Clues of incomplete reversal of heparin in cardiac surgery.

OBJECTIVES: In our center, an unusual rate of patients had abnormalities of hemostasis in immediate postoperative period of cardiac surgery. Our objectives were to identify the cause of these sudden hemostasis abnormalities and to evaluate the performances of point of care coagulation testing. METHODS: In this prospective and descriptive study, we included 33 consecutive patients undergoing elective cardiac surgery for 1 month. Heparin-induced anticoagulation and calculation of the protamine dose were tested by the Hemostasis Management System Plus device (Medtronic, Minneapolis, MN, USA). Fifteen minutes after the end of the protamine infusion, activated clotting time (ACT), activated partial thromboplastin time and anti Xa activity were measured. In case of unusual clinical bleeding, a Quantra analysis (Stago, HemoSonics LLC, Charlottesville, VA) was added. RESULTS: Residual antiXa activity >0.2 IU/mL after neutralization was present in 44% of patients. Our investigation concluded incomplete heparin reversal. There was no association between cellular reinfusate and the presence of heparin. The unusual rate of hemostasis abnormalities was explained by a less efficient protamine reversal of heparin. ACT and Clot Time Ratio (CTR, Quantra system) correlated with AntiXa with Spearman's coefficients of 0.85 (p < .0001) and 0.95 (p = .0012), respectively. About ACT, a threshold of 150 seconds had a sensitivity of 85% [58-97] and a specificity of 85% [58-97%] for detection of AntiXa>0.2. For CTR, a threshold of 1.4 had a sensitivity of 67% [30-94] and a specificity of 100% [18-100]. CONCLUSION: The use of point of care coagulation testing is effective in detecting incomplete reversal of heparin.

A Massive Venlafaxine Intoxication: Evolution of Cardiac Toxicity with Venlafaxine and O-Desmethylvenlafaxine Elimination Kinetics: A Grand Round.

BACKGROUND: This study presents the case of a 19-year-old woman who attempted suicide by ingesting 11.25 g of venlafaxine (V). She was admitted to the hospital with severe biventricular dysfunction, progressing to cardiac arrest requiring extracorporeal circulatory life support for 11 days. The pharmacokinetics of venlafaxine during impaired cardiac output and the effect of its active metabolite, the O-desmethylvenlafaxine (ODV), are currently not very well understood. METHODS AND RESULTS: Serum concentrations of V and ODV were monitored twice daily for 3 weeks. The maximum concentrations of venlafaxine and ODV were at 14 hours after ingestion, with 29,180 mcg/L for V and 5399 mcg/L for ODV. Half-lives increased, requiring 2 weeks to eliminate the drug. The left ventricular ejection fraction significantly improved when V + ODV was below 1000 mcg/L and remained altered until the ODV concentrations were lower than 400 mcg/L. CONCLUSIONS: This report, with complete elimination kinetic of V and ODV in a monodrug intoxication, provides information about the modification of pharmacokinetics in the case of an overdose managed by extracorporeal circulatory life support, the cardiac toxicity of ODV, and the value of the toxic threshold for the active moiety.

Which echocardiographic parameters improve the risk prediction for peri-operative outcomes in patients undergoing coronary bypass surgery: a prospective study.

OBJECTIVE: To assess the performance of transthoracic echocardiographic parameters to predict operative mortality and morbidity in patients undergoing coronary artery bypass grafting, and to assess its incremental prognostic value as compared to the Society of Thoracic Surgeons (STS) score. MATERIALS AND METHODS: We prospectively collected the clinical and biological data required to calculate the STS score in patients hospitalised for coronary artery bypass grafting. Preoperative transthoracic echocardiography was performed for each patient. The primary endpoint was 30-day mortality or major morbidity (i.e. stroke, renal failure, prolonged ventilation, deep sternal wound infection, reoperation) as defined by the STS. The secondary endpoint was prolonged hospitalisation for over 14 days. RESULTS: A total of 172 patients was included (mean age 66.1±10.2 years, 12.2% were women). The primary endpoint occurred in 33 patients (19.2%), and 28 patients (16.3%) had a prolonged hospital stay. Independent predictive factors for the primary endpoint were an increased left atrial volume (>31 mL/m²; odds ratio (OR) 3.55, 95% confidence interval (CI) 1.38-9.12; P=0.004) and a decreased tricuspid annular plane systolic excursion (<20 mm; OR 3.45, 95% CI 1.47-8.21; P=0.008). The predictive value of the multivariate model increased when the two echocardiographic parameters were added to the STS score (area under the curve 0.598 vs. 0.695, P=0.001; integrated discrimination improvement 7.44%). CONCLUSION: In patients undergoing coronary artery bypass grafting, preoperative assessment of left atrial size and tricuspid annular plane systolic excursion should be performed systematically, as it provides additional prognostic information to the STS score.

Immature Granulocytes: A Risk Factor of Infection after Cardiac Surgery.

BACKGROUND: Similarly, to sepsis, cardiac surgery with cardiopulmonary bypass (CPB) induces major changes in leukocyte subsets. Immature granulocytes (IGs) increase both in sepsis and after open-heart surgery. Secondary infections are a major complication of cardiac surgery with CPB. We hypothesized that the assessment of leukocyte subsets with multicolor flow cytometry (FCM) could help the front-line clinician to better identify patients at high risk of infectious complications in this clinical setting. METHODS: In this single-center observational pilot study, we identified 26 leukocyte subsets using three combinations of antibodies (from 5 to 10 colors per combinations): one devoted to granulocytes, one to lymphocyte subpopulations and one for rare cells (plasma cells and dendritic cells). Blood samples were obtained preoperatively and immediately after open-heart surgery under CPB in 59 patients without immuno-depression, chronic or neoplastic inflammatory disease, and immunosuppressive treatment. Secondary infections during hospital stay were recorded. RESULTS: Patients exhibited postoperative NK and T-cell lymphopenia, increased levels of IGs and monocytes with low levels of surface HLA DR. Twelve patients developed secondary infectious complications. Only immediate postoperative IG levels were significantly higher in these patient (6.6 [6; 7.39] G/L vs. 3.8 [2.67; 5.72] G/L, P = 0.01). Patients with immediate postoperative increase of IGs developed more frequently infectious complication (10/22 [46%] vs. 2/37 [5%]: P < 0.001). CONCLUSIONS: This study suggests that postoperative increase of IGs is related to postoperative organ failure and promises to help in early identification of patients at risk of infectious complications after open-heart surgery under CPB. © 2018 International Clinical Cytometry Society.

Relation Between Renin-Angiotensin System Blockers and Survival Following Isolated Aortic Valve Replacement for Aortic Stenosis.

Renin-angiotensin system blockers (RASb) improve cardiac remodeling, but their clinical utility after surgical aortic valve replacement (SAVR) for aortic stenosis (AS) is unclear. We aimed to assess the impact of RASb on short- and long-term survival following isolated SAVR for severe AS. From January 2005 to January 2014, 508 consecutive patients had isolated SAVR for severe AS. Patients with RASb (n = 286; 53%) were more often female (p = 0.039), hypertensive (p < 0.0001), and diabetic (p = 0.004), with higher body mass index (p < 0.0001) and EuroSCORE II (p = 0.025), and lower mean aortic pressure gradient (p = 0.011). The 30-day mortality was similar in both groups (RASb: 3% vs no RASb: 5.8%, p = 0.13), but lower under angiotensin receptor blockers (ARB) than angiotensin-converting enzyme inhibitors (ACEi; 0.7% vs 5.6%, p = 0.017). Patients under RASb had a better 8-year survival than those without RASb (83 ± 3% vs 52 ± 5%, p < 0.0001), confirmed in a propensity score-matched pairs analysis (82 ± 4% vs 50 ± 7%, p < 0.0001). Regarding different types of RASb, patients under ARB had lower mortality than those under ACEi (87 ± 3% vs 79 ± 4%, p = 0.028). In multivariate analysis, the use of RASb was associated with improved survival (hazard ratio = 0.31, 95% confidence interval 0.20 to 0.47, p < 0.0001), with lower mortality under ARB than under ACEi (hazard ratio = 0.39, 95% confidence interval 0.18 to 0.85, p = 0.018). In this observational study, the use of RASb was associated with improved long-term outcome after isolated SAVR for severe AS. A randomized clinical trial is mandatory.

Usefulness of Electrocardiographic Strain to Predict Survival After Surgical Aortic Valve Replacement for Aortic Stenosis.

Electrocardiographic (ECG) strain has been reported as a specific marker of midwall left ventricular (LV) myocardial fibrosis, predictive of adverse clinical outcomes in aortic stenosis (AS), but its prognostic impact after aortic valve replacement (AVR) is unknown. We aimed to assess the impact of ECG strain on long-term mortality after surgical AVR for AS. From January 2005 to January 2014, patients with interpretable preoperative ECG who underwent isolated AVR for AS were included. ECG strain was defined as ≥1-mm concave downslopping ST-segment depression with asymmetrical T-wave inversion in lateral leads. Mortality was assessed over a follow-up period of 4.8 ± 2.7 years. Among the 390 patients included, 110 had ECG strain (28%). They had significantly lower body mass index, higher mean transaortic pressure gradient and Cornell-product ECG LV hypertrophy than in those without ECG strain. There was also a trend for lower LV ejection fraction in patients with ECG strain as compared with those without. Patients with ECG strain had significantly lower 8-year survival than those without. ECG strain remained associated with reduced survival both in patients with and without LV hypertrophy (p <0.0001 for both). After adjustment, ECG strain remained a strong and independent determinant of long-term survival (hazard ratio 4.4, p <0.0001). Similar results were found in patients with LV hypertrophy or without LV hypertrophy. In the multivariate model, the addition of ECG strain provided incremental prognostic value (p <0.0001). In conclusion, in patients with AS, ECG strain is associated with 4-fold increased risk of long-term mortality after isolated AVR, regardless of preoperative LV hypertrophy.