Risk Factors for High Blood Product Use in Patients with Stanford Type A Dissection.

BACKGROUND: Intraoperative and postoperative bleeding associated with allogeneic blood transfusion and reoperation is still a common and feared complication in patients undergoing surgery due to acute Type A Aortic Dissection (aTAAD). The aim of our study was to identify risk factors for higher transfusion rates. METHODS: In this retrospective single center study we evaluated pre -, intra-, and postoperative data of 121 patients with aTAAD. Depending on the median of received packed red blood cells (PRBCs), patients were divided into Group A (<8 PRBC, n = 53) and Group B (≥8 PRBC n = 68). Statistical analyses (descriptive statistics, univariable and multivariable logistic regression) were performed using SPSS software 25.0. Statistical significance was assumed at p-value <0.05. RESULTS: A total of 120 patients received a blood product during their perioperative course. Among others we identified age, hemorrhagic pericardial effusion, and dual antiplatelet therapy as preoperative risk factors, low rectal temperature as intraoperative risk factor and low body temperature, positive fluid balance, high lactate level and beginning development of acute renal failure as postoperative risk factors. CONCLUSION: Our study identifies several factors which predict a higher likelihood of bleeding and consecutive blood transfusion. Knowledge of these factors could influence the therapy to reduce transfusion requirements and lead to a targeted and more efficient use of coagulation products.

Right ventricular assessment in patients undergoing transcatheter or surgical aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative treatment option to surgical aortic valve replacement (SAVR) in selected high-risk patients. In this study, we aimed to evaluate the prognostic value of right ventricular (RV) functional imaging to predict clinical response to TAVR and SAVR. METHODS: One hundred and ten patients with symptomatic severe aortic valve stenosis (AVS) undergoing successful TAVR and 32 controls undergoing SAVR were prospectively enrolled. Six months follow up (FU) included two-dimensional (2D) transthoracic echocardiography (TTE) with RV deformation imaging. RESULTS: Baseline TTE showed no significant differences between groups (TAVR and SAVR) in conventional left ventricular (LV) and RV functional parameters (LV ejection fraction [LV-EF]: p = .21; tricuspidal annular plane systolic excursion [TAPSE]: 1.8 ± 0.5 cm, 1.9 ± 0.4 cm, p = .21), and RV strain (right ventricular-global longitudinal strain [RV-GLS] -11.6 ± 5.2%, -11.5 ± 6.5%, p = .70). At FU LV function was unchanged in both groups (p > .05); RV function was significantly improved after TAVR (RV-GLS: -11.6 ± 5.2%, -13.4 ± 6.1%, p = .005; TAPSE: 1.8 ± 0.5 cm, 1.9 ± 0.3 cm, p = .05), and worsened after SAVR (RV-GLS: -11.5 ± 6.5%, -8.9 ± 5.2%, p = .04; TAPSE: 1.9 ± 0.4 cm, 1.5 ± 0.3 cm, p < .001). Functional New York Heart Association (NYHA) class remained unchanged in patients after SAVR (p = .21), and improved after TAVR (p < .001). Baseline RV function was linked with clinical response to TAVR (TAPSE, p < .0001; RV-GLS, p = .04), and the development of RV-GLS was associated with functional worsening after SAVR (p = .05). CONCLUSION: Baseline RV function and changes of right heart mechanics are closely associated with functional improvements after AVR. SAVR, but not TAVR, seems to have detrimental effects on RV-function.

Heart regeneration and the cardiomyocyte cell cycle.

Cardiovascular disease and in particular, heart failure are still main causes of death; therefore, novel therapeutic approaches are urgently needed. Loss of contractile substrate in the heart and limited regenerative capacity of cardiomyocytes are mainly responsible for the poor cardiovascular outcome. This is related to the postmitotic state of differentiated cardiomyocytes, which is partly due to their polyploid nature caused by cell cycle variants. As such, the cardiomyocyte cell cycle is a key player, and its manipulation could be a promising strategy for enhancing the plasticity of the heart by inducing cardiomyocyte proliferation. This review focuses on the cardiac cell cycle and its variants during postnatal growth, the different regenerative responses of the heart in dependance of the developmental stage and on manipulations of the cell cycle. Because a therapeutic goal is to induce authentic cell division in cardiomyocytes, recent experimental approaches following this strategy are also discussed.

Dilatation of Vascular Prostheses in Ascending Aortic Position: A Long-Term Follow-Up Computed Tomography Study with Comparison of Different Measurement Methods.

BACKGROUND: The aim of this study was to evaluate long-term dilatation of Hemashield Gold and Hemashield Platinum vascular prostheses in ascending aortic position using different measurement methods to obtain precise results. METHODS: Between 1999 and 2007, 73 patients with Stanford type A dissection received ascending aortic replacement with Hemashield Gold and Hemashield Platinum prostheses. Measurements were performed using multiplanar reconstruction mode of electrocardiogram (ECG)-gated, multislice spiral computed tomography (MSCT) in strictly orthogonal cross-sectional planes. Different methods of measurement were compared and maximum dilatation was estimated for different time spans. RESULTS: Diameters calculated from the measured circumference showed a significant (p = 0.037) but clinically not relevant difference (0.1 mm) to the mean between the largest and the shortest cross-sectional diameter of the prosthesis. Dilatation after 24.2 ± 10.2 months was 8.5 ± 4.5%. Long-term dilatation after 91.8 ± 34 months amounted to 11.8 ± 4.2%. CONCLUSION: Based on ECG-gated MSCT images, the presented methods of measurement provided reliable results. Long-term analysis shows low dilatation rates for Hemashield prostheses, which therefore can be considered as safe from this point of view. Nevertheless, a maximal dilatation of 20% could be relevant in valve sparing root replacement. It remains unclear if a dilatation like this contributes to the formation of suture aneurysms.

New Mitral Annuloplasty Ring Enables Oversizing of Transcatheter Heart Valve and Prevents Central or Paravalvular Leakage.

Background Transcatheter valve-in-ring strategies have been developed to treat recurrent mitral regurgitation (MR) after failing surgical annuloplasty. However, suboptimal THV expansion with consecutive paravalvular leakage (PVL) is a procedure-immanent issue. Methods A rigid, saddle-shaped ring was cut at four locations. The segments were reconnected with pull-springs, rearranged to the original shape, and covered with a sewing cuff. The length of the annuloplasty ring construct, including extended pull-springs, was defined by the perimeter of an appropriate THV. We deployed a Sapien XT within the new ring, expanded it to its maximum extent, and investigated the geometrical changes. Results Fluoroscopy confirmed oval, saddle-shaped ring before dilation. After THV implantation, the ring segments spread apart and pull-springs were stretched. The extended ring changed its configuration from "oval" to "round" and anchored the THV leaving no paravalvular or central gaps as potential source for PVL. Conclusion We developed an expandable annuloplasty ring that is perfectly concerted to THV implantation. This proof-of-concept study revealed no PVL and good oversizing ability that might impact future annuloplasty ring design. Further studies have to evaluate durability and device safety.

Long-Term Outcome and Quality of Life in Aortic Type A Dissection Survivors.

BACKGROUND: Aortic dissection is a severe and sophisticated disease that is often linked with a number of possible complications. Our study concerns with long-term outcome and quality of life (QoL) in acute aortic dissection type A (AADA) survivors. METHODS: From January 1999 until December 2006, 120 consecutive patients with AADA received an emergency operation. Of the total number of patients, 84 were males (70.0%) and 36 females (30.0%), mean aged 59.8 ± 12 years with a mean follow-up (FU) of 99.2 ± 6 months. RESULTS: Overall mortality was 39.1% during the observational period with a maximum of 156 months. SF-36 observation showed a significant decay in both Physical Component Summary (PCS) and Mental Component Summary (MCS) in FUII (PCS = 38.4) versus FUI (PCS = 43.4, p = 0.013). CONCLUSION: With ongoing postoperative time, patients did not recover but instead have got worse in terms of QoL. The decrease in MCP and linked subscores is an underestimated factor in QoL and long-term outcome after AADA. This is especially true in younger patients, which are judged to compensate better than older patients.

German Heart Surgery Report 2015: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

On the basis of a long-standing voluntary registry, which was founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS), well-defined data of all heart, thoracic, and vascular surgery procedures performed in 78 German heart surgery departments during 2015 are analyzed. In 2015, a total of 103,967 heart surgery procedures (implantable cardioverter defibrillator, pacemaker, and extracardiac procedures without ECC excluded) were submitted to the database. Approximately 14.8% of the patients were at least 80 years old, resulting in an increase of 0.6% compared with the data of 2014. For 38,601 isolated coronary artery bypass grafting procedures (relationship on-/off-pump: 5:1), the unadjusted inhospital mortality was 2.7%. Concerning the 32,346 isolated heart valve procedures (including 10,606 catheter-based implantations) an unadjusted inhospital mortality of 4.4% was observed.This annual updated registry of the GSTCVS represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, demonstrates advancements in heart medicine, and enables internal/external quality assurance for all participants. In addition, the registry demonstrates that the provision of heart surgery in Germany is appropriate and patients are treated nationwide in a round-the-clock service.

Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice.

Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT(-/-))-mice (n = 8-10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT(-/-)-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2(-/-)-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT(-/-)-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2(-/-)-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling.

Risk scores and biomarkers for the prediction of 1-year outcome after transcatheter aortic valve replacement.

BACKGROUND: Up to 50% of the patients still die or have to be rehospitalized during the first year after transcatheter aortic valve replacement (TAVR). This emphasizes the need for more strategic patient selection. The aim of this prospective observational cohort study was to compare the prognostic value of risk scores and circulating biomarkers to predict all-cause mortality and rehospitalization in patients undergoing TAVR. METHODS: We calculated the hazard ratios and C-statistics (area under the curve [AUC]) of 4 risk scores (logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE], EuroSCORE II, Society of Thoracic Surgeons predicted risk of mortality, and German aortic valve score) and 5 biomarkers of inflammation and/or myocardial dysfunction (high-sensitivity C-reactive protein, growth differentiation factor (GDF)-15, interleukin-6, interleukin-8, and N-terminal pro-B-type natriuretic peptide) for the risk of death (n = 80) and the combination of death or rehospitalization (n = 132) during the first year after TAVR in 310 consecutive TAVR patients. RESULTS: The EuroSCORE II and GDF-15 had the strongest predictive value for 1-year mortality (EuroSCORE II, AUC 0.711; GDF-15, AUC 0.686) and for the composite end point (EuroSCORE II, AUC 0.690; GDF-15, AUC 0.682). When added to the logistic EuroSCORE and EuroSCORE II, GDF-15 enhanced the prognostic performance of the score and enabled substantial reclassification of patients. Combinations of increasing tertiles of the logistic EuroSCORE or EuroSCORE II and GDF-15 allowed the stratification of the patients into subgroups with mortality rates ranging from 4.0% to 49.1% and death/rehospitalization rates ranging from 15.3% to 68.4%. CONCLUSIONS: Our study identified GDF-15 in addition to the logistic EuroSCORE and the EuroSCORE II as the most promising predictors of a poor outcome after TAVR.

Retrograde Autologous Priming as a Safe and Easy Method to Reduce Hemodilution and Transfusion Requirements during Cardiac Surgery.

BACKGROUND: During the last decades many efforts have been made to reduce transfusion requirements and adverse clinical effects during cardiopulmonary bypass (CPB). The minimal extracorporeal circulation (MECC) system and the technique of retrograde autologous priming (RAP) of a conventional CPB circuit have been associated with decreased hemodilution. Our study aimed to compare conventional CPB (cCPB), RAP, and the ROCsafe MECC (Terumo Europe N.V., Leuven, Belgium) system in elective coronary artery bypass patients. PATIENTS AND METHODS: Data were retrospectively collected on three cohorts of 30 adult CPB patients. Patients were operated using cCPB, RAP, and the ROCsafe MECC system. RESULTS: The three groups were comparable in demographic data. The priming volume in the ROCsafe and RAP group was significantly less compared with the conventional priming group (p <0.05). The mean time of extracorporeal circulation and aortic cross-clamp time (p <0.05) were significantly shorter in the ROCsafe group. The levels of hemoglobin (Hb) and hematocrit (Hct) during CPB and postoperatively showed significant differences between the three groups (p < 0.05) and resulted in significantly higher blood transfusion requirements (p < 0.05). Lactate, serum creatinine, troponin, and creatine kinase-myocardial band (CK-MB) levels did not differ significantly among the three groups (p >0.05). There was also no statistically significant difference in ventilation time, intensive care unit (ICU) stay, overall hospital stay, and postoperative complications (p >0.05). CONCLUSION: In conclusion, RAP is compared with cCPB and MECC a safe and low-cost technique in reducing the priming volume of the CPB system, causes less hemodilution, and reduces the need for intra- and postoperative blood transfusion.

The German Aortic Valve Registry (GARY): in-hospital outcome.

BACKGROUND: Aortic stenosis is a frequent valvular disease especially in elderly patients. Catheter-based valve implantation has emerged as a valuable treatment approach for these patients being either at very high risk for conventional surgery or even deemed inoperable. The German Aortic Valve Registry (GARY) provides data on conventional and catheter-based aortic procedures on an all-comers basis. METHODS AND RESULTS: A total of 13 860 consecutive patients undergoing repair for aortic valve disease [conventional surgery and transvascular (TV) or transapical (TA) catheter-based techniques] have been enrolled in this registry during 2011 and baseline, procedural, and outcome data have been acquired. The registry summarizes the results of 6523 conventional aortic valve replacements without (AVR) and 3464 with concomitant coronary bypass surgery (AVR + CABG) as well as 2695 TV AVI and 1181 TA interventions (TA AVI). Patients undergoing catheter-based techniques were significantly older and had higher risk profiles. The stroke rate was low in all groups with 1.3% (AVR), 1.9% (AVR + CABG), 1.7% (TV AVI), and 2.3% (TA AVI). The in-hospital mortality was 2.1% (AVR) and 4.5% (AVR + CABG) for patients undergoing conventional surgery, and 5.1% (TV AVI) and AVI 7.7% (TA AVI). CONCLUSION: The in-hospital outcome results of this registry show that conventional surgery yields excellent results in all risk groups and that catheter-based aortic valve replacements is an alternative to conventional surgery in high risk and elderly patients.

The endocannabinoid-CB2 receptor axis protects the ischemic heart at the early stage of cardiomyopathy.

Ischemic heart disease is associated with inflammation, interstitial fibrosis and ventricular dysfunction prior to the development of heart failure. Endocannabinoids and the cannabinoid receptor CB2 have been claimed to be involved, but their potential role in cardioprotection is not well understood. We therefore explored the role of the cannabinoid receptor CB2 during the initial phase of ischemic cardiomyopathy development prior to the onset of ventricular dysfunction or infarction. Wild type and CB2-deficient mice underwent daily brief, repetitive ischemia and reperfusion (I/R) episodes leading to ischemic cardiomyopathy. The relevance of the endocannabinoid-CB2 receptor axis was underscored by the finding that CB2 was upregulated in ischemic wild type cardiomyocytes and that anandamide level was transiently increased during I/R. CB2-deficient mice showed an increased rate of apoptosis, irreversible loss of cardiomyocytes and persistent left ventricular dysfunction 60 days after the injury, whereas wild type mice presented neither morphological nor functional defects. These defects were due to lack of cardiomyocyte protection mechanisms, as CB2-deficient hearts were in contrast to controls unable to induce switch in myosin heavy chain isoforms, antioxidative enzymes and chemokine CCL2 during repetitive I/R. In addition, a prolonged inflammatory response and adverse myocardial remodeling were found in CB2-deficient hearts because of postponed activation of the M2a macrophage subpopulation. Therefore, the endocannabinoid-CB2 receptor axis plays a key role in cardioprotection during the initial phase of ischemic cardiomyopathy development.

German CABG score: a specific risk model for patients undergoing isolated coronary artery bypass grafting.

BACKGROUND: A specific risk model concerning mortality of patients undergoing isolated coronary artery bypass grafting (CABG) is developed based on the national quality benchmarking mandatory by law in Germany. METHODS: On the basis of the national data pool from 2004, a risk score model for patients undergoing isolated CABG was developed and finally adjusted with the data of 43,145 patients of the year 2008. Modeling was performed by logistic regression analysis. This risk model was validated with the 2007 data pool which comprised 45,569 patients. RESULTS: Observed in-hospital mortality after isolated CABG procedures was 3.0% in 2008. Hosmer-Lemeshow test p value was 0.189 and area under receiver operating characteristic curve was 0.826. Applying the German CABG score for 2007 resulted in an observed-to-expected mortality ratio of 1.01. CONCLUSION: The German CABG score for in-hospital mortality is a risk score with proven validity for isolated CABG, developed by means of the patient population in Germany. It can be used for the assessment of patient risk groups and for interhospital benchmarking. We encourage other researchers to apply and validate this score in comparable health care systems.

[Commentary by the German Society for Thoracic and Cardiovascular Surgery on the positions statement by the German Cardiology Society on quality criteria for transcatheter aortic valve implantation (TAVI)]. / Kommentar der Deutschen Gesellschaft für Thorax-, Herz- und Gefäßchirurgie zum Positionspapier der DGK - Qualitätskriterien zur Durchführung der transvaskulären Aortenklappenimplantation (TAVI).

Surgical aortic valve replacement is still considered the first-line treatment for patients suffering from severe aortic valve stenosis. In recent years, transcatheter aortic valve implantation (TAVI) has emerged as an alternative for selected high-risk patients. According to the latest results of the German external quality assurance program, mandatory by law, the initially very high mortality and procedural morbidity have now decreased to approximately 6 and 12%, respectively. Especially in Germany, the number of patients treated by TAVI has increased exponentially. In 2013, a total of 10.602 TAVI procedures were performed. TAVI is claimed to be minimally invasive. This is true concerning the access, but it does not describe the genuine complexity of the procedure, defined by the close neighborhood of the aortic valve to delicate intracardiac structures. Hence, significant numbers of life-threatening complications may occur and have been reported. Owing to the complexity of TAVI, there is a unanimous concordance between cardiologists and cardiac surgeons in the Western world demanding a close heart team approach for patient selection, intervention, handling of complications, and pre- as well as postprocedural care, respectively. The prerequisite is that TAVI should not be performed in centers with no cardiac surgery on site. This is emphasized in all international joint guidelines and expert consensus statements. Today, a small number of patients undergo TAVI procedures in German hospitals without a department of cardiac surgery on site. To be noted, most of these hospitals perform less than 20 cases per year. Recently, the German Cardiac Society (DGK) published a position paper supporting this practice pattern. Contrary to this statement and concerned about the safety of patients treated this way, the German Society for Thoracic and Cardiovascular Surgery (DGTHG) still fully endorses the European (ESC/EACTS) and other actual international guidelines and consensus statements. Only the concomitance of departments for cardiac surgery and cardiology on site can provide optimal TAVI care. This commentary by the DGTHG delineates the data and resources upon which its opinion is based.

Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia.

Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy.

Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium.

Cellular cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which is the most promising cell source. Therefore, we investigated and examined the fate and functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)-derived cardiomyocytes after transplantation into the infarcted mouse heart. This proved particularly challenging for the ES cells, as their enrichment into cardiomyocytes and their long-term engraftment and tumorigenicity are still poorly understood. We generated transgenic ES cells expressing puromycin resistance and enhanced green fluorescent protein cassettes under control of a cardiac-specific promoter. Puromycin selection resulted in a highly purified (>99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6-10-fold because of induction of proliferation on purification. Long-term engraftment (4-5 months) was observed when co-transplanting selected ES cell-derived cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no teratoma formation was found (n = 60). Although transplantation of ES cell-derived cardiomyocytes improved heart function, BM cells had no positive effects. Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell therapy is a promising approach for the treatment of impaired myocardial function and provides better results than BM-derived cells.

Comparison of myocardial remodeling between cryoinfarction and reperfused infarction in mice.

Myocardial infarction is associated with inflammatory reaction leading to tissue remodeling. We compared tissue remodeling between cryoinfarction (cMI) and reperfused myocardial infarction (MI) in order to better understand the local environment where we apply cell therapies. Models of closed-chest one-hour ischemia/reperfusion MI and cMI were used in C57/Bl6-mice. The reperfused MI showed rapid development of granulation tissue and compacted scar formation after 7 days. In contrast, cMI hearts showed persistent cardiomyocyte debris and cellular infiltration after 7 days and partially compacted scar formation accompanied by persistent macrophages and myofibroblasts after 14 days. The mRNA of proinflammatory mediators was transiently induced in MI and persistently upregulated in cMI. Tenascin C and osteopontin-1 showed delayed induction in cMI. In conclusion, the cryoinfarction was associated with prolonged inflammation and active myocardial remodeling when compared to the reperfused MI. These substantial differences in remodeling may influence cellular engraftment and should be considered in cell therapy studies.