Predictors and associated clinical outcomes of low cardiac output syndrome following cardiac surgery: insights from the LEVO-CTS trial.

AIMS: High-risk cardiac surgery is commonly complicated by low cardiac output syndrome (LCOS), which is associated with high mortality. There are limited data derived from multi-centre studies with adjudicated endpoints describing factors associated with LCOS and its downstream clinical outcomes. METHODS AND RESULTS: The Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial evaluated prophylactic levosimendan vs. placebo in patients with a reduced ejection fraction undergoing coronary artery bypass grafting (CABG) and/or valve surgery. We conducted a pre-specified analysis on LCOS, which was characterized by a four-part definition. We constructed a multivariable logistical regression model to evaluate risk factors associated with LCOS and performed Cox proportional hazards modelling to determine the association of LCOS with 90-day mortality. A total of 186 (22%) of 849 patients in the LEVO-CTS trial developed LCOS. The factors most associated with a higher adjusted risk of LCOS were pre-operative ejection fraction [odds ratio (OR) 1.26; 95% confidence interval (CI): 1.08-1.46 per 5% decrease] and age (OR 1.13; 95% CI: 1.04-1.24 per 5-year increase), whereas isolated CABG surgery (OR 0.44, 95% CI: 0.31-0.64) and levosimendan use (OR 0.65; 95% CI: 0.46-0.92) were associated with a lower risk of LCOS. Patients with LCOS had worse outcomes, including renal replacement therapy at 30-day (10 vs. 1%) and 90-day mortality (16 vs. 3%, adjusted hazard ratio of 5.04, 95% CI: 2.66-9.55). CONCLUSION: Low cardiac output syndrome is associated with a high risk of post-operative mortality in high-risk cardiac surgery.

Prophylactic levosimendan in patients with low ejection fraction undergoing coronary artery bypass grafting: A pooled analysis of two multicentre randomised controlled trials.

OBJECTIVES: To assess the effect of preoperative levosimendan on mortality at day 90 in patients with left ventricular ejection fraction (LVEF) ≤ 40%, and to investigate a possible differential effect between patients undergoing isolated coronary artery bypass grafting (CABG) versus CABG combined with valve replacement surgery. DESIGN: Pooled analysis of two multicentre randomised controlled trials (RCT) investigating prophylactic levosimendan versus placebo prior to CABG surgery on mortality at day 90 in patients with LVEF ≤ 40%. A meta-analysis of all RCT investigating the same issue was also conducted. RESULTS: A cohort of 1084 patients (809 isolated CABG, and 275 combined surgery) resulted from the merging of LEVO-CTS and LICORN databases. Seventy-two patients were dead at day 90. The mortality at day 90 was not different between levosimendan and placebo (Hazard Ratio (HR): 0.73, 95% CI: 0.41-1.28, p = 0.27). However, there was a significant interaction between the type of surgery and the study drug (p = 0.004). We observed a decrease in mortality at day 90 in the isolated CABG subgroup (HR: 0.39, 95% CI: 0.19-0.82, p = 0.013), but not in the combined surgery subgroup (HR: 1.73, 95% CI: 0.77-3.92, p = 0.19). The meta-analysis of 6 RCT involving 1441 patients confirmed the differential effect on mortality at day 30 between the 2 subgroups. CONCLUSIONS: Preoperative levosimendan did not reduce mortality in a mixed surgical population with LV dysfunction. However, the subgroup of patients undergoing isolated CABG had a reduction in mortality at day 90, whereas there was no significant effect in combined surgery patients. This finding requires confirmation with a specific prospective trial.

Preoperative Assessment and Management of Cardiovascular Risk in Patients Undergoing Non-Cardiac Surgery: Implementing a Systematic Stepwise Approach during the COVID-19 Pandemic Era.

Major adverse cardiac events, defined as death or myocardial infarction, are common causes of perioperative mortality and major morbidity in patients undergoing non-cardiac surgery. Reduction of perioperative cardiovascular risk in relation to non-cardiac surgery requires a stepwise patient evaluation that integrates clinical risk factors, functional status and the estimated stress of the planned surgical procedure. Major guidelines on preoperative cardiovascular risk assessment recommend to establish, firstly, the risk of surgery per se (low, moderate, high) and the related timing (elective vs. urgent/emergent), evaluate the presence of unstable cardiac conditions or a recent coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), assess the functional capacity of the patient (usually expressed in metabolic equivalents), determine the value of non-invasive and/or invasive cardiovascular testing and then combine these data in estimating perioperative risk for major cardiac adverse events using validated scores (Revised Cardiac Risk Index (RCRI) or National Surgical Quality Improvement Program (NSQIP)). This stepwise approach has the potential to guide clinicians in determining which patients could benefit from cardiovascular therapy and/or coronary artery revascularization before non-cardiac surgery towards decreasing the incidence of perioperative morbidity and mortality. Finally, it should be highlighted that there is a need to implement specific strategies in the 2019 Coronavirus disease (COVID-19) pandemic to minimize the risk of transmission of COVID-19 infection during the preoperative risk assessment process.

Clinical features and outcomes in patients with cardiogenic shock complicating acute myocardial infarction: early vs recent experience with impella.

OBJECTIVES: To compare clinical features and outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) treated in the early experience with Impella percutaneous ventricular assist device and patients treated recently. BACKGROUND: Since pre-market approval (PMA) of Impella device as treatment for AMICS, use of the device has grown considerably. METHODS: We retrospectively analyzed 649 AMICS patients treated with perioperative Impella, with 291 patients treated from 2008 to 2014 comprising the early experience cohort and 358 patients treated from 2017 to 2019 comprising the recent experience cohort. The primary end point was risk adjusted in-hospital mortality. RESULTS: Mean age and gender distribution of patients was similar in the two cohorts. The recent cohort had more invasive hemodynamic monitoring (64% vs 46%; P < .001) and less use of an intra-aortic balloon pump prior to Impella (15% vs 41%; P < .001). Recently treated patients were significantly more likely to receive Impella support prior to PCI (58% vs 44%; P = .005). In-hospital mortality was lower in the recent cohort (48% vs 56%; P = .043). This difference was however no longer significant after risk adjustment (adjusted OR 0.89, 95% CI 0.59-1.34, P = .59). Rates of acute kidney injury, major bleeding, and vascular complications requiring surgery were also significantly lower in the recent cohort. CONCLUSIONS: Use of Impella for AMICS during recent years is associated with lower unadjusted in-hospital mortality, which may reflect better patient selection, earlier device implantation, and improved management algorithms. In-depth understanding of these factors may inform the development of future treatment protocols.

Association between levosimendan, postoperative AKI, and mortality in cardiac surgery: Insights from the LEVO-CTS trial.

OBJECTIVES: We aimed to evaluate the association between levosimendan treatment and acute kidney injury (AKI) as well as assess the clinical sequelae of AKI in cardiac surgery patients with depressed left ventricular function (ejection fraction <35%). METHODS: Patients in the LEVO-CTS trial undergoing on-pump coronary artery bypass grafting (CABG), valve, or CABG/valve surgery were stratified by occurrence and severity of postoperative AKI using the AKIN classification. The association between levosimendan infusion and AKI was modeled using multivariable regression. RESULTS: Among 854 LEVO-CTS patients, 231 (27.0%) experienced postoperative AKI, including 182 (21.3%) with stage 1, 35 (4.1%) with stage 2, and 14 (1.6%) with stage 3 AKI. The rate of AKI was similar between patients receiving levosimendan or placebo. The odds of 30-day mortality significantly increased by AKI stage compared to those without AKI (stage 1: adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI] 0.8-4.9; stage 2: aOR 9.1, 95% CI 3.2-25.7; stage 3: aOR 12.4, 95% CI 3.0-50.4). No association was observed between levosimendan, AKI stage, and odds of 30-day mortality (interaction P = .69). Factors independently associated with AKI included increasing age, body mass index, diabetes, and increasing baseline systolic blood pressure. Increasing baseline eGFR and aldosterone antagonist use were associated with a lower risk of AKI. CONCLUSIONS: Postoperative AKI is common among high-risk patients undergoing cardiac surgery and associated with significantly increased risk of 30-day death or dialysis. Levosimendan was not associated with the risk of AKI.

Percutaneous Coronary Intervention for Chronic Total Occlusion-The Michigan Experience: Insights From the BMC2 Registry.

OBJECTIVES: The aim of this study was to describe the performance and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in Michigan. BACKGROUND: CTO PCI has been associated with reduction in angina, but previous registry analyses showed a higher rate of major adverse cardiac events with this procedure. METHODS: To study uptake and outcomes of CTO PCI in Michigan, patients enrolled in the BMC2 (Blue Cross Blue Shield of Michigan Cardiovascular Consortium) registry (2010 to 2017) were evaluated. CTO PCI was defined as intervention in a 100% occluded coronary artery ≥3 months old. RESULTS: Among 210,172 patients enrolled in the registry, 7,389 CTO PCIs (3.5%) were attempted, with 4,614 (58.3%) achieving post-procedural TIMI (Thrombolysis In Myocardial Infarction) flow grade 3. The proportion of PCIs performed on CTOs increased over the study period (from 2.67% in 2010 to 4.48% in 2017). Thirty of 47 hospitals performed >50 CTO interventions in 2017. Pre-procedural angina class ≤2 was present in one-quarter, and functional assessment for ischemia was performed in 46.6% of patients. Major complications occurred in 245 patients (3.3%) and included death (1.4%), post-procedural stroke (0.4%), cardiac tamponade (0.5%), and urgent coronary artery bypass graft surgery (1.3%). Procedural success improved modestly from 44.5% in 2010 to 54.9% in 2017 (p for trend < 0.001). Rates of in-hospital mortality (p for trend = 0.247) and major adverse cardiac event (p for trend = 0.859) for CTO PCI remained unchanged over the study period. CONCLUSIONS: The rate of CTO PCI in Michigan increased over the study period. Although the success rate of CTO PCI has increased modestly in contemporary practice, it remained far below the >80% reported by select high-volume CTO operators. The rate of periprocedural major adverse cardiac events or death remained unchanged over time. These data suggest room for improvement in the selection and functional assessment of CTO lesions before subjecting patients to the increased procedural risk associated with CTO PCI.

Levosimendan in patients with reduced left ventricular function undergoing isolated coronary or valve surgery.

OBJECTIVE: In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures. METHODS: Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs. RESULTS: The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165). CONCLUSIONS: Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.

Comparison of nationwide trends in 30-day readmission rates after carotid artery stenting and carotid endarterectomy.

OBJECTIVE: Carotid revascularization procedures, carotid artery stenting (CAS) and carotid endarterectomy (CEA), are among the most common vascular interventions performed in the United States, with significant resource utilization. Whereas multiple studies have reported outcomes after these procedures, data regarding 30-day readmission rates after these interventions remain scant. METHODS: The U.S. Nationwide Readmission Database (2010-2014) was queried to identify all patients ≥18 years who were readmitted within 30 days after a hospital discharge for CEA or CAS. RESULTS: Among 476,260 patients included, 13.5% underwent CAS and 86.5% underwent CEA. The combined 30-day readmission rate for all carotid revascularization procedures was 9.2% (10.6% after CAS and 9.0% after CEA). After 1:3 propensity matching, CAS was associated with higher risk of readmission compared with CEA (10.4% vs 9.4%). Neurologic complications and cardiac conditions were the two most common causes of readmission after both CAS (29.7% and 23.7%, respectively) and CEA (28.2% and 21.7%, respectively). The 30-day readmission rates were higher in CAS patients across all age groups as well as in those with a low or high baseline burden of comorbidities. CONCLUSIONS: In this large nationwide study, CAS was associated with higher 30-day readmission rates compared with CEA irrespective of age or baseline burden of comorbidities. Neurologic or cardiac adverse events were responsible for >50% of readmissions after CAS and CEA.

Neutrophil-lymphocyte ratio: A prognostic tool in patients with in-hospital cardiac arrest.

BACKGROUND: In-hospital cardiac arrest (IHCA) portends a poor prognosis and survival to discharge rate. Prognostic markers such as interleukin-6, S-100 protein and high sensitivity C reactive protein have been studied as predictors of adverse outcomes after return of spontaneous circulation (ROSC); however; these variables are not routine laboratory tests and incur additional cost making them difficult to incorporate and less attractive in assessing patient's prognosis. The neutrophil-lymphocyte ratio (NLR) is a marker of adverse prognosis for many cardiovascular conditions and certain types of cancers and sepsis. We hypothesize that an elevated NLR is associated with poor outcomes including mortality at discharge in patients with IHCA. AIM: To determine the prognostic significance of NLR in patients suffering IHCA who achieve ROSC. METHODS: A retrospective study was performed on all patients who had IHCA with the advanced cardiac life support protocol administered in a large urban community United States hospital over a one-year period. Patients were divided into two groups based on their NLR value (NLR < 4.5 or NLR ≥ 4.5). This cutpoint was derived from receiving operator characteristic curve analysis (area under the curve = 0.66) and provided 73% positive predictive value, 82% sensitivity and 42% specificity for predicting in-hospital death after IHCA. The primary outcome was death or discharge at 30 d, whichever came first. RESULTS: We reviewed 153 patients with a mean age of 66.1 ± 16.3 years; 48% were female. In-hospital mortality occurred in 65%. The median NLR in survivors was 4.9 (range 0.6-46.5) compared with 8.9 (0.28-96) in non-survivors (P = 0.001). A multivariable logistic regression model demonstrated that an NLR above 4.55 [odds ratio (OR) = 5.20, confidence interval (CI): 1.5-18.3, P = 0.01], older age (OR = 1.03, CI: 1.00-1.07, P = 0.05), and elevated serum lactate level (OR = 1.20, CI: 1.03-1.40, P = 0.02) were independent predictors of death. CONCLUSION: An NLR ≥ 4.5 may be a useful marker of increased risk of death in patients with IHCA.

Meta-Analysis of Transcatheter Valve-in-Valve Implantation Versus Redo Aortic Valve Surgery for Bioprosthetic Aortic Valve Dysfunction.

Transcatheter valve-in-valve implantation (ViV-TAVI) has evolved as an alternative to redo surgical valve replacement (redo-SAVR) for high-risk patients with aortic bioprosthetic valve (BPV) dysfunction. The differences in procedural success and outcomes in a large number of patients who underwent ViV-TAVI compared with redo-SAVR for aortic BPV dysfunction are not known. We conducted a meta-analysis of the previously reported studies to determine outcomes after ViV-TAVI and redo-SAVR. PubMed, MEDLINE, and Google Scholar databases were searched for studies that reported comparative outcomes of patients who underwent either ViV-TAVI or redo-SAVR. Four observational studies met the inclusion criteria, with a total of 489 patients, 227 of whom underwent ViV-TAVI and 262 underwent redo-SAVR. Thirty-day mortality was similar in 2 groups (5% vs 4%; odds ratio [OR] = 1.08, 95% confidence interval [CI] = 0.44 to 2.62) despite the higher operative risk in the ViV-TAVI cohort as evidenced by significantly higher EuroSCORE I or II. There were similar rates of stroke (2% vs 2%; OR = 1.00, 95% CI = 0.28 to 3.59), myocardial infarction (2% vs 1%; OR = 1.08, 95% CI = 0.27 to 4.33), and acute kidney injury requiring dialysis (7% vs 10%; OR = 0.80, 95% CI = 0.36 to 0.1.77) between 2 groups but a lower rate of permanent pacemaker implantation in the ViV-TAVI group (9% vs 15%; OR = 0.44, 95% CI = 0.24 to 0.81). This meta-analysis of nonrandomized studies with modest number of patients suggested that ViV-TAVI had similar 30-day survival compared with redo-SAVR for aortic BPV dysfunction.

Association of Anemia With Outcomes in Patients Undergoing Percutaneous Peripheral Vascular Intervention: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2 VIC).

OBJECTIVES: To evaluate the clinical features and outcomes of patients with anemia undergoing percutaneous peripheral vascular intervention (PVI) in a contemporary registry. METHODS: We evaluated the differences in the clinical features and outcomes of patients with and without anemia undergoing PVI in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2 VIC) registry. Anemia was defined using World Health Organization criteria. RESULTS: Baseline anemia was present in 42.3% of 15,683 patients undergoing PVI. Compared to patients without anemia, those with anemia were older (mean age, 67 years vs 71 years), were more often black (16% vs 29%), and had higher comorbidities. Anemic patients were twice as likely to present with acute limb ischemia (5% vs 11%) and undergo urgent PVI (6% vs 15%) or below-the-knee PVI (18% vs 35%). Many in-hospital adverse events were higher in anemic patients. In a propensity-matched cohort, any adverse outcome (3.4% vs 8.4%; odds ratio [OR], 2.58; 95% confidence interval [CI], 1.94-3.42) or major cardiovascular event, defined as death, myocardial infarction, stroke, or amputation (1.1% vs 3.2%; OR, 2.96; 95% CI, 1.83-4.79) was more likely in anemic patients. Of all adverse events, the highest odds were observed for post-PVI transfusions and amputations in anemic patients. Multivariable logistic regression showed that baseline hemoglobin (1 g/dL below the normal value) was associated with greater risk of any adverse event (OR, 1.57; 95% CI, 1.47-1.68). CONCLUSION: The prevalence of anemia was high among PVI patients and was associated with significantly greater likelihood of amputation, any adverse event, and major cardiovascular events. Whether preprocedure correction of anemia has the potential to decrease post-PVI adverse events remains to be studied.

Incidence and outcomes of emergent cardiac surgery during transfemoral transcatheter aortic valve implantation (TAVI): insights from the European Registry on Emergent Cardiac Surgery during TAVI (EuRECS-TAVI).

Aims: Life-threatening complications occur during transcatheter aortic valve implantation (TAVI) which can require emergent cardiac surgery (ECS). Risks and outcomes of patients needing ECS during or immediately after TAVI are still unclear. Methods and results: Incidence, risk factors, management, and outcomes of patients requiring ECS during transfemoral (TF)-TAVI were analysed from a contemporary real-world multicentre registry. Between 2013 and 2016, 27 760 patients underwent TF-TAVI in 79 centres. Of these, 212 (0.76%) patients required ECS (age 82.4 ± 6.3 years, 67.5% females, logistic EuroSCORE: 17.1%, STS-score 5.8%). The risk of ECS declined from 2013 (1.07%) to 2014 (0.70%) but remained stable since. Annual TF-TAVI numbers have more than doubled from 2013 to 2016. Leading causes for ECS were left ventricular perforation by the guidewire (28.3%) and annular rupture (21.2%). Immediate procedural mortality (<72 h) of TF-TAVI patients requiring ECS was 34.6%. Overall in-hospital mortality was 46.0%, and highest in case of annular rupture (62%). Independent predictors of in-hospital mortality following ECS were age > 85 years [odds ratio (OR) 1.87, 95% confidence interval (95% CI) (1.02-3.45), P = 0.044], annular rupture [OR 1.96, 95% CI (0.94-4.10), P = 0.060], and immediate ECS [OR 3.12, 95% CI (1.07-9.11), P = 0.037]. One year of survival of the 114 patients surviving the in-hospital period was only 40.4%. Conclusion: Between 2014 and 2016, the need for ECS remained stable around 0.7%. Left ventricular guidewire perforation and annular rupture were the most frequent causes, accounting for almost half of ECS cases. Half of the patients could be salvaged by ECS-nevertheless, 1 year of all-cause mortality was high even in those ECS patients surviving the in-hospital period.

Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery.

BACKGROUND: Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery. METHODS: In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 µg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 µg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5. RESULTS: A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups. CONCLUSIONS: Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. (Funded by Tenax Therapeutics; LEVO-CTS ClinicalTrials.gov number, NCT02025621 .).

Nonsteroidal Anti-Inflammatory Drugs and Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Surgery.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in perioperative pain management of patients undergoing coronary artery bypass graft surgery. However, the association of periprocedural use of NSAIDs and clinical outcomes after coronary artery bypass graft is understudied. METHODS: We conducted a retrospective analysis using pooled data from 2 multicenter randomized controlled trials (PREVENT IV [n = 3014] and MEND-CABG II [n = 3023]). Rates of death, death or myocardial infarction, and death, myocardial infarction, or stroke in the 30 days following coronary artery bypass graft surgery were compared in patients using or not using perioperative NSAIDs. Inverse probability of treatment weighting and Cox proportional hazards regression models were used to adjust for confounding. RESULTS: A total of 5887 patients were studied. Median age was 65 years, 78% were male, and 91% were White. NSAIDs were used in 2368 (40.2%) patients. The majority of patients (1822 [30.9%]) received NSAIDs after coronary artery bypass graft surgery; 289 (4.9%) used them prior to and after the surgery; and 257 (4.4) received NSAIDs prior to the surgery only. Adjusted 30-day outcomes were similar in patients receiving and not receiving NSAIDs (death: hazard ratio [HR] 1.18; 95% confidence interval [CI], 0.48-2.92; death or myocardial infarction: HR 0.87; 95% CI, 0.42-1.79; death, myocardial infarction, or stroke: HR 0.87; 95% CI, 0.46-1.65). CONCLUSION: In this pooled data analysis, perioperative NSAID use was common among patients undergoing coronary artery bypass graft surgery and was not associated with an increased short-term risk for major adverse clinical outcomes.

Levosimendan in patients with left ventricular systolic dysfunction undergoing cardiac surgery on cardiopulmonary bypass: Rationale and study design of the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial.

BACKGROUND: Low cardiac output syndrome is associated with increased mortality and occurs in 3% to 14% of patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). Levosimendan, a novel calcium sensitizer and KATP channel activator with inotropic, vasodilatory, and cardioprotective properties, has shown significant promise in reducing the incidence of low cardiac output syndrome and related adverse outcomes in patients undergoing cardiac surgery on CPB. METHODS: LEVO-CTS is a phase 3 randomized, controlled, multicenter study evaluating the efficacy, safety, and cost-effectiveness of levosimendan in reducing morbidity and mortality in high-risk patients with reduced left ventricular ejection fraction (≤35%) undergoing cardiac surgery on CPB. Patients will be randomly assigned to receive either intravenous levosimendan (0.2 µg kg-1 min-1 for the first hour followed by 0.1 µg/kg for 23hours) or matching placebo initiated within 8hours of surgery. The co-primary end points are (1) the composite of death or renal replacement therapy through day 30 or perioperative myocardial infarction, or mechanical assist device use through day 5 (quad end point tested at α<.01), and (2) the composite of death through postoperative day 30 or mechanical assist device use through day 5 (dual end point tested at α<.04). Safety end points include new atrial fibrillation and death through 90days. In addition, an economic analysis will address the cost-effectiveness of levosimendan compared with placebo in high-risk patients undergoing cardiac surgery on CPB. Approximately 880 patients will be enrolled at approximately 60 sites in the United States and Canada between July 2014 and September 2016, with results anticipated in January 2017. CONCLUSION: LEVO-CTS, a large randomized multicenter clinical trial, will evaluate the efficacy, safety, and cost-effectiveness of levosimendan in reducing adverse outcomes in high-risk patients undergoing cardiac surgery on CPB. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02025621).

Clopidogrel use After Myocardial Revascularization: Prevalence, Predictors, and One-Year Survival Rate.

INTRODUCTION: Antiplatelet therapy after coronary artery bypass graft (CABG) has been used. Little is known about the predictors and efficacy of clopidogrel in this scenario. OBJECTIVE: Identify predictors of clopidogrel following CABG. METHODS: We evaluated 5404 patients who underwent CABG between 2000 and 2009 at Duke University Medical Center. We excluded patients undergoing concomitant valve surgery, those who had postoperative bleeding or death before discharge. Postoperative clopidogrel was left to the discretion of the attending physician. Adjusted risk for 1-year mortality was compared between patients receiving and not receiving clopidogrel during hospitalization after undergoing CABG. RESULTS: At hospital discharge, 931 (17.2%) patients were receiving clopidogrel. Comparing patients not receiving clopidogrel at discharge, users had more comorbidities, including hyperlipidemia, hypertension, heart failure, peripheral arterial disease and cerebrovascular disease. Patients who received aspirin during hospitalization were less likely to receive clopidogrel at discharge (P≤0.0001). Clopidogrel was associated with similar 1-year mortality compared with those who did not use clopidogrel (4.4% vs. 4.5%, P=0.72). There was, however, an interaction between the use of cardiopulmonary bypass and clopidogrel, with lower 1-year mortality in patients undergoing off-pump CABG who received clopidogrel, but not those undergoing conventional CABG (2.6% vs 5.6%, P Interaction = 0.032). CONCLUSION: Clopidogrel was used in nearly one-fifth of patients after CABG. Its use was not associated with lower mortality after 1 year in general, but lower mortality rate in those undergoing off-pump CABG. Randomized clinical trials are needed to determine the benefit of routine use of clopidogrel in CABG.

Relation of Baseline Renal Dysfunction With Outcomes in Patients Undergoing Popliteal and Infrapopliteal Percutaneous Peripheral Arterial Interventions.

Renal dysfunction is a major risk factor for peripheral arterial disease (PAD). Infrapopliteal PAD is associated with more co-morbid conditions and worse prognosis than suprapopliteal PAD. Long-term outcomes of patients with renal dysfunction and popliteal or infrapopliteal PAD undergoing peripheral vascular intervention (PVI) are not well described. We retrospectively evaluated long-term outcomes in 726 patients undergoing infrapopliteal PVI categorized into 3 glomerular filtration rate (GFR)-based groups: GFR (≥60 ml/min/1.73 m(2)), GFR (<60 ml/min/1.73 m(2)), and those on dialysis. At mean follow-up of 36 ± 20 months, amputation rates were 3%, 5%, and 11% with mortality rates of 23%, 36%, and 56% in normal renal function, chronic kidney disease (adjusted odds ratio [OR] for amputation 1.75, 95% CI 0.73 to 4.21; adjusted OR for mortality 1.53, 95% CI 1.05 to 2.23, p = 0.028), and dialysis (adjusted OR for amputation 2.43, 95% CI 0.84 to 7.02, p = 0.100; adjusted OR for mortality 4.51, 95% CI 2.46 to 8.26, p <0.0001) groups, respectively. Repeat revascularization was similar in all 3 groups at roughly 25%. In conclusion, chronic kidney disease and dialysis were associated with increased major amputations and mortality in patients who received PVI for popliteal and infrapopliteal PAD.

Outcomes of transfemoral transcatheter aortic valve implantation at hospitals with and without on-site cardiac surgery department: insights from the prospective German aortic valve replacement quality assurance registry (AQUA) in 17 919 patients.

AIMS: Performing transcatheter aortic valve implantation (TAVI) at hospitals with only cardiology department but no cardiac surgery (CS) on-site is at great odds with current Guidelines. METHODS AND RESULTS: We analysed data from the official, prospective German Quality Assurance Registry on Aortic Valve Replacement to compare characteristics and in-hospital outcomes of patients undergoing transfemoral TAVI at hospitals with (n = 75) and without CS departments (n = 22). An interdisciplinary Heart Team was established at all centres (internal staff physicians at hospitals with on-site CS; in-house cardiologists and visiting cardiac surgical teams from collaborating hospitals at non-CS hospitals). In 2013 and 2014, 17 919 patients (81.2 ± 6.1 years, 55% females, German aortic valve (GAV) score 2.0 5.6 ± 5.8%, logistic EuroSCORE I 21.1 ± 15.4%) underwent transfemoral TAVI in Germany: 1332 (7.4%) at hospitals without on-site CS department. Patients in non-CS hospitals were older (82.1 ± 5.8 vs. 81.1 ± 6.1 years, P < 0.001), with more frequent co-morbidities. Predicted mortality risks per GAV-score 2.0 (6.1 + 5.5 vs. 5.5 ± 5.9%, P < 0.001) and logEuroSCORE I (23.2 ± 15.8 vs. 21.0 ± 15.4%, P < 0.001) were higher in patients at non-CS sites. Complications, including strokes (2.6 vs. 2.3%, P = 0.452) and in-hospital mortality (3.8 vs. 4.2%, P = 0.396), were similar in both groups. Matched-pair analysis of 555 patients in each group with identical GAV-score confirmed similar rates of intraprocedural complications (9.2 vs. 10.3%, P = 0.543), strokes (3.2% for both groups, P = 1.00), and in-hospital mortality (1.8 vs. 2.9%, P = 0.234). CONCLUSION: Although patients undergoing TAVI at hospitals without on-site CS department were older and at higher predicted perioperative death risk, major complications, and in-hospital mortality were not statistically different, suggesting the feasibility and safety of Heart Team-based TAVI at non-CS sites. These findings need confirmation in future randomized study.