Ivan Philip

G894T Polymorphism in the Endothelial Nitric Oxide Synthase Gene Is Associated With an Enhanced Vascular Responsiveness to Phenylephrine

BACKGROUND Differences in vascular reactivity to phenylephrine (PE) responsiveness have been largely evidenced in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Because nitric oxide (NO) strongly affects modulation of the vascular tone in response to vasopressor agents, we hypothesized that the G894T polymorphism of the endothelial NO synthase gene (eNOS) could be related to changes in the pressor response to PE. METHODS AND RESULTS The protocol was performed in 68 patients undergoing coronary artery bypass grafting (n=33) or valve surgery (n=35) in whom mean arterial pressure decreased below 65 mm Hg during normothermic CPB. Under constant and nonpulsatile pump flow conditions (2 to 2.4 L. min-1. m-2), a PE dose-response curve was generated by the cumulative injection of individual doses of PE (25 to 500 micrograms). The G894T polymorphism of the eNOS gene was determined, and 3 groups were defined according to genotype (TT, GT, and GG). Groups were similar with regard to perioperative characteristics. The PE dose-dependent response was significantly higher in the allele 894T carriers (TT and GT) than in the homozygote GG group (P=0.02), independently of possible confounding variables. CONCLUSIONS These results evidenced an enhanced responsiveness to alpha-adrenergic stimulation in patients with the 894T allele in the eNOS gene.

Cardiac troponin I is an independent predictor of in-hospital death after adult cardiac surgery.

Background Although myocardial injury during cardiac surgery is associated with impaired clinical outcome, little is known about the prognostic value of cardiac troponin I (cTnI), a cardiac-specific biologic marker. The purpose of this prospective study was to evaluate the prognostic value of cTnI concentrations measured 20 h after the end of surgery in adult patients undergoing coronary artery bypass grafting or conventional valve surgery. Methods Baseline and perioperative characteristics of 502 consecutive patients undergoing conventional heart surgery during a 1-yr period were collected. In-hospital death (n = 28) and major clinical outcomes, e.g., low cardiac output, ventricular arrhythmia, and renal failure, were recorded. Results Multivariate analysis, using a stepwise logistic regression, showed that cTnI concentration was an independent predictor of in-hospital mortality (for cTnI concentration > 13 ng/ml, odds ratio = 6.7 [95% confidence interval, 2.3–19.3]), as were diabetes, altered preoperative cardiac function, emergent surgery, cardiopulmonary bypass duration, postoperative Pao2 level and total chest drainage volume. Further, elevated cTnI concentrations were associated with a cardiac cause of death and with major clinical outcomes. Conclusions Our results demonstrated that cTnI concentration measured 20 h after the end of surgery is an independent predictor of in-hospital death after cardiac surgery. In addition, elevated concentrations of cTnI are associated with a cardiac cause of death and with major postoperative complications.

Cardiac troponin I in diagnosis of perioperative myocardial infarction after cardiac surgery

OBJECTIVE The diagnosis of perioperative myocardial infarction (PMI) after cardiac surgery remains an important issue. The present study was designed to determine the relevance of the measurement of serum cardiac troponin I (cTnI, a biochemical marker with high cardiospecificity. Therefore, cTnI was compared with creatine kinase-MB (CK-MB) mass and to the other classical signs of myocardial infarction after cardiac surgery. DESIGN A prospective study. SETTING A university hospital. PARTICIPANTS Forty-one patients undergoing coronary artery bypass grafting (CABG) (n = 17) or valvular replacement (n = 24). These patients were separated into three groups according to postoperative complications: group 1, Q-wave PMI (n = 5); group 2, nonspecific changes (non-Q wave) on the electrocardiogram (ECG) and/or need of inotropic support (n = 12); group 3, no postoperative complication (n = 24). INTERVENTIONS Postoperative follow-up consisted of serial determination of different biochemical markers (CK, CK-MB, cTnI), ECGs, and echocardiography. Blood samples were drawn before (H0) and 3 (H3), 12 (H12), 20 (H20), 24 (H24), and 48 (H48) hours after the onset of cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS In all patients in group 3, CK-MB and cTnI concentrations increased, and peaked at H12 after CPB (13.4 +/- 7.7 and 7.1 +/- 4.1 micrograms/L for CK-MB and cTnI, respectively). In group 1, cTnI concentrations were significantly higher than in group 3 from H12 until H48 (p < 0.002), peaked later (H24; 59.0 +/- 38.8 micrograms/L), and remained in plateau. In group 2, cTnI peak concentrations were significantly different than in groups 1 and 3 (26.2 +/- 14.8 micrograms/L) and occurred at H24 (as in patients with Q-wave PMI). CONCLUSION A cTnI concentration less than 15 micrograms/L (mean + 2 standard deviations [SDs] of peak cTnI in group 3) within 24 to 48 hours after cardiac surgery is highly suggestive of the absence of perioperative myocardial necrosis. Because of its higher cardiospecificity than CK-MB mass, and its prolonged release after myocardial necrosis, cTnI might be a useful tool in the diagnosis of PMI after cardiac surgery.

Plasma brain natriuretic peptide and cardiac troponin I concentrations after adult cardiac surgery: association with postoperative cardiac dysfunction and 1-year mortality.

Objective:The purpose of the present study was to evaluate the prognostic implications of perioperative B-type natriuretic peptide (BNP) and cardiac troponin I concentrations in patients undergoing cardiopulmonary bypass for cardiac surgery. Design:Prospective observational study. Setting:Biochemistry laboratory and surgical care unit in a university hospital. Patients:A total of 92 consecutive patients undergoing elective coronary artery (43 patients) or valve surgery (49 patients). Interventions:None. Measurements and Main Results:BNP and cardiac troponin I concentrations were measured before surgery (day 0), and at day 1 after surgery. Postoperative cardiac dysfunction was defined as low cardiac output or hemodynamic instability requiring inotropic support for >24 hrs or congestive heart failure until day 5. One-year survival was also evaluated. Univariate and multivariate analyses were performed. An important BNP secretion was systematically observed after cardiac surgery. Independent predictors of cardiac dysfunction were preoperative New York Health Association class and BNP and cardiac troponin I concentrations measured at day 1. Patients with an elevation of both markers have a 12-fold increased risk of postoperative heart failure. The use of both markers in combination predicted better postoperative heart failure than each one separately. Age, low preoperative left ventricular ejection fraction, and elevated BNP at day 1 (>352 pg/mL) were associated with an increased mortality rate at 1 yr. In multivariate analysis, only left ventricular ejection fraction was significantly associated with 1-yr survival. Conclusions:Postoperative plasma BNP and cardiac troponin I levels are independent predictors of postoperative cardiac dysfunction after cardiac surgery. Simultaneous measurement of BNP and cardiac troponin I improve the risk assessment of postoperative cardiac dysfunction. However, the association between BNP levels and 1-yr outcome was no longer significant after adjustment on left ventricular ejection fraction.

Anesthesia and Perioperative Management of Patients Undergoing Transcatheter Aortic Valve Implantation: Analysis of 90 Consecutive Patients With Focus on Perioperative Complications

OBJECTIVE To describe, from the point of view of anesthesia and intensive care specialists, the perioperative management of high-risk patients with aortic stenosis who underwent transcatheter (transfemoral and transapical) aortic valve implantation (TAVI). The authors specifically focused on immediate postoperative complications. DESIGN Retrospective review of collected data. SETTING Academic hospital. PARTICIPANTS Ninety consecutive patients with severe aortic stenosis who underwent TAVI. INTERVENTIONS General anesthesia followed by postoperative care. Complications were defined by pre-established criteria. MEASUREMENTS AND MAIN RESULTS Of 184 patients referred between October 2006 and February 2009, 90 were consecutively treated with TAVI because of a high surgical risk or contraindications to surgery. The transfemoral approach was used as the first option (n = 62), and the transapical approach when contraindications to the former were present (n = 28). Results are presented as mean ± standard deviation or median (25-75 percentiles) as appropriate. Patients were 81 ± 8 years old, in New York Heart Association classes II (9%), III (54 %), or IV (37%); left ventricular ejection fraction was below 0.5 in 38% of patients. The predicted surgical mortality was 24% (16-32) and 15% (11-23) with the logistic EuroSCORE and STS-Predicted Risk of Mortality, respectively. The valve was implanted in 92% of the cases. The duration of anesthesia and (intra- and postoperative) mechanical ventilation was 190 (160-230) minutes and 245 (180-420) minutes, respectively. Hospital mortality was 11%. The most frequent cardiac complications were heart failure (20%) and atrioventricular block (16%), with 6% requiring a pacemaker. Vascular complications (major and minor) occurred in 29% of the patients. CONCLUSIONS Despite their severe comorbidities, the mortality of the patients in this cohort was below that predicted by cardiac surgery risk scores. Monitoring, hemodynamic instability, and the frequency of complications require management and follow-up of these patients in similar ways as for open cardiac surgery. The frequency of complications in this cohort was comparable to that published by other groups.

Angiotensin II Type 1 Receptor Gene Polymorphism Is Associated with an Increased Vascular Reactivity in the Human Mammary Artery in vitro

A gene polymorphism of the angiotensin II (AII) type 1 receptor has been described previously (A to C transversion at position 1166). Besides the epidemiological studies needed to determine a possible relationship between the polymorphism and some cardiovascular diseases, no study has been conducted to determine the impact of the polymorphism on vascular functions. At subthreshold concentrations, within the physiological range, AII potentiates α-adrenergic-dependent vascular tone. We investigated phenylephrine-induced tone and its amplification by AII (10 pmol/l) in human internal mammary artery rings mounted in organ baths. We performed concentration-response curves to phenylephrine (0.1–100 µmol/l) before and after pretreatment with AII (10 pmol/l). Patients had the genotype AA (n = 20) or the A to C transversion (AC/CC, n = 30). Contractions to phenylephrine (0.1–100 µmol/l) were significantly higher in rings from AC/CC than from AA patients (maximum response: 1.47±0.07 vs. 1.22±0.06 mN/mg, p < 0.001). AII (10 pmol/l) induced a significant potentiation of phenylephrine-induced contraction (e.g. 58.9% increase in tone with 1 µmol/l phenylephrine, p < 0.001) which was significantly lower in the AC/CC than in the AA group (46±9 vs. 66±7% with 1 µmol/l phenylephrine, p < 0.01). Contractions to AII (1 or 100 nmol/l) were not significantly affected by the genotype. Although the study was performed in arteries from patients with a coronary artery disease, these changes in vascular reactivity might be of interest in the understanding of the relationship between a possible higher probability of cardiovascular disorder and the genetic polymorphism of the AII type 1 receptor.

Comparison of minithoracotomy and conventional sternotomy approaches for valve surgery

OBJECTIVE To compare patients undergoing valve surgery through a minithoracotomy approach with a matched group undergoing conventional valve surgery. DESIGN Control study. SETTING University hospital, single center. PARTICIPANTS Forty-one consecutive patients scheduled for valve surgery by minithoracotomy approach were matched with a similar group of patients operated on by the sternotomy approach. INTERVENTIONS Criteria for matching included type of valve procedure (aortic valve replacement or mitral valve repair), age, surgeons, and left ventricular function. Two surgeons performed the surgical procedures. Perioperative care was standardized for all patients. Operative and postoperative data were recorded. MEASUREMENTS AND MAIN RESULTS The 41 pairs of patients were correctly matched, except for left ventricular function (n = 1). Twenty patients underwent mitral valve repair and 62 aortic valve replacement. Preoperative demographic data and clinical characteristics were similar in both groups. Cardiopulmonary bypass, aortic clamping, and surgery times were longer in the minithoracotomy group (p < 0.05). In 3 patients, the minithoracotomy approach had to be converted into a sternotomy during the surgical procedure for better visualization. Minithoracotomy patients had significantly increased postoperative total blood loss (p < 0.05). No difference was found between the groups for extubation time and intensive care or in-hospital lengths of stay. CONCLUSION These results suggest that valve surgery is feasible in many cases through minithoracotomy. Nevertheless, this approach increases surgical complexity and in this comparative study no significant benefit was shown.

Hyperprocalcitonemia in patients with perioperative myocardial infarction after cardiac surgery.

ObjectiveTo describe and compare procalcitonin (PCT) concentrations after cardiac surgery in uncomplicated patients and in patients with perioperative myocardial infarction (PMI). DesignRetrospective comparative study. SettingOne university hospital. PatientsFifty-eight adult patients undergoing cardiac surgery. InterventionNone. Measurements and Main Results In a first step, plasma PCT and C-reactive protein concentrations were measured preoperatively and until 72 hrs postoperatively in ten consecutive patients who underwent uncomplicated cardiac surgery. PCT concentrations increased progressively from the end of cardiopulmonary bypass (0.09 ± 0.09 ng/mL), peaked at 24 hrs postoperatively (1.14 ± 1.24 ng/mL), and began to decrease at 48 hrs. C-reactive protein appeared to peak at 48 hrs (from 5.8 ± 11.7 mg/L preoperatively to 265.1 ± 103.5 mg/L on the second postoperative day). In a second step, PCT concentrations were measured at day one in 23 patients (PMI group) who presented high postoperative plasma cardiac troponin I concentrations and were compared with PCT concentrations observed in 25 matched uncomplicated patients. All patients were free from infection. PCT in the PMI group was significantly higher than in the control group (27.1 ± 63.2 vs. 2.0 ± 2.4 ng/mL, respectively;p = .0053). ConclusionBecause high plasma concentrations of PCT were found in patients with PMI after cardiac surgery, it may be suggested that, in the early postoperative period, elevated plasma PCT concentrations should be interpreted with caution regarding infection diagnosis.

Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide-stimulated whole blood cells: roles of interleukin-10 and the extracorporeal circuit.

Objective To determine whether cardiopulmonary bypass (CPB) alters the ex vivo cytokine production of whole blood cells stimulated by lipopolysaccharide (LPS) and to assess the roles of interleukin (IL)-10 and an extracorporeal circuit (ECC) in the alteration. Design Prospective, controlled study. Setting Biochemistry laboratory and surgical intensive care unit in a university hospital. Patients Seventeen consecutive adult patients undergoing coronary artery bypass grafting or valve surgery with normothermic CPB and eight healthy volunteers. Interventions Blood samples for cytokine measurement were drawn from patients before and during (at 60, 90, 120, 180 and 360 mins) CPB and were cultured with and without LPS and with and without anti-IL-10 antibodies. Blood was also drawn from healthy subjects and sampled for cytokine analysis before and during circulation in an isolated ECC. Measurements and Main Results The concentrations of ex vivo tumor necrosis factor (TNF)-&agr;, IL-6, IL-8, and IL-10, measured by enzyme-linked immunosorbent assay, were reduced in both experimental settings. In patients on CPB, LPS hyporesponsiveness was detected at 60 mins after the onset of CPB and was maximal at 120 mins (78% to 86% decreases from pre-CPB levels) but was transient, except for TNF-&agr;. The plasma concentration of IL-10 peaked at 90 mins after the start of CPB, but the role of IL-10 in LPS hyporesponsiveness appears limited because anti-IL-10 antibodies significantly increased ex vivo production of IL-6 but not TNF-&agr; or IL-8. In the isolated ECC study, no IL-10 was detected in plasma, yet the ex vivo production of the cytokines (except IL-8) was decreased (by 66% to 95%). Conclusion Our results demonstrate the following: a) CPB induces an early and transient LPS hyporesponsiveness of whole blood as measured by cytokine production; b) IL-10 seems only partly involved in this process, and its role is restricted to an in vivo situation; and c) contact of blood with an ECC is sufficient to induce LPS hyporesponsiveness.

The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation: An in-vitro study.

BACKGROUND Management of ticagrelor-induced bleeding is challenging, as no antidote is currently available. Platelet transfusion, usually proposed to reverse antiplatelet drugs, has been suggested to be ineffective but few data are available. OBJECTIVE To assess the efficacy of platelet supplementation to restore platelet aggregation inhibited by ticagrelor. DESIGN In vitro study. SETTING Blood samples were obtained from the French Blood Bank Institute. PARTICIPANTS Healthy blood donors. INTERVENTIONS Whole blood from healthy donors was spiked with ticagrelor or aspirin (used as a positive control). MAIN OUTCOME MEASURES Platelet aggregation was investigated with impedance aggregometry on whole blood [expressed in ohms (V)] and light transmission aggregometry (expressed in %) on platelet-rich plasma using ADP or arachidonic acid as agonists for ticagrelor or aspirin, respectively. Platelet supplementation was defined as the addition of washed platelet suspension increasing at least 60% of whole blood platelet count. RESULTS Ticagrelor (3.25 mM) inhibited ADP-induced platelet aggregation compared with control either in whole blood (2 vs. 13 V, P < 0.05) or in platelet-rich plasma (15 vs. 75% P < 0.05). Aspirin (25 mM) inhibited arachidonic acid-induced aggregation (1 vs. 7.5 V, P < 0.05 in whole blood and 5 vs. 77.5%, P = 0.01 in platelet-rich plasma). Platelet supplementation completely restored arachidonic acid-induced platelet aggregation in whole blood (10 vs. 1 V, P = 0.008) and platelet-rich plasma (73 vs. 5%, P < 0.01) in aspirin-treated samples, whereas it failed to correct ADP-induced aggregation (2 vs. 2 V in whole blood and 13.5 vs. 15% in platelet-rich plasma, P > 0.05) in ticagrelor-treated samples. We also report a case of a ticagrelor-treated patient in whom platelet transfusion failed to restore ADP-induced platelet aggregation. CONCLUSION Platelet supplementation restored platelet aggregation in aspirin-spiked but not in ticagrelor-spiked samples. These results do not support the use of platelet transfusion to reverse the effects of ticagrelor.