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.

A new self-expandable transcatheter aortic valve for transapical implantation: feasibility in acute and chronic animal experiments.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is currently expanding worldwide, however all available prostheses share some fundamental design drawbacks. We investigated the feasibility, safety and hemodynamic performance of the innovative transapical Acurate TA™ self-expandable device, which has the unique advantage of offering anatomically correct self-alignment within the aortic root. DESIGN: Transapical TAVI was performed in six acute swine and six chronic sheep procedures, with follow-up of 7, 14, 21, 28, 60 and 90 days. TAVI was performed under TEE and angiographic guidance without rapid pacing. RESULTS: A partial sternotomy approach was used to access the LV-apex. All valve implantations were performed as planned and all animals survived the implantation procedure. After deployment, no migration, embolization or coronary obstruction was observed during the observation period. Intraoperative TEE examination identified no signs of intravalvular leakage or valve dysfunction. Transvalvular mean pressure gradients were 5.4 ± 2.2 mmHg decreasing during follow-up (1.6 ± 0.8 mmHg, 1.8 ± 0.8 mmHg, 1.3 ± 0.2, 1.8 ± 0.7 mmHg, 1.6 ± 0.8 mmHg), with a slight increase atday 90 (4.0 ± 2.4 mmHg, P < 0.05). Macroscopic examination at necropsy showed correct anatomical positioning of the valve stent without any signs of structural valve deterioration. CONCLUSIONS: These first results of the innovative self-expandable transapical ACURATE TA™ device explore the feasibility and safety of anatomically correct off-pump implantation with optimal hemodynamic results.

Open balloon aortic valvuloplasty in aortic stenosis: implications for transcatheter aortic valve implantations.

Balloon aortic valvuloplasty (BAV) plays a crucial role in transcatheter aortic valve implantation (TAVI). However, data on morphology during BAV are lacking. During surgical aortic valve replacement, open BAV was performed as a non-therapeutic in-vivo model prior to aortic valve excision. Twenty-six patients with severe aortic stenosis were included in the study after ethics committee approval. A valvuloplasty balloon was advanced from the open aorta, across the stenotic aortic valve and was rapidly inflated and deflated. All patients except for one had tricuspid aortic valves with severe visible calcification on the aortic side of leaflets. All valves were successfully dilated. Only in the presence of severe central calcific noduli, fractures occurred in the middle portion of the leaflets in three and in the commissural part in four patients. No embolization of valvular debris occurred, however, ten coronary leaflets partially reached coronary orifices, resulting in three near-obstructions. The present study visualized for the first time the behaviour of bulky leaflet calcifications during valvuloplasty. Fractures in the middle portion of the free edge may occur whenever a huge calcification completely affects the whole leaflet area. No signs of embolization were observed, possibly explaining low stroke rates during TAVI procedures.

Heart-Type Fatty Acid Binding Protein and Ischemia-Modified Albumin for Detection of Myocardial Infarction After Coronary Artery Bypass Graft Surgery.

BACKGROUND: Heart-type fatty acid binding protein (hFABP) and ischemia-modified albumin (IMA) have been put forward as novel biomarkers to detect myocardial injury shortly after onset of ischemia. We compared hFABP and IMA with cardiac troponin I (cTnI) for speed and reliability in the diagnosis of perioperative myocardial infarction (PMI) after coronary artery bypass graft surgery (CABG). METHODS: In all, 210 consecutive patients undergoing isolated CABG with cardiopulmonary bypass were enrolled in a prospective study. Blood samples were taken perioperatively and throughout the first 72 hours after surgery; clinical data and events were recorded. In cohort A, serum concentrations of hFABP and cTnI were measured using a combined quantitative bedside assay. In cohort B, IMA and cTnI serum concentrations were measured using an albumin cobalt binding test. Perioperative myocardial infarction was defined using a cTnI cutoff of greater than 10.5 ng/mL occurring within 24 hours of CABG or new electrocardiographic changes. RESULTS: In cohort A, 14 patients were identified with PMI (group 1), whereas 94 had no PMI and served as controls (group 2). Both hFABP and cTnI were increased in group 1 as compared with group 2 (p < 0.001). Although cTnI did not differ before 12 hours, hFABP diverged much earlier, at 1 hour postoperatively (p < 0.001). An hFABP concentration of 20 µg/mL at 1 hour detected PMI with an area under the curve of 77.1%. In cohort B, 18 patients were identified with PMI (group 3), and 84 patients served as controls (group 4). No difference in cTnI values could be observed between the groups until 12 hours postoperatively. Ischemia-modified albumin failed to differentiate at any postoperative time point; the low discriminative power of IMA was confirmed with an area under the curve of 53.3% at 1 hour, 48.5% at 6 hours, and 39.3% at 12 hours postoperatively. CONCLUSIONS: Heart-type fatty acid binding protein is a sensitive and rapid biomarker that detected PMI reliably at 1 hour after CABG, much earlier than cTnI. The diagnostic value of IMA for detection of PMI appears to be very limited in this setting.

Low Incidence of Paravalvular Leakage With the Balloon-Expandable Sapien 3 Transcatheter Heart Valve.

BACKGROUND: We evaluated the clinical and hemodynamic performance of the new balloon-expandable Sapien 3 (Edwards Lifesciences, Irvine, CA) transcatheter heart valve (S3 THV). METHODS: Between April 2013 and January 2015, 54 consecutive high-risk patients presenting with aortic stenosis were treated with the new S3 THV. Clinical and hemodynamic data as well as device and procedure variables were obtained at baseline, intraoperatively and at 30-days according to Valve Academic Research Consortium-2. RESULTS: The S3 THV was implanted in 41 patients (44% female) via transapical access and in 13 patients via transaortic access. Patients were a mean ± standard deviation age of 80.3 ± 6.0 years. The mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of all patients was 33.3% ± 13.4%, the mean The Society of Thoracic Surgeons Score was 6.7% ± 5.3%, and the mean EuroSCORE II was 7.0% ± 5.5%. All patients underwent successful implantation (23 mm, n = 12; 26 mm, n = 22; 29 mm, n = 20), without any intraprocedural complications or repeat ballooning. At 30 days, 53 patients (97.8%) showed no or mild paravalvular aortic regurgitation, 1 patient (2.2%) showed moderate regurgitation, and no patients had more than moderate postprocedural aortic regurgitation. Stroke incidence was 3.7% (2 of 54), and all-cause mortality was 3.7% (2 of 54, sepsis and multiorgan failure). Two patients required a new pacemaker. At 30 days, all patients were in New York Heart Association Functional Class I or II, and the mean pressure gradients were 10.8 ± 3.6 mm Hg. CONCLUSIONS: The present study shows excellent clinical and hemodynamic outcomes of high-risk transapical valve replacement patients treated with the new S3 THV. The S3 THV shows a low incidence of postoperative aortic regurgitation, with 98% presenting with less than mild aortic regurgitation.

Transapical transcatheter aortic valve for severe aortic regurgitation: expanding the limits.

OBJECTIVES: This study sought to evaluate the self-expandable ACURATE TA device (Symetis SA, Ecublens, Switzerland) in a cohort of patients with pure aortic regurgitation (AR). BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been initially considered as an alternative for high-risk patients with aortic stenosis. Although the current experience is limited, TAVR might be also an alternative to treat patients with pure, severe AR. METHODS: Between April 2012 and December 2013, a total of 8 high-risk patients with pure, severe AR were enrolled (grade III+). Clinical and hemodynamic data as well as data on device and procedure parameters and outcomes were collected. RESULTS: Patient mean was 72.5 ± 8.4 years, and 37.5% of patients were female. Logistic EuroSCORE was 34.0 ± 7.9% and the Society of Thoracic Surgeons score was 7.3 ± 3.3% on average. Two patients had undergone emergency aortic operation before due to acute type A aortic dissection, and both were treated by replacement of the ascending aorta (including root reconstruction) and the aortic arch combined with or without E-vita Open stent graft (Jotec GmbH, Hechingen, Germany) (January 2011 and March 2012), whereas the other patients experienced primary AR. All patients underwent successful transapical TAVR with the transapical ACURATE TA device (size small, n = 1, size medium, n = 3, size large, n = 4) without any intraprocedural complications according to the Valve Academic Research Consortium 2 criteria. Post-procedure AR grade I+ or lower, as revealed by transoesophageal echocardiography and angiography, was present in all 8 patients. At 30 days, the stroke incidence and all-cause mortality rate were 0%. CONCLUSIONS: This small single-center series demonstrates the feasibility of transapical TAVR with the self-expandable ACURATE TA device in high-risk patients with severe AR.

Remote ischemic preconditioning: the surgeon's perspective.

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.

Prognostic significance of cardiac troponin I on admission for surgical treatment of acute pulmonary embolism: a single-centre experience over more than 10 years.

OBJECTIVES: Cardiac troponin I (cTnI) is a highly sensitive, specific marker for myocardial cell injury. We sought to determine whether cTnI on admission may help to identify patients with increased risk of open surgical embolectomy with acute pulmonary embolism (PE). METHODS: Forty-six consecutive patients with confirmed acute PE were enrolled in this prospective study. PE was confirmed by pulmonary angiography, computed tomography (CT) scan or echocardiography. Severity of PE was assessed by clinical data, and cTnI was measured within 12 h after admission. RESULTS: cTnI was elevated in 28 patients with acute PE. Preoperative right ventricular dysfunction [odds ratio (OR): 15.2; 95% confidence interval (CI): 2.02-144.8; P < 0.002], prolonged hypotension with cardiogenic shock (OR: 14.9; 95% CI: 2.2-131.1; P < 0.002) and preoperative need for resuscitation (OR: 6.0; 95% CI: 0.6-143.8; P = 0.12) were more prevalent in patients with elevated cTnI serum concentrations. cTnI-positive patients were also more likely to require inotropic support (OR: 10.0; 95% CI: 1.8-65.1; P < 0.005) and mechanical ventilation (OR: 13.5; 95% CI: 2.2-95.6; P < 0.005). Moreover, an elevated cTnI level on admission significantly correlated with both primary endpoints, in-hospital mortality (OR: 9.0; 95% CI: 1.0-215.2; P = 0.03) and major adverse clinical events (OR: 8.3; 95% CI: 1.5-62.5; P = 0.006). After multivariable risk adjustment, a positive cTnI value remained an independent predictor of in-hospital mortality (OR: 13.6; 95% CI: 3.22-145.8; P = 0.014) and major adverse clinical events (OR: 15.7; 95% CI: 4.15-133.7; P = 0.031). CONCLUSIONS: cTnI on admission may improve risk assessment of patients undergoing open surgical embolectomy due to acute PE.

Chick ex ovo culture and ex ovo CAM assay: how it really works.

Chicken eggs in the early phase of breeding are between in vitro and in vivo systems and provide a vascular test environment not only to study angiogenesis but also to study tumorigenesis. After the chick chorioallantoic membrane (CAM) has developed, its blood vessel network can be easily accessed, manipulated and observed and therefore provides an optimal setting for angiogenesis assays. Since the lymphoid system is not fully developed until late stages of incubation, the chick embryo serves as a naturally immunodeficient host capable of sustaining grafted tissues and cells without species-specific restrictions. In addition to nurturing developing allo- and xenografts, the CAM blood vessel network provides a uniquely supportive environment for tumor cell intravasation, dissemination, and vascular arrest and a repository where arrested cells extravasate to form micro metastatic foci. For experimental purposes, in most of the recent studies the CAM was exposed by cutting a window through the egg shell and experiments were carried out in ovo, resulting in significant limitations in the accessibility of the CAM and possibilities for observation and photo documentation of effects. When shell-less cultures of the chick embryo were used(1-4), no experimental details were provided and, if published at all, the survival rates of these cultures were low. We refined the method of ex ovo culture of chick embryos significantly by introducing a rationally controlled extrusion of the egg content. These ex ovo cultures enhance the accessibility of the CAM and chick embryo, enabling easy in vivo documentation of effects and facilitating experimental manipulation of the embryo. This allows the successful application to a large number of scientific questions: (1) As an improved angiogenesis assay(5,6), (2) an experimental set up for facilitated injections in the vitreous of the chick embryo eye(7-9), (3) as a test environment for dissemination and intravasation of dispersed tumor cells from established cell lines inoculated on the CAM(10-12), (4) as an improved sustaining system for successful transplantation and culture of limb buds of chicken and mice(13) as well as (5) for grafting, propagation, and re-grafting of solid primary tumor tissue obtained from biopsies on the surface of the CAM(14). In this video article we describe the establishment of a refined chick ex ovo culture and CAM assay with survival rates over 50%. Besides we provide a step by step demonstration of the successful application of the ex ovo culture for a large number of scientific applications.