± 26, p=0.013), hospital-stay (p=0.001), and mortality (p=0.014) were

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, β-blockers, statins, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and intraoperative nitroglycerine did not impact on TnI release.CONCLUSION:Age, gender, β-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.

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.

Introduction: Acute type A aortic dissection (ATAAD) is rapidly lethal and requires comprehensive tactics and decision making. To refine our respective approach we retrospectively analyzed our patients undergoing urgent surgery in our hybrid operating room over a 10 year period for the impact of immediate preoperative coronary angiography (CA), aortography, and/or intravascular ultrasound (IVUS) for the detection of coronary artery disease (CAD) and/or arterial malperfusion. Methods: 136 patients (mean age: 60.6 y ± 13; 63% male, March 2004-February 2014) underwent preoperative CA with or without IVUS. We assessed the time interval from preoperative CA to surgery and the impact for concomitant coronary artery bypass grafting (CABG) or endovascular interventions. Results: The delay to proceed with surgery due to preoperative catheterization averaged 32 min ± 26 (Fig. 1) in the setting of the hybrid OR. CA revealed CAD in 47/136 (35%) patients, with CABG consequently performed in 38 (28%). In 12 (9%) patients, CABG was necessary due to ostium obstruction by the dissection. 30-day mortality more than doubled in patients with concomitant CAD (27.7% vs. 11.2%, respectively, p<0.01). However in patients with confirmed CAD, mortality was less 19% (6/31), in those undergoing CABG, compared to 44% (7/16) for isolated aortic repair (p=0.08). Conclusions: In a hybrid operating room setting, preoperative coronary and aortic angiography do not unduly delay surgery, facilitate diagnosis of coronary malperfusion, and allowing concomitant CABG in as much as 28% of patients.

Coronary flow velocity reserve (CVR) is reduced in patients with severe symptomatic aortic stenosis, contributing to ischemic clinical symptoms. We evaluated coronary flow dynamics assessed by intracoronary Doppler surveillance of the blood flow in the left anterior descending (LAD) artery during

Background: A postprocedural increase of the serum troponin I concentration (TnI) reflects myocardial injury and occurs frequently during transcatheter aortic valve implantation (TAVI). Periprocedural coronary microembolization is a potential cause of such injury. We therefore evaluated each step of the transfemoral TAVI procedure for coronary embolization using intracoronary Doppler (ICD) in the left anterior descending (LAD) artery. Methods: 15 high-risk patients with severe, symptomatic aortic valve stenosis (age 79 ± 45 yrs; EuroScore 17 ± 4%) who underwent transfemoral TAVI using the balloon-expandable Edwards bioprosthesis were included. ICD examinations were recorded and evaluated off-line for high-intensity transient signals (HITS). Perioperative concentrations of TnI were serially measured within the first 72 h after TAVI, and a cardiac MRI with late gadolinium-enhancement (LGE) was performed within 7 days. Results: HITS were detected in all patients (figure 1), mostly during the initial crossing of the native valve and positioning of the prosthesis with subsequent implantation. TnI peaked at 24 h after TAVI (3.17 ng/ml), and LGE was observed in only one single case. There was no correlation between amount of HITS and TnI area under the curve in the first 72 h after TAVI. Conclusions: Procedural HITS were detected by ICD in all patients undergoing transfemoral TAVI. The highest amount of HITS was observed during initial valve passage and positioning of the prosthesis with subsequent implantation. However, no association was found between the number of HITS and myocardial injury, as reflected by increased serum TnI concentrations or LGE on cardiac MRI.

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 (3x5 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 x 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.

We read with great interest the article by Kottenberg and colleagues1Kottenberg E. Musiolik J. Thielmann M. Jakob H. Peters J. Heusch G. Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting.J Thorac Cardiovasc Surg. March 1, 2013; ([Epub ahead of print])Google Scholar published online in The Journal of Thoracic and Cardiovascular Surgery on March 1, 2013. They have done a series of impressive translational works to explore the underlying mechanisms of cardioprotection by remote ischemic preconditioning (RIPC) with isoflurane or propofol in patients undergoing coronary artery bypass grafting (CABG).1Kottenberg E. Musiolik J. Thielmann M. Jakob H. Peters J. Heusch G. Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting.J Thorac Cardiovasc Surg. March 1, 2013; ([Epub ahead of print])Google Scholar, 2Kottenberg E. Thielmann M. Bergmann L. Heine T. Jakob H. Heusch G. et al.Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol: a clinical trial.Acta Anaesthesiol Scand. 2012; 56: 30-38Crossref PubMed Scopus (300) Google Scholar, 3Heusch G. Musiolik J. Kottenberg E. Peters J. Jakob H. Thielmann M. STAT5 activation and cardioprotection by remote ischemic preconditioning in humans: short communication.Circ Res. 2012; 110: 111-115Crossref PubMed Scopus (178) Google Scholar In their fundamental study published in Acta Anaesthesiologica Scandinavica,2Kottenberg E. Thielmann M. Bergmann L. Heine T. Jakob H. Heusch G. et al.Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol: a clinical trial.Acta Anaesthesiol Scand. 2012; 56: 30-38Crossref PubMed Scopus (300) Google Scholar they designed 2 independent substudies and found that isoflurane may be more effective in the preservation of cardioprotection by RIPC than propofol. Then, based on 2 consequently separated and independent studies,2Kottenberg E. Thielmann M. Bergmann L. Heine T. Jakob H. Heusch G. et al.Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol: a clinical trial.Acta Anaesthesiol Scand. 2012; 56: 30-38Crossref PubMed Scopus (300) Google Scholar, 3Heusch G. Musiolik J. Kottenberg E. Peters J. Jakob H. Thielmann M. STAT5 activation and cardioprotection by remote ischemic preconditioning in humans: short communication.Circ Res. 2012; 110: 111-115Crossref PubMed Scopus (178) Google Scholar they believed that differential activation of signal transducer and activator of transcription 5 (STAT 5) phosphorylation may be the contributing factor. Nevertheless, there remains inconclusive information about this interesting issue when looking into the fundamental study. In that study,2Kottenberg E. Thielmann M. Bergmann L. Heine T. Jakob H. Heusch G. et al.Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol: a clinical trial.Acta Anaesthesiol Scand. 2012; 56: 30-38Crossref PubMed Scopus (300) Google Scholar the male proportion may be even within the substudy (RIPC vs control with isoflurane; RIPC vs control with propofol); however, it may be uneven between the 2 substudies (isoflurane vs propofol, 89.7% vs 75.8%; mean difference, 14%). Accumulating evidence from animal studies has supported gender-specific cardioprotection by ischemic conditioning.4Penna C. Tullio F. Merlino A. Moro F. Raimondo S. Rastaldo R. et al.Postconditioning cardioprotection against infarct size and post-ischemic systolic dysfunction is influenced by gender.Basic Res Cardiol. 2009; 104: 390-402Crossref PubMed Scopus (67) Google Scholar Moreover, our recent study,5Zhou C. Yao Y. Zheng Z. Gong J. Wang W. Hu S. et al.Stenting technique, gender, and age are associated with cardioprotection by ischaemic postconditioning in primary coronary intervention: a systematic review of 10 randomized trials.Eur Heart J. 2012; 33: 3070-3077Crossref PubMed Scopus (73) Google Scholar including 10 randomized trials using the meta-regression method found an increased effect size (standardized mean difference) in postintervention myocardial enzyme levels of ischemic postconditioning by 0.22 per 10% increase in male proportion (Figure 1), indicating that a study with more male patients may result in a more pronounced effect than a study with fewer male patients. Hence, in their fundamental study, the authors cannot exclude the potential role of gender disparity in the quasi preservation of cardioprotection by RIPC with isoflurane, but not propofol, in CABG. At least, as the authors stated in the limitation section, both positive and negative controls are essential in one study, especially for the exploration of the role of STAT 5. The cardioprotective difference between isoflurane and propofol in the setting of RIPC needs further more rigorous studies. Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass graftingThe Journal of Thoracic and Cardiovascular SurgeryVol. 147Issue 1PreviewRemote 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. Full-Text PDF Reply to the EditorThe Journal of Thoracic and Cardiovascular SurgeryVol. 146Issue 3PreviewWe thank Zhou and colleagues for their comments and interest in our recent work.1,2 We appreciate that they considered us to have done a series of impressive translational studies to explore the mechanisms of cardioprotection by remote ischemic preconditioning (RIPC) with isoflurane or propofol in patients undergoing coronary artery bypass grafting (CABG) surgery.1-3 Full-Text PDF

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 x 72 hours vs 365 +/- 301 ng/mL x 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.

HomeCirculationVol. 127, No. 18Letter by Giannini et al Regarding Article, "Cerebral Embolization During Transcatheter Aortic Valve Implantation: A Transcranial Doppler Study" Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBLetter by Giannini et al Regarding Article, "Cerebral Embolization During Transcatheter Aortic Valve Implantation: A Transcranial Doppler Study" Nicola Giannini, MD Francesco De Caro, MD Alberto Chiti, MD Nicola GianniniNicola Giannini Department of NeuroscienceClinic of NeurologyUniversity of PisaPisa, Italy Francesco De CaroFrancesco De Caro Cardiac Catheterization LaboratoryCardiothoracic and Vascular DepartmentUniversity of PisaPisa, Italy Alberto ChitiAlberto Chiti Department of NeuroscienceClinic of NeurologyUniversity of PisaPisa, Italy Originally published7 May 2013https://doi.org/10.1161/CIRCULATIONAHA.112.149658Circulation. 2013;127:e589To the Editor:We read with great interest the article of Kahlert et al1 that confirms the role of transcatheter aortic valve implantation as a safe procedure, performable on patients at high operatory risk who cannot undergo traditional surgical aortic valve replacement, and evidences the role of transcranial Doppler procedural monitoring to detect microembolic signals generated by the fragmentation of atheromas of the aortic arch and of the native aortic valve.A small number of periprocedural neurological events was observed in the authors' casistic (1 fatal stroke and 1 minor stroke on 83 procedures) in front of a high microembolic load and diffusion-weighted magnetic resonance imaging signal abnormalities, both surrogate parameters of procedural tolerance.First, not all microemboli are dangerous; in fact, to give an ischemic injury, there also are possible hemodynamic factors such as a reduced mean flow velocity in middle cerebral arteries that would slow down the clearance of microemboli.2 By the way, transcranial Doppler monitoring of middle cerebral arteries also records the cerebral hemodynamic changes due to prolonged arrhythmias or rapid right ventricular pacing in the balloon dilation phase.On the other hand, signal hyperintensities in diffusion-weighted imaging sequences detected by early postprocedural magnetic resonance imaging are often reversible; in fact, a real ischemic lesion is not all that bright, but might be linked to reversible disturbances in cellular metabolism (they have also been associated with hypotension, seizure, migraine, or hypoglycemia),3 especially where signal abnormalities are detected in diffusion-weighted imaging sequences but not in fluid-attenuated inversion recovery or T2 sequences.4Nicola Giannini, MDDepartment of NeuroscienceClinic of NeurologyUniversity of PisaPisa, ItalyFrancesco De Caro, MDCardiac Catheterization LaboratoryCardiothoracic and Vascular DepartmentUniversity of PisaPisa, ItalyAlberto Chiti, MDDepartment of NeuroscienceClinic of NeurologyUniversity of PisaPisa, ItalyDisclosuresNone.References1. Kahlert P, Al-Rashid F, Döttger P, Mori K, Plicht B, Wendt D, Bergmann L, Kottenberg E, Schlamann M, Mummel P, Holle D, Thielmann M, Jakob HG, Konorza T, Heusch G, Erbel R, Eggebrecht H. Cerebral embolization during transcatheter aortic valve implantation: a transcranial Doppler study.Circulation. 2012; 126:1245–1255.LinkGoogle Scholar2. Orlandi G, Fanucchi S, Gallerini S, Sonnoli C, Cosottini M, Puglioli M, Sartucci F, Murri L. Impaired clearance of microemboli and cerebrovascular symptoms during carotid stenting procedures.Arch Neurol. 2005; 62:1208–1211.CrossrefMedlineGoogle Scholar3. Kahlert P, Knipp SC, Schlamann M, Thielmann M, Al-Rashid F, Weber M, Johansson U, Wendt D, Jakob HG, Forsting M, Sack S, Erbel R, Eggebrecht H. Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study.Circulation. 2010; 121:870–878.LinkGoogle Scholar4. Cosottini M, Michelassi MC, Puglioli M, Lazzarotti G, Orlandi G, Marconi F, Parenti G, Bartolozzi C. Silent cerebral ischemia detected with diffusion-weighted imaging in patients treated with protected and unprotected carotid artery stenting.Stroke. 2005; 36:2389–2393.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails May 7, 2013Vol 127, Issue 18 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.112.149658PMID: 23648684 Originally publishedMay 7, 2013 PDF download Advertisement

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.

Since cardiac surgery began, surgeons have aimed to find methods of minimizing myocardial injury resulting from ischemia and reperfusion. The concept of somehow conditioning the heart in order to attenuate ischemia and reperfusion-related injury has evolved in cardiovascular research over decades, from ischemic preconditioning and postconditioning to, more recently, remote ischemic preconditioning (and postconditioning). Although many strategies have proven to be beneficial in the experimental arena, a few have been successfully translated into clinical practice. Remote ischemic preconditioning, with the use of brief episodes of ischemia and reperfusion of vascular territories remote from the heart, has been shown convincingly to decrease myocardial injury. To date, the translation of this powerful innate mechanism of myocardial and/or multiorgan protection from the animal lab to the operating theatre, using transient occlusion of blood flow to the upper limb with a blood-pressure cuff before cardiac surgery, has shown promising results, with several proof-of-principle and first randomized controlled clinical trials reporting benefits for patients undergoing cardiac surgery. If the efficacy of remote ischemic preconditioning can be conclusively proven, the clinical applications in cardiac surgery could be almost infinite, providing multiorgan protection in various surgical scenarios.

Objectives: ‘Total-arterial9 and ‘complete9 revascularization are cardiac surgical principles that have been proven to beneficially impact outcomes in coronary artery bypass graft (CABG) surgery. The use of bilateral internal thoracic artery (BITA) with T-grafting is an approach that can achieve both. Methods: Between January 2004 and March 2012, a total of 408 patients underwent first-time, isolated CABG surgery using BITA with T-grafting. Patients were analyzed for mortality and major adverse cardiac and cerebrovascular events (MACCE). Prospectively recorded clinical data were screened for all-cause death, MACCE, and repeat angina & revascularization at 30 days and at follow-up. Logistic regression models were constructed to identify predictors for short- and long-term survival. Results: Patients (age, 63±10 years [mean±SD], 21% female) presented triple-vessel coronary artery disease in 95% and risk factors for BITA use, such as obesity, diabetes, or COPD were present in 36%, 23% and 11% of the patients. BITA was used for T-grafting in all patients. Mean bypass time and ischemic time was 105±28 min and 77±19 min with 4.0±0.9 distal coronary anastomoses constructed per patient. Mean transit time graft flow measured at the T-graft was 115±51mL/min. Thoracic re-exploration rate was 2.5% and sternal wound dehiscence9s occurred in 3.7% of the patients within the entire follow-up period. All-cause mortality was 1.0% (cardiac-related death 0.7%) and MACCE rate 4.7% at 30 days. Kaplan-Meier survival estimates were 97.4% at 1 year, 96.5% at 5 years, and 95.2 at 8 years of follow-up with a mean follow-up time of 4.7±2.2 years and a completeness of follow-up of 95.6%. Multivariate logistic regression analyses identified body weight ( P =0.02) as an independent risk factor for death and COPD ( P =0.02) as an independent risk factor for MACCE, whereas LV-function ( P P =0.04), and COPD ( P =0.02) were identified as risk factors for long-term survival. Conclusion: Complete and total-arterial revascularization in multi-vessel coronary artery disease can be achieved by the use of BITA and T-grafting with satisfying short-term and excellent long-term outcomes.

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.

Background: Remote ischemic preconditioning (RIPC) reduced myocardial injury following coronary artery bypass graft (CABG) surgery in recent proof-of-concept and small randomized controlled trials ...