Isaac George

Acute kidney injury after aortic valve replacement: incidence, risk factors and outcomes

The occurrence of acute kidney injury (AKI) following aortic valve replacement (AVR) has very serious clinical implications and has therefore been the focus of several studies. The authors report the results of previous studies evaluating both transcatheter AVR (TAVR) and indirectly surgical AVR (SAVR) through looking at cardiopulmonary bypass (CPB) cardiac surgeries, and identify the incidence, predictors and outcomes of AKI following AVR. In most studies, AKI was defined using the Risk, Injury, Failure, Loss and End Stage, Valve Academic Research Consortium (modified Risk, Injury, Failure, Loss and End Stage) or Valve Academic Research Consortium-2 (Acute Kidney Injury Network) AKI classification criteria. Twelve studies including more than 90,000 patients undergoing cardiac surgery on CPB were considered as well as 26 studies with more than 6000 patients undergoing TAVR. Depending on the definition used, AKI occurred in 3.4–43% of SAVR cases with up to 2.5% requiring dialysis, and in 3.4–57% of TAVR cases. Factors identified as independent predictors of AKI were: baseline kidney failure, EUROSCORE, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, anemia, peripheral vascular disease, heart failure, surgical priority, CPB time, reoperation, use of intra-aortic balloon pump, need for re-exploration, contrast agent volume, transapical access, blood transfusion, postoperative thrombocytopenia, postoperative leukocytosis as well as demographic variables such as age and female gender. The 30-day mortality rate for patients with AKI following SAVR ranged from 5.5 to 46% and was 3- to 16-times higher than in those without AKI. Similarly, patients who developed AKI after TAVR had a mortality rate of 7.8–29%, which was two- to eight-times higher than those who did not suffer from AKI. AKI confers up to a fourfold increase in 1-year mortality. Finally, hospital length of stay was significantly increased in patients with AKI in both SAVR and TAVR groups, with increases up to 3- and 2.5–times, respectively.

Del Nido Cardioplegia can be safely administered in high-risk coronary artery bypass grafting surgery after acute myocardial infarction: a propensity matched comparison

ObjectiveDel Nido (DN) cardioplegia solution provides a depolarized hyperkalemic arrest lasting up to 60 minutes, and the addition of lidocaine may limit intracellular calcium influx. Single-dose DN cardioplegia solution may offer an alternative myocardial protection strategy to multi-dose cold whole blood (WB) cardioplegia following acute myocardial infarction (AMI).MethodsWe retrospectively reviewed 88 consecutive patients with AMI undergoing coronary artery bypass (CABG) surgery with cardioplegic arrest between June 2010 to June 2012. Patients exclusively received WB (n = 40, June 2010-July 2011) or DN (n = 48, August 2011-June 2012) cardioplegia. Preoperative and postoperative data were retrospectively reviewed and compared using propensity scoring.ResultsNo significant difference in age, maximum preoperative serum troponin level, ejection fraction, and STS score was present between DN and WB. A single cardioplegia dose was given in 41 DN vs. 0 WB patients (p < 0.001), and retrograde cardioplegia was used 10 DN vs. 31 WB patients (p < 0.001). Mean cardiopulmonary bypass and cross clamp times were significantly shorter in the DN group versus WB group. Tranfusion rate, length of stay, intra-aortic balloon pump requirement, post-operative inotropic support, and 30-day mortality was no different between groups. One patient in the WB group required a mechanical support due to profound cardiogenic shock.ConclusionsDN cardioplegia may provide equivalent myocardial protection to existing cardioplegia without negative inotropic effects in the setting of acute myocardial infarction.

Attenuation of the unfolded protein response and endoplasmic reticulum stress after mechanical unloading in dilated cardiomyopathy

Abnormal intracellular calcium (Ca(2+)) handling can trigger endoplasmic reticulum (ER) stress, leading to activation of the unfolded protein response (UPR) in an attempt to prevent cell death. Mechanical unloading with a left ventricular assist device (LVAD) relieves pressure-volume overload and promotes reverse remodeling of the failing myocardium. We hypothesized that mechanical unloading would alter the UPR in patients with advanced heart failure (HF). UPR was analyzed in paired myocardial tissue from 10 patients with dilated cardiomyopathy obtained during LVAD implantation and explantation. Samples from healthy hearts served as controls. Markers of UPR [binding immunoglobulin protein (BiP), phosphorylated (P-) eukaryotic initiation factor (eIF2α), and X-box binding protein (XBP1)] were significantly increased in HF, whereas LVAD support significantly decreased BiP, P-eIF2α, and XBP1s levels. Apoptosis as reflected by C/EBP homologous protein and DNA damage were also significantly reduced after LVAD support. Improvement in left ventricular dimensions positively correlated with P-eIF2α/eIF2α and apoptosis level recovery. Furthermore, significant dysregulation of calcium-handling proteins [P-ryanodine receptor, Ca(2+) storing protein calsequestrin, Na(+)-Ca(2+) exchanger, sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA2a), ER chaperone protein calreticulin] was normalized after LVAD support. Reduced ER Ca(2+) content as a causative mechanism for UPR was confirmed using AC16 cells treated with a calcium ionophore (A23187) and SERCA2a inhibitor (thapsigargin). UPR activation and apoptosis are reduced after mechanical unloading, which may be mediated by the improvement of Ca(2+) handling in patients with advanced HF. These changes may impact the potential for myocardial recovery.

Increased de novo ceramide synthesis and accumulation in failing myocardium

Abnormal lipid metabolism may contribute to myocardial injury and remodeling. To determine whether accumulation of very long-chain ceramides occurs in human failing myocardium, we analyzed myocardial tissue and serum from patients with severe heart failure (HF) undergoing placement of left ventricular assist devices and controls. Lipidomic analysis revealed increased total and very long-chain ceramides in myocardium and serum of patients with advanced HF. After unloading, these changes showed partial reversibility. Following myocardial infarction (MI), serine palmitoyl transferase (SPT), the rate-limiting enzyme of the de novo pathway of ceramide synthesis, and ceramides were found increased. Blockade of SPT by the specific inhibitor myriocin reduced ceramide accumulation in ischemic cardiomyopathy and decreased C16, C24:1, and C24 ceramides. SPT inhibition also reduced ventricular remodeling, fibrosis, and macrophage content following MI. Further, genetic deletion of the SPTLC2 gene preserved cardiac function following MI. Finally, in vitro studies revealed that changes in ceramide synthesis are linked to hypoxia and inflammation. In conclusion, cardiac ceramides accumulate in the failing myocardium, and increased levels are detectable in circulation. Inhibition of de novo ceramide synthesis reduces cardiac remodeling. Thus, increased de novo ceramide synthesis contributes to progressive pathologic cardiac remodeling and dysfunction.

Acute kidney injury following surgical aortic valve replacement.

Acute kidney injury (AKI) is a significant complication of surgical aortic valve replacement (SAVR). This study sought to describe AKI following SAVR, its risk factors, predictors and effect on long‐term survival.

Reversibility of chronic kidney disease and outcomes following aortic valve replacement

OBJECTIVESnChronic kidney disease (CKD) is prevalent in patients undergoing aortic valve replacement (AVR). We sought to evaluate the impact of AVR on estimated glomerular filtration rate (eGFR) levels and determine the impact of reversibility of CKD on postoperative outcomes.nnnMETHODSnWe retrospectively reviewed 2169 patients who underwent isolated AVR between 2000 and 2012. eGFR was calculated using the CKD-EPI formula. Based on preoperative eGFR, patients were divided into three groups: NoCKD (eGFR >60, n = 1417), ModCKD (eGFR = 30-60, n = 619) and SevCKD (eGFR = 15-30, n = 86). End-stage renal disease patients (eGFR <15 and/or dialysis, n = 47) were excluded from the study.nnnRESULTSnBefore AVR, eGFR in the NoCKD, ModCKD and SevCKD groups was 81.3 ± 14.2, 48.9 ± 8.10 and 25.3 ± 4.12 ml/min/1.73 m(2), respectively. NoCKD patients showed a decline in eGFR during the first month postoperatively; thereafter, eGFR remained stable over 1 year. ModCKD and SevCKD patients demonstrated an initial improvement in eGFR, which peaked at 1 week postoperatively. In ModCKD, eGFR stabilized at a slightly lower level thereafter out to 1-year follow-up. In SevCKD, eGFR declined slightly out to 6 months postoperatively. Regardlessly, eGFR in ModCKD at 1 year and in SevCKD at 6 months postoperatively demonstrated sustained improvement over baseline eGFR. Reversibility of CKD was associated with a better long-term survival in the ModCKD group (P < 0.001) and short-term survival in the SevCKD group (P = 0.018).nnnCONCLUSIONSnAVR confers a marked initial improvement in eGFR, which is sustained in patients with ModCKD and SevCKD, and is associated with a better survival. The reversible nature of CKD in certain patients warrants careful consideration during preoperative risk scoring and stratification.

Rat model of veno-arterial extracorporeal membrane oxygenation

BackgroundWe aim to develop a rat model of veno-arterial extracorporeal membrane oxygenation (VA-ECMO).MethodsVA-ECMO was established in twelve Male Sprague-Dawley rats (250-350xa0g) through cannulation of the right jugular vein for venous drainage and the right femoral artery for arterial reinfusion. Arterial blood pressure was measured using a conductance catheter through cannulation of the left carotid artery. Heart rate was monitored by electrocardiography and arterial blood gas parameters with a blood gas analyzer. The VA-ECMO circuit was tested by subjecting the rats to hypoxic cardiac arrest with resuscitation using VA-ECMO. Both load-dependent and load-independent measures of myocardial contractility were measured using pressure-volume loop analysis to confirm restoration of myocardial function post-resuscitation.ResultsFollowing hypoxic cardiac arrest VA-ECMO provided sufficient oxygenation to support the circulation. The haemodynamic and blood gas parameters were maintained at transition and during ECMO. All animals were resuscitated, regained cardiac function and were able to be weaned off ECMO post-resuscitation.ConclusionWe have established a safe, high-throughput, economical, functioning rat model of VA-ECMO.

Influence of Staphylococcus aureus on Outcomes after Valvular Surgery for Infective Endocarditis

BackgroundAs Staphylococcus aureus (SA) remains one of the leading cause of infective endocarditis (IE), this study evaluates whether S. aureus is associated with more severe infections or worsened outcomes compared to non-S. aureus (NSA) organisms.MethodsAll patients undergoing valve surgery for bacterial IE between 1995 and 2013 at our institution were included in this study (nxa0=xa0323). Clinical data were retrospectively collected from the chart review. Patients were stratified according to the causative organism; SA (nxa0=xa085) and NSA (nxa0=xa0238). Propensity score matched pairs (nxa0=xa064) of SA versus NSA were used in the analysis.ResultsSA patients presented with more severe IE compared to NSA patients, with higher rates of preoperative vascular complications, preoperative septic shock, preoperative embolic events, preoperative stroke, and annular abscess. Among the matched pairs, there were no significant differences in 30-day (9.4% SA vs. 7.8% NSA, ORxa0=xa01.20, pxa0=xa00.76) or 1-year mortality (20.3% SA vs. 14.1% NSA, ORxa0=xa01.57, pxa0=xa00.35) groups, though late survival was significantly worse in SA patients. There was also no significant difference in postoperative morbidity between the two matched groups.ConclusionsSA IE is associated with a more severe clinical presentation than IE caused by other organisms. Despite the clearly increased preoperative risk, valvular surgery may benefit SA IE patients by moderating the post-operative mortality and morbidity.

TCT-674 Sex Specific Outcomes of TAVR with the Sapien 3 Valve: Insights From The PARTNER 2 S3 High-Risk and Intermediate-Risk Cohorts

A survival benefit following transcatheter aortic valvexa0replacement (TAVR) was observed in females as compared to males in inoperable and high-risk patients receiving early generation balloon expandable valves. Whether sex specific outcomes benefit persists in lower risk patients treated with the

Feasibility and safety of continuous retrograde administration of Del Nido cardioplegia: a case series.

BackgroundDel Nido (DN) cardioplegia, a calcium-free, hyperkalemic solution containing lidocaine and magnesium has been developed to help reduce intracellular calcium influx and the resulting myocyte damage in the immediate postischemic period following cardiac arrest. DN cardioplegia has been used for pediatric cardiac surgery but its use in complex reoperative surgery has not been studied. We specifically report the outcomes of patients undergoing reoperative cardiac surgery after previous coronary artery bypass grafting with a patent internal mammary artery (IMA).MethodsPatients undergoing reoperative cardiac surgery with prior coronary bypass grafting surgery were studied between 2010 and 2013. Fourteen patients were identified who required continued retrograde cardioplegia administration. In all cases, an initial antegrade dose was given, followed by continuous retrograde administration. Demographics, co-morbidities, intra-operative variables including cardioplegia volumes, post-operative complications, and patient outcomes were collected.ResultsThe mean age of all patients was 73.3+/−6.7xa0years, and 93xa0% were male. Aortic cross clamp time and cardiopulmonary bypass times were 81+/−35 and 151+/−79 mins, respectively. Antegrade, retrograde and total cardioplegia doses were 1101+/−398, 3096+/−3185 and 4367+/−3751xa0ml, respectively. An average of 0.93+/−0.92 inotropes and 1.50+/−0.76 pressors were used on ICU admission after surgery. ICU and total hospital lengths of stay were 5.5+/−7.4 and 9.6+/−8.0xa0days, respectively. Complications occurred in two patients (14xa0%) (pneumonia and prolonged mechanical ventilation) and new arrhythmias occurred in five patients (36xa0%) (four new-onset atrial fibrillation and one pulseless electrical activity requiring 2xa0min of chest compression). No perioperative myocardial infarctions were noted based on electrocardiograms and cardiac serum markers. Postoperatively, left ventricular function was preserved in all patients whereas two patients (14xa0%) had mild decrease in right ventricular function as assessed by echocardiography. No mortality was observed.ConclusionDel Nido cardioplegia solution provides acceptable myocardial protection for cardiac surgery that requires continuous retrograde cardioplegia administration. DN cardioplegia’s administration in a continuous retrograde fashion with a patent IMA is believed to provide adequate myocardial protection while avoiding injuring the IMA through dissection and clamping.