Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

Risk Factor Analysis for 30-day Mortality After Surgery for Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) remains a challenging disease associated with high mortality. Several scores have been suggested to assess surgical risk. None was sufficiently adequate. We therefore analyzed risk factors for 30-day mortality. METHODS: A total of 438 consecutive patients had surgery for IE in our department between 2002 and 2020. Patients were divided into two groups, one consisting of 30-day survivors (362 patients; 82.6%) and one of nonsurvivors (76 patients; 17.4%). Logistic regression analysis on pre- and intraoperative risk factors was performed and the groups were compared by univariable analyses. RESULTS: Patients in mortality group were older (69 [58, 77] vs. 63 [50, 72] years; p < 0.001), EuroSCORE II was higher (24.5 [12.1, 49.0] vs. 8.95 [3.7, 21.2]; p < 0.001) and there were more females. More frequently left ventricular function (below 30%), preoperative acute renal insufficiency, chronic dialysis, insulin-dependent diabetes mellitus, NYHA-class IV (New York Heart Association heart failure class IV), and cardiogenic shock occurred. Patients in the mortality group were often intensive care unit patients (40.8 vs. 22.4%; p < 0.001) or had a preoperative stroke (26.3 vs. 16.0%; p = 0.033). In the nonsurvivor group Staphylococcus aureus was prevalent. Streptococcus viridans was common in the survivor group as was isolated aortic valve endocarditis (32.9 vs. 17.1%; p = 0.006). Prosthetic valve endocarditis (PVE) and abscesses occurred more often in nonsurvivors. In the logistic regression analysis, female gender, chronic dialysis, cardiogenic shock, and NYHA IV and from intraoperative variables PVE, cardiopulmonary bypass time, and mitral valve surgery were the strongest predictors for 30-day mortality. CONCLUSION: This study indeed clearly indicates that significant risk factors for 30-day mortality cannot be changed. Nevertheless, they should be taken into account for preoperative counselling, and they will alert the surgical team for an even more careful management.

Impact of Diabetes in Patients With Acute Myocardial Infarction Undergoing Coronary Artery Bypass Surgery Within 48 Hours.

BACKGROUND: Diabetic patients with coronary artery disease may benefit from elective coronary artery bypass graft (CABG) surgery. It is unknown whether this merit is transferable to patients with acute myocardial infarction (AMI) undergoing surgery. METHOD: A total of 1,427 patients underwent CABG within 48 hours of being diagnosed with AMI at the current institution between 2001 and 2019. Of these patients, 206 (14.4%) had insulin-dependent diabetes mellitus (IDDM) and 148 (10.4%) had non-insulin dependent diabetes mellitus (NIDDM). Retrospective data analysis was performed. RESULTS: Patients with NIDDM showed the highest perioperative risk profile, with a EuroScore II of 11.6 (±10.3) compared with 7.8 (±8.0) in non-diabetic patients and 8.4 (±7.8) in patients with IDDM (p<0.001). Sub-analysis demonstrated a higher proportion of non-ST-elevation myocardial infarction patients in the NIDDM cohort compared with the IDDM cohort (70.9% vs 56.8%; p=0.005). Postoperatively, NIDDM patients had more sepsis (p<0.01) and longer ventilation times (p<0.001) compared with non-DM and IDDM patients (p<0.01). Wound healing complications were rare, but almost twice as high in NIDDM patients compared with non-DM and IDDM patients (4.7% vs 0.9% vs 2.4%, respectively). The 30-day mortality was highest in the NIDDM cohort (18.3% vs 11.3% vs 7.8%; p=0.012). Analysis of survival for up to 15 years revealed a significantly reduced survival of diabetic patients compared with non-diabetic patients, with lowest survival rates in NIDDM patients (p<0.001). CONCLUSIONS: Non-insulin dependent diabetes mellitus patients undergoing CABG within 48 hours of being diagnosed with AMI are at increased risk of short-term and long-term complications. Therefore, this particular group should undergo a careful evaluation concerning the expected risks and benefits of CABG in this setting.

Characterization of large extracellular vesicles (L-EV) derived from human regulatory macrophages (Mreg): novel mediators in wound healing and angiogenesis?

BACKGROUND: Large extracellular vesicles (L-EV) with a diameter between 1 and 10 µm are released by various cell types. L-EV contain and transport active molecules which are crucially involved in cell to cell communication. We have shown that secretory products of human regulatory macrophages (Mreg) bear pro-angiogenic potential in-vitro and our recent findings show that Mreg cultures also contain numerous large vesicular structures similar to L-EV with so far unknown characteristics and function. AIM OF THIS STUDY: To characterize the nature of Mreg-derived L-EV (L-EVMreg) and to gain insights into their role in wound healing and angiogenesis. METHODS: Mreg were differentiated using blood monocytes from healthy donors (N = 9) and L-EVMreg were isolated from culture supernatants by differential centrifugation. Characterization of L-EVMreg was performed by cell/vesicle analysis, brightfield/transmission electron microscopy (TEM), flow cytometry and proteome profiling arrays. The impact of L-EVMreg on wound healing and angiogenesis was evaluated by means of scratch and in-vitro tube formation assays. RESULTS: Mreg and L-EVMreg show an average diameter of 13.73 ± 1.33 µm (volume: 1.45 ± 0.44 pl) and 7.47 ± 0.75 µm (volume: 0.22 ± 0.06 pl) respectively. Flow cytometry analyses revealed similarities between Mreg and L-EVMreg regarding their surface marker composition. However, compared to Mreg fewer L-EVMreg were positive for CD31 (P < 0.01), CD206 (P < 0.05), CD103 (P < 0.01) and CD45 (P < 0.05). Proteome profiling suggested that L-EVMreg contain abundant amounts of pro-angiogenic proteins (i.e. interleukin-8, platelet factor 4 and serpin E1). From a functional point of view L-EVMreg positively influenced in-vitro wound healing (P < 0.05) and several pro-angiogenic parameters in tube formation assays (all segment associated parameters, P < 0.05; number of meshes, P < 0.05). CONCLUSION: L-EVMreg with regenerative and pro-angiogenic potential can be reproducibly isolated from in-vitro cultured human regulatory macrophages. We propose that L-EVMreg could represent a putative therapeutic option for the treatment of chronic wounds and ischemia-associated diseases.

Repetitive application of remote ischemic conditioning (RIC) in patients with peripheral arterial occlusive disease (PAOD) as a non-invasive treatment option: study protocol for a randomised controlled clinical trial.

BACKGROUND: The best medical treatment (BMT) for most patients with early stage of peripheral arterial occlusive disease (PAOD) is often limited to gait training and pharmacological therapy besides endovascular surgery. The application of remote ischemic conditioning (RIC) has been described as a promising experimental strategy for the improvement of therapeutic outcome in cardiovascular disease but has not proven beneficial effects in clinical practice and treatment of PAOD yet. METHODS: Here we describe a prospective, randomized trial for the evaluation of possible effects of repeated application of RIC in patients with PAOD. This monocentric study will enrol 200 participants distributed to an intervention group receiving RIC + BMT and a control group only receiving BMT for four weeks. Patients are at least 18 years of age and have diagnosed PAOD Fontaine stage II b. Pain-free and total walking distance will be measured via treadmill test (primary endpoints). In addition, ankle-brachial index (ABI) and quality of life (QoL) will be assessed using the SF-36 and VascuQoL-6 questionnaire. Moreover, evaluation of markers for atherosclerosis, angiogenic profiling and mononuclear cell characterization will be performed using biochemical assays, proteome profiling arrays and flow cytometry (secondary endpoints). DISCUSSION: Our prospective, randomized monocentric trial is the first of its kind to analyse the effects of chronic and repetitive treatment with RIC in patients with PAOD and might provide important novel information on the molecular mechanisms associated with RIC in PAOD patients. TRIAL REGISTRATION: Prospectively registered in the German Clinical Trials Register (Deutsche Register Klinischer Studien) Registration number: DRKS00025735; Date of registration: 01.07.2021.

Acquired von Willebrand syndrome in ECMO patients: A 3-year cohort study.

BACKGROUND: Bleeding is a common but possibly underreported side effect of Extracorporeal Membrane Oxygenation (ECMO). Impairment of primary hemostasis by acquired von Willebrand syndrome (aVWS) and platelet dysfunction as well as activation and consumption of plasmatic coagulation factors contribute to hemorrhage. The aim of the present cohort study of consecutively enrolled patients admitted to our ECMO center was to collect demographic, medical and laboratory data possibly associated with i) development of clinically relevant bleeding and/or ii) death during a 12-months follow-up. RESULTS: Within a 3-year period 338 white patients aged 18-89 years (median: 60; male 64.5%) were enrolled. 78 of 338 patients (23%) presented with clinical relevant bleeding symptoms. The overall death rate was 74.6% within a median time of 9 days (1-229) post intervention. Logistic-regression analysis adjusted for age and gender revealed that i) the presence of blood group O versus non-O (Odds ratio (OR)/95%CI: 1.9/1.007-3.41), ECMO duration per day (1.1/1.06-1.14), veno-venous versus veno-arterial ECMO cannulation (2.33/1.2-4.5) and the overall need for blood product administered per unit (1.02/1.016-1.028) was independenly associated with bleeding in patients suffering from aVWS. ii) Older age (increase per year) at ECMO start (1.015/1.012-1.029) and an increasing amount of blood product units were significantly related with death (1.007/1.001-1.013). Patients with veno-venous versus veno-arterial cannulation survived longer (0.48/0.24-0.94). CONCLUSION: In the present cohort study we found a clinical relevant bleeding rate of 23% in subjects with aVWS associated with blood group O, a longer ECMO duration and veno-venous cannulation.

Sexual Dysfunction Before and after Treatment of Infrarenal Aortic Aneurysm Patients.

OBJECTIVE: Sexual dysfunction is supposed to be one major complication after treatment of infrarenal aortic aneurysms. It is still controversial how many patients suffer from a sexual dysfunction already before their operation and if there are any procedure-specific differences in postoperative sexual function depending on the operative procedure performed, for example, open (OAR) or endovascular aortic repair (EVAR). METHODS: To answer these questions we conducted this prospective unicentric study using the International Index of Erectile Function (IIEF) and analyzed the sexual function of 56 male patients with an infrarenal aortic aneurysm before as well as 3, 6, and 12 months after their operation. 23 patients (median age 66.5 years) were treated by OAR and 33 patients (median age 75.8 years) by EVAR. RESULTS: We observed that the majority of the 56 patients analyzed (91.3% of the 23 OAR patients and 96.8% of the 33 EVAR patients) suffered from a sexual dysfunction already before their operation. A 56.5% of the OAR patients and 67.7% of the EVAR patients even disclaimed a severe sexual dysfunction prior to surgery. Age and operation method showed no significant influence on the IIEF score (P= 0.647 and P= 0.621, respectively). The change of the IIEF score over the 4 time points also did not significantly differ for age and operation method (P= 0.713 and P= 0.624, respectively). The IIEF scores were significantly different between time points T1 and T4 (P= 0.042), whereas between the other time points no significant differences were found. CONCLUSIONS: Sexual dysfunction is very common in infrarenal aortic aneurysm patients even before their operation. OAR and EVAR do not cause a procedure-specific deterioration of the sexual function.

Risk Factors for Mortality in Acute Aortic Dissection Type A: A Centre Experience Over 15 Years.

INTRODUCTION: Acute aortic dissection Type A (AADA) is still associated with a high mortality rate and frequent postoperative complications. This study was designed to evaluate the risk factors for mortality in AADA patients. PATIENTS AND METHODS: This retrospective analysis included 344 consecutive patients who underwent surgery for AADA in moderate hypothermic circulatory arrest (20-24°C nasopharyngeal) between 2001 and 2016. RESULTS: The 30-day mortality rate was 18%. Nonsurvivors were significantly older (65.7 ± 12.0 years vs. 62.0 ± 12.5 years; p = 0.034) with significantly higher Euro-score II [15.4% (6.6; 23.0) vs. 4.63% (2.78; 9.88); p < 0.001)]. Intraoperatively, survivors had statistically shorter cardiopulmonary bypass times [163 (134; 206) vs. 198 min (150; 245); p = 0.001]. However, the hypothermic circulatory arrest time was similar between both groups. Postoperatively, the incidence of acute kidney injury (AKI) (55.9 vs. 15.2%; p < 0.001), stroke (27.9 vs. 12.1%; p = 0.002) and sepsis (18.0 vs. 2.1%; p < 0.001) were significantly higher among nonsurvivors. The multi-variable logistic regression confirmed that older age, previous cardiac surgery, preoperative cardiopulmonary resuscitation (CPR), blood transfusion and postoperative acute kidney injury (AKI) were independent risk factors for mortality. CONCLUSION: Our analysis suggested that the reason for mortality was multifactorial, especially age, previous cardiac surgery, CPR, transfusion, as well as postoperative AKI were considered risk factors for mortality.

Sex-Specific Outcome after Ascending Aortic Surgery in Moderate Hypothermic Circulatory Arrest.

BACKGROUND: Historically, female patients had worse outcome undergoing heart surgery. No recent data exist on gender-specific outcome after moderate hypothermic circulatory arrest (MHCA). The aim of this large retrospective analysis was to investigate gender disparity in patients undergoing elective surgery of ascending aorta in MHCA at 24°C. METHODS: We conducted a retrospective review of 905 (33.3% female) cases of elective heart surgery in MHCA for ascending aortic aneurysm (90.9%) or severely calcified aorta (12.5%) between 2001 and 2015. Furthermore, 299 female and 299 male patients matched by propensity score were compared. Patients with dissection of the aorta were excluded. RESULTS: Women were older (68.4 ± 9.9 vs. 65.8 ± 11.6 years; p = 0.002), had higher logistic EuroSCORE I (18.4 [11.7; 29.2] vs. 12.3% [7.4; 22.6]; p < 0.001), and significantly shorter cardiopulmonary bypass (CPB) time (132 [105; 175] vs. 150 [118; 192] minutes; p < 0.001), while mean MHCA time was longer (15 [13; 19] vs. 14 [12; 17] minutes; p = 0.003). Surgical procedures were less complex in women and they were treated more frequently by isolated supracoronary ascending aorta replacement (61 vs. 54%; p = 0.046). Postoperatively, men showed a higher incidence of neurologic complications (7.0 vs. 3.3%; p = 0.03). The 30-day mortality (women 4.9% vs. men 3.9%; p = 0.48) did not differ significantly, likewise after statistical matching (4.7 vs. 2.3%; p = 0.120). Age, CPB time, and blood transfusion, but not female gender, were risk factors for mortality in multivariable regression analysis. CONCLUSION: This study supports the hypothesis that female gender is not associated with increased short-term mortality or perioperative adverse events in elective aortic surgery in MHCA.

Impact of a surgical approach for implantation of durable left ventricular assist devices in patients on extracorporeal life support.

BACKGROUND: The aim of this study was to evaluate the impact of the surgical approach on the postoperative outcome in patients who underwent left ventricular assist device (LVAD) implantation after having received veno-arterial extracorporeal life support (va-ECLS) using data from a European registry (ECLS-VAD). Five hundred and thirty-one patients were included. METHODS: A propensity score-adjusted outcome analysis was performed, resulting in 324 patients in the full sternotomy (FS) group and 39 in the less invasive surgery (LIS) group. RESULTS: The surgery lasted in median 236 min in the FS group versus 263 min in the LIS group (p = 0.289). The median chest tube output during the first 24 h was similar in both groups. Patients who underwent implantation with an FS required more blood products during the first 24 postoperative hours (median 16 vs. 12, p = 0.033). The incidence of revision due to bleeding was also higher (35.5 vs. 15.4%, p = 0.016). A temporary postoperative right ventricular assist device was necessary in 45.1 (FS) versus 23.1% (LIS) of patients, respectively (p = 0.067). No stroke occurred in the LIS group during the first 30 days after surgery (7.4% in the FS group). The incidence of stroke and of renal, hepatic, and respiratory failure during the follow-up was similar in both groups. The 30-day and one-year survival were similar in both groups. CONCLUSION: LIS for implantation of a durable LVAD in patients on va-ECLS implanted for cardiogenic shock is associated with less revision due to bleeding, less administration of blood products and absence of perioperative stroke, with no impact on survival.

Effectiveness and Safety of Percutaneous Thrombectomy Devices: Comparison of Rotarex and Angiojet in a Physiological Circulation Model.

OBJECTIVE: To compare the percutaneous Rotarex and Angiojet thrombectomy devices with regard to effectiveness and in vitro safety. METHODS: The Rotarex and Angiojet devices were evaluated in an established in vitro pulsatile flow model with a human femoropopliteal vessel phantom. First pass recanalisation and thrombus weight were assessed after thrombectomy, as well as micro- and macro-emboli. Further, histological evaluation of the vascular phantom was performed to analyse vascular injuries. RESULTS: Thrombus weight did not differ significantly prior to the thrombectomy between the groups, but the Rotarex showed slight advantages in thrombus removal vs. the Angiojet regarding first pass recanalisation. Micro- and macro-emboli occurred in most of the endovascular manoeuvres performed; however, significantly more macro-emboli (2.37 ± 1.51 vs. 0.87 ± 0.83; p = .048) were observed using the Rotarex than the Angiojet. Macroscopic dissections were detected in the Rotarex group (n = 3) but not in the Angiojet group. Microscopic vascular injuries were detected significantly more often in the Rotarex group (Rotarex: 531.61 µm ± 102.81 µm; Angiojet: 705.42 µm ± 61.68 µm [p = .001]). CONCLUSION: Both devices showed a comparable performance, with a slight advantage for the Rotarex regarding first pass recanalisation. Significantly more thrombo-emboli, and vascular injuries were observed in the Rotarex group with the latter being obviously the more tissue preserving procedure but potentially with a lower rate of recanalisation. Based on the present results, clinical randomised trials, including long term follow up, are needed to optimise and improve the use of catheter based procedures, taking into account the thrombus entity, localisation, and clinical history.

Impact of Patient-Prosthesis Mismatch following Aortic Valve Replacement on Long-Term Survival and Quality of Life.

BACKGROUND: The impact of patient-prosthesis mismatch (PPM) after aortic valve replacement (AVR) on long-term survival and quality of life (QoL) remains controversial. The objective of this study was to evaluate the impact of PPM on long-term survival and QoL in a large cohort of patients treated with isolated stented biological AVR in a single-center experience. METHODS: We analyzed data of 632 consecutive patients following isolated stented biological AVR between 2007 and 2012 at our institution. We evaluated the QoL (393 evaluable patients) using the Short Form 12-item Health Survey (SF-12) questionnaire via telephone call and the impact of PPM on long-term survival (533 evaluable patients) by Kaplan-Meier's estimate. RESULTS: Severe PPM (<0.65 cm2/m2) had a negative impact on physical component summary (PCS) score (SF-12) compared with patients with moderate or no PPM (p = 0.014), while the mental component summary (MCS) score (SF-12) was not affected by the degree of PPM (p = 0.133). Long-term survival was not different among the three different PPM groups investigated (p = 0.75). CONCLUSION: Severity of PPM demonstrated no influence on long-term survival and MCS score (SF-12), but it was associated with a lower PCS score (SF-12) in patients with severe PPM.

Severe Calcification of the Ascending Aorta Detected Incidentally in Patients Undergoing Cardiac Surgery.

BACKGROUND: Incidentally discovered severe calcified ascending aorta (CAA) is a major challenge faced by surgeons during cardiac surgery. The aim of this study was to evaluate the outcome in patients undergoing cardiac surgery in this condition with the additional replacement of the CAA. METHODS: A retrospective study on a cohort of 74 patients (28.4% females; mean age: 73 ± 7 years) underwent cardiac surgery and initial replacement of an incidentally discovered CAA using moderate hypothermic circulatory arrest. A control group was matched according to age, gender, and procedure. RESULTS: No significant differences were noted with regard to preoperative risk factors. Due to the additional replacement of CAA, the extracorporeal circulation and cross-clamping time were significantly longer in the study group (p < 0.001). Postoperatively, no significant differences in complications were observed between the groups. There was no significant difference in regard to incidence of neurologic adverse events (5.4 vs. 2.7%; p = 0.68) or 30-day mortality (6.7 vs. 4.1%; p = 0.72). CONCLUSION: Our study showed that the initial replacement of incidental CAA in patients undergoing cardiac surgery was not associated with increased risks for neurologic adverse events and mortality.

Randomized trial of ticagrelor vs. aspirin in patients after coronary artery bypass grafting: the TiCAB trial.

AIMS: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. METHODS AND RESULTS: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53). CONCLUSION: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. CLINICALTRIALS.GOV IDENTIFIER: NCT01755520.

Remote ischemic preconditioning attenuates intestinal mucosal damage: insight from a rat model of ischemia-reperfusion injury.

BACKGROUND: Remote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia-reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury. METHODS: Thirty rats were randomly assigned to four groups: I/R; I/R + RIPC; Sham; Sham + RIPC. Animals were anesthetized and the superior mesenteric artery was clamped for 30 min, followed by 60 min of reperfusion. RIPC-treated rats received 3 × 5 min of bilateral hindlimb I/R prior to surgery, sham groups obtained laparotomy without clamping. After I/R injury serum/tissue was analyzed for: Mucosal damage, Caspase-3/7 activity, expression of cell stress proteins, hydrogen peroxide (H2O2) and malondialdehyde (MDA) production, Hypoxia-inducible factor-1α (HIF-1α) protein expression and matrix metalloproteinase (MMP) activity. RESULTS: Intestinal I/R resulted in increased mucosal injury (P < 0.001) and elevated Caspase-3/7 activity (P < 0.001). RIPC significantly reduced the histological signs of intestinal I/R injury (P < 0.01), but did not affect Caspase-3/7 activity. Proteome profiling suggested a RIPC-mediated regulation of several cell stress proteins after I/R injury: Cytochrome C (+ 157%); Cited-2 (- 39%), ADAMTS1 (+ 74%). Serum concentrations of H2O2 and MDA remained unchanged after RIPC, while the reduced intestinal injury was associated with increased HIF-1α levels. Measurements of MMP activities in serum and intestinal tissue revealed an attenuated gelatinase activity at 130 kDa within the serum samples (P < 0.001) after RIPC, while the activity of MMPs within the intestinal tissue was not affected by I/R injury or RIPC. CONCLUSIONS: RIPC ameliorates intestinal I/R injury in rats. The underlying mechanisms may involve HIF-1α protein expression and a decreased serum activity of a 130 kDa factor with gelatinase activity.

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

BACKGROUND: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. METHODS: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. RESULTS: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS. CONCLUSIONS: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery.

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).

Over Ten Years of Experience with a Modified Right Atrial Anastomosis in Orthotopic Heart Transplantation: Follow-up and Comparison with the Biatrial and Bicaval Technique.

BACKGROUND: In 1997, a modified right atrial anastomosis (cavoatrial technique) for orthotopic heart transplantation (oHTx) was first developed in our institution. The purpose of this study is to report our long-term experience with this technique compared with biatrial and bicaval technique. METHODS: Retrospectively, 202 consecutive oHTx between 1997 and 2013 were analyzed. The applied transplantation techniques were biatrial (n = 108), bicaval (n = 22), and cavoatrial (n = 72). RESULTS: Demographic data were similar in all groups. The cardiopulmonary bypass and cross-clamp time were significantly shorter in the biatrial group. Follow-up echocardiographic examination showed excellent results in all groups with no relevant differences. After 1 year, occurrence of severe tricuspid regurgitation (biatrial 1.9% vs bicaval 0.0% vs cavoatrial 1.4%) was low in all groups. Rate of permanent pacemaker implantations was also low (12.0% vs 5.0% vs 11.1%). There were no significant differences in survival between the groups. CONCLUSION: The cavoatrial technique can be a safe and simple alternative for heart transplantation. Easy handling and similar reduced postoperative complications encourage the use of this technique.

Development of a new catheter prototype for laser thrombolysis under guidance of optical coherence tomography (OCT): validation of feasibility and efficacy in a preclinical model.

In this feasibility study, a novel catheter prototype for laser thrombolysis under the guidance of optical coherence tomography (OCT) was designed and evaluated in a preclinical model. Human arteries and veins were integrated into a physiological flow model and occluded with thrombi made from the Chandler Loop. There were four experimental groups: placebo, 20 mg alteplase, laser, 20 mg alteplase + laser. The extent of thrombolysis was analyzed by weighing, OCT imaging and relative thrombus size. In the alteplase group, thrombus size decreased to 0.250 ± 0.036 g (p < 0.0001) and 14.495 ± 0.526 mm2 (p < 0.0001) at 60 min. The relative thrombus size decreased to 73.6 ± 4.1% at 60 min (p < 0.0001). In the laser group, thrombus size decreased significantly to 0.145 ± 0.028 g (p < 0.0001) and 11.559 ± 1.034 mm2 (p < 0.0001). In the alteplase + laser group, thrombus size decreased significantly (0.051 ± 0.026 g; p < 0.0001; 9.622 ± 0.582 mm2; p < 0.0001; 47.4 ± 6.1%; p < 0.0001) in contrast to sole alteplase and laser application. The reproducibility and accuracy of the OCT imaging was high (SD <10%). Histological examination showed no relevant destruction of the vascular layers after laser ablation (arteries: 745.8 ± 5.5 µm; p = 0.69; veins: 448.3 ± 4.5 µm; p = 0.27). Thus, laser ablation and OCT imaging are feasible with the novel catheter and thrombolysis combining alteplase with laser irradiation appears highly efficient.

Impact of Gender on Outcome in Octogenarians after Coronary Artery Bypass Grafting.

Background Increasing life expectancy makes cardiac surgery in octogenarians not very uncommon. In this study, the impact of gender on outcome of octogenarians after coronary artery bypass grafting (CABG) was assessed. Materials and Methods We retrospectively studied 485 octogenarians (176 females: mean age 82.4 ± 2.2 years vs. 306 males: mean age 82.2 ± 2.4 years) who underwent isolated CABG using extracorporeal circulation between January 2005 and December 2012. Results No significant differences were noted between both gender groups with regard to preoperative risk factors. At baseline, the groups differed significantly with respect to mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (women: 22.3 ± 17.4% vs. men: 17.5 ± 13.3%; p < 0.001). Likewise, EuroSCORE II differs significantly between women and men in our cohort (women: 16.7 ± 11.9% vs. men: 13.9 ± 10.7%; p = 0.008). Intraoperatively, the number of distal anastomoses (3.1 ± 0.9 vs. 3.2 ± 0.8), the mean extracorporeal circulation time (99 ± 31 vs. 102 ± 29 minutes), and the mean aortic cross-clamp time (63 ± 31 vs. 60 ± 19 minutes) were similar in both groups. Postoperatively, no significant differences in complications and major morbidity were observed between the groups. The 30-day mortality (women 8.0 vs. men 9.7%; p = 0.62) were without statistical significance between the groups. Conclusion Outcome of octogenarians after CABG resulted in acceptable mortality. Female gender was not associated with increased risks for morbidity and mortality after surgery. Satisfactory outcomes encourage the offering of surgery in octogenarians.