Mate Petricevic

Assessment of platelet function by whole blood impedance aggregometry in coronary artery bypass grafting patients on acetylsalicylic acid treatment may prompt a switch to dual antiplatelet therapy

Residual platelet reactivity (RPR) following coronary artery bypass grafting (CABG) might be related to thrombotic complications and major ischemic cardiac events. The aim of this study was to evaluate the changes in platelet reactivity monitored pre- and postoperatively using multiple-electrode aggregometry (MEA) and to propose an alternative therapeutic approach in a subgroup of patients with postoperative RPR. Ninety-nine patients undergoing elective CABG were enrolled in the study, of whom 41 (41.4%) were diabetic. Preoperatively, all patients received 100 mg acetylsalicylic acid (ASA), with 47 of 99 (47.4%) patients receiving an additional 75 mg clopidogrel (CLO). The blood samples were drawn the day before surgery, and on the first and 4th postoperative day. Platelet count and fibrinogen level were documented, as well as type and daily dose of antiplatelet therapy (APT) received pre- and postoperatively. Multiple-electrode aggregometry using tests based on arachidonic acid (ASPI test) and adenosine diphosphate (ADP test) was performed on the day before and 4 days after surgery. Preoperatively, we detected 31 of 99 (31.3%) patients with RPR (ASPI > 30 AUC). Platelet count correlated with both the ASPI (P = 0.03) and ADP (0.002) tests. Fibrinogen correlated with ADP test values (P < 0.001) and was found to have a higher level in the diabetic subgroup (P = 0.01). In comparison with preoperative results, we detected higher values of ASPI test postoperatively (P = 0.04), with 46 of 99 (46.5%) patients having RPR despite a higher dose of 300 mg ASA being administered. Postoperatively, diabetic patients had higher ASPI test values (P = 0.01), and a higher proportion of patients with RPR compared with the nondiabetic subgroup (58.5 vs 38%, P = 0.04). The subgroup of patients with detected ASPI >30 AUC at the 4th postoperative day consequently received as a part of our clinical routine an additional 75 mg CLO per day, in terms of platelet inhibition optimization. Multiple-electrode aggregometry can recognize patients with RPR during both the pre- and post-CABG period. Postoperatively administered ASA (300 mg) did not sufficiently inhibit platelet aggregation in 46.5% of post-CABG patients. In this group of patients a switch to dual APT should be considered.

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639]

B ackgroundCoronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive.The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events.MethodsPatients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded.DiscussionThis will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management.This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).

Aortic Root Vasculitis Associated With Cogan's Syndrome

Cogans syndrome is characterized by nonsyphilitic interstitial keratitis and an audiovestibular disorder resembling Meniere disease. We report a patient with progressive congestive heart failure due to massive aortic and mitral insufficiency coupled with aortitis leading to an ascending aortic aneurysm. The patient underwent successful aortic root replacement and mitral valve repair.

The predictive value of platelet function point-of-care tests for postoperative blood loss and transfusion in routine cardiac surgery: a systematic review.

Excessive bleeding after cardiopulmonary bypass (CPB) operations remains to be a persistent problem and weak platelet function certainly contributes to bleeding diathesis. Antiplatelet therapy (APT) is an integral component of perioperative management in patients undergoing cardiac surgery procedures, both with and without use of CPB. In addition to individual variability in platelet function, different preoperative APT administration/discontinuation management further affects platelet function, which in turn may reflect bleeding tendency. However, the impact of drug-induced platelet inhibition on early postoperative bleeding extent remains difficult to predict. Herein, we reviewed the available evidence on the association between platelet function testing values and the extent of bleeding and transfusion requirements in early perioperative period. Currently, the association between platelet function measured by ex vivo assay and the occurrence of bleeding events remains uncertain. The intent of this review is to provide comprehensive literature insight into published evidence, investigating the possibility of platelet function tests to predict bleeding extent as well as transfusion requirements in cardiac surgery patients.

Results of extracorporeal life support implementation in routine clinical practice: single center experience

Aim To describe our experience in the clinical application of extracorporeal life support (ECLS) and analyze whether ECLS leads to acceptable clinical outcomes in patients with cardiac failure. Methods Data from clinical database of University Hospital Center Zagreb, Croatia, on 75 patients undergoing ECLS support from 2009 to 2014 due to cardiac failure were retrospectively analyzed. Outcomes were defined as procedural and clinical outcomes. ECLS as a primary procedure and ECLS as a postcardiotomy procedure due to inability to wean from cardiopulmonary bypass were analyzed. Results ECLS was used in 75 adult patients, and in 24 (32%) of those procedural success was noted. ECLS was implemented as a primary procedure in 36 patients and as a postcardiotomy procedure in 39 patients. Nine out of 39 (23.08%) patients had postcardiotomy ECLS after heart transplantation. Bleeding complications occurred in 30 (40%) patients, both in primary (11/36 patients) and postcardiotomy group (19/39 patients). ECLS was established by peripheral approach in 46 patients and by central cannulation in 27 patients. In 2 patients, combined cannulation was performed, with an inflow cannula placed into the right atrium and an outflow cannula placed into the femoral artery. Eleven patients treated with peripheral approach had ischemic complications. Conclusion ECLS is a useful tool in the treatment of patients with refractory cardiac failure and its results are encouraging in patients who otherwise have an unfavorable prognosis.

Bleeding and Thrombotic Events in Patients Undergoing Mechanical Circulatory Support: A Review of Literature

Bleeding and thrombotic events are among the most common complications detected in patients with mechanical circulatory support (MCS). Herein, we reviewed the available evidence on the prevalence, etiology, and management of bleeding and thrombotic events in patients following MCS procedures, such as implantation of both intra- and paracorporeal devices that generate either pulsatile or nonpulsatile flow. Extracorporeal life support procedures providing support to the failing heart and lungs were also reviewed. Most bleeding and thromboembolic events occur despite appropriate hemostatic and anticoagulation management based on conventional coagulation laboratory parameters. Prevalence of bleeding events in this population ranges between 5 and 81%. Wide range in prevalence of bleeding reported in literature may be explained by different devices with different anticoagulation protocols being used, as well as different definitions of bleeding outcomes. Although bleeding events are more common than thromboembolic events, the consequences of thrombotic events are often detrimental. Management of bleeding events remains challenging and measures to prevent and treat bleeding events are often followed by thromboembolic events. Therefore, a personalized approach based on point-of-care hemostatic tests and adjusted to device type and patient comorbidities is therefore warranted. To provide advanced understanding of hemostatic disturbances during MCS, prospective trials focused on bleeding and thromboembolic events as primary endpoints should be conducted. Better understanding of the underlying pathophysiology and a shift towards a personalized approach based on functional point-of-care hemostatic properties assessment may provide more favorable clinical outcomes. This should, however, be coupled with further technological improvements providing better device surface hemocompatibility as interaction between blood and device surface affects the hemostatic equilibrium.

Diagnostic accuracy of central venous saturation in estimating mixed venous saturation is proportional to cardiac performance among cardiac surgical patients

PURPOSE Advanced hemodynamic monitoring in cardiac surgery translates into improvement in outcomes. We evaluated the relationship between central venous (ScvO2) and mixed venous (SvO2) saturations over the early postoperative period. The adequacy of their interchangeability was tested in patients with varying degrees of cardiac performance. METHODS In this prospective observational study, we evaluated 156 consecutive cardiac surgical patients in an academic center. The ScvO2 and SvO2 data were harvested from 468 paired samples taken preoperatively (T0), after weaning from cardiopulmonary bypass (T1) and on postoperative day 1 (T2). RESULTS The relationship between ScvO2 and SvO2 was inconsistent, with inferior correlations in patients with lower cardiac indices (CI) (Pearson r(2) = 0.37 if CI ≤2.0 L/min per square meter vs r(2) = 0.73 if CI >2.0 L/min per square meter, both P < .01). Patients with lower CI also had wider 95% limits of agreement between SvO2 and ScvO2. The proportion of patients with a negative SvO2-ScvO2 gradient increased over time (48/156 [31%] at T0 to 73/156 [47%] at T2; P < .01). This subgroup more frequently required inotropes at T2 than patients with a positive SvO2-ScvO2 gradient (odds ratio, 6.46 [95% confidence interval, 0.81-51.87], P = .06) and also had higher serum lactate levels (1.5 ± 0.8 vs 1.0 ± 0.4; P < .01). CONCLUSIONS The diagnostic accuracy of ScvO2 for estimating SvO2 is proportional to cardiac performance. A negative SvO2-ScvO2 gradient at T2 correlated with inotropic support requirement, higher operative risk score, age, lactate level, and duration of cardiopulmonary bypass.

Impact of aspirin resistance on antiplatelet therapy management after coronary artery surgery

Dual antiplatelet therapy (APT) provides incremental platelet inhibition compared with either agent alone and more effective suppression of adverse ischaemic events [2]. This finding is confirmed by Awidi and coworkers who found that the combination of aspirin and clopidogrel had greater inhibitory effects on platelet aggregation than either agent alone in patients with coronary artery disease [3]. In our opinion, the addition of clopidogrel in the group of patients with AR inevitably affected both the observed clinical outcomes and the decrease in AR proportion. Following CAS, extensive evidence supports the use of aspirin, in doses of 100–325 mg/day, to be administered postoperatively and continued indefinitely [4]. A daily 100 mg dose of aspirin administered postoperatively in a study by Wang et al. [1], allows the possibility of different APT management strategies. For example, a stepwise increase in the aspirin dose with a subsequent platelet function assessment could probably bring a further decrease in the AR proportion and therefore, eliminate the need for dual APT. However, it still remains unclear, whether an aspirin dose increase would be superior to dual APT, in the context of a clinical outcome. Of note, a meta-analysis by Snoep et al. showed an overall prevalence of 21% of laboratory-defined clopidogrel low response [5]. We believe that these two different APT approaches should be evaluated in a large cohort randomized trial with an outcome evaluation of both ischaemic and bleeding events. The authors hypothesized that the Chinese population is more sensitive to aspirin therapy and presented no AR at a 6-month follow-up. It would be interesting if the authors analyzed the bleeding event occurrence at the 6-month follow-up in the group of patients on dual APT. APT management in cases of AR should be individually tailored, with aspirin dosage stepwise increased (up to 325 mg/day), and clopidogrel administration in cases of AR to high aspirin doses. Temporary AR requires temporary APT adjustment. The duration and intensity of the APT adjustment should be tailored according to drug specific platelet function tests in order to minimize both ischaemic and bleeding events. In conclusion, it is difficult to investigate by what amount the laboratory AR corresponds to the clinical AR. Prospective studies, with a large study sample necessitated by the infrequency of adverse ischaemic events, must determine the optimal threshold for AR, taking into consideration both the laboratory and clinical outcome findings.

2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery

Authors/Task Force Members: Christa Boer (EACTA Chairperson)(Netherlands), Michael I. Meesters (Netherlands), Milan Milojevic (Netherlands), Umberto Benedetto (UK), Daniel Bolliger (Switzerland), Christian von Heymann (Germany), Anders Jeppsson (Sweden), Andreas Koster (Germany), Ruben L. Osnabrugge (Netherlands), Marco Ranucci (Italy), Hanne Berg Ravn (Denmark), Alexander B.A. Vonk (Netherlands), Alexander Wahba (Norway), Domenico Pagano (EACTS Chairperson)(UK),. Document Reviewers: Moritz W.V. Wyler von Ballmoos (USA), Mate Petricevic (Croatia), Arie Pieter Kappetein (Netherlands), Miguel Sousa-Uva (Portugal), Georg Trummer (Germany), Peter M. Rosseel (Netherlands), Michael Sander (Germany), Pascal Colson (France), Adrian Bauer (Germany).

Influence of Transiently Increased Nutritional Risk on a Left Ventricle Myocardial Mass Assessed by Echocardiography

Background/Aim: Metabolic derangements due to increased nutritional risk lead to catabolism and loss of proteins, muscle tissue and eventually mass of parenchymatous organs. The aim of our study was to assess whether transitory nutritional risk after heart surgery influences on the left ventricle myocardial mass (LVMM), assessed by echocardiography. Methods: Consecutive sample of patients scheduled for cardiovascular rehabilitation, in period 0-3 months after surgery. Nutritional risk screening (NRS) was analyzed using the NRS-2002 tool. Results: Study sample included 330 patients after heart surgery for ischemic 186 (56.4%); valvular 91 (27.6%) and valvular plus ischemic 53 (16.1%) heart disease. Age was 65.5 ± 10.6 (range 23-84) and there were more male patients than female - 240 (72.7%) and 90 (27.3%), respectively. The percentage of unintentional loss of weight was 10.8 ± 3.4%, in range 0-23.81%, whereas NRS-2002 was 4.4 ± 1.1. LVMM was 218.7 ± 65.9 g vs. 252.3 ± 51.7 (p = 0.015); for patients with increased nutritional risk and controls, respectively. There was no significant correlation of LVMM with NRS-2002, while the percentage of unintentional loss of weight displayed only weakly inverse correlation (Rho CC = -0.197; p = 0.007). LVMM also correlated significantly with body mass index (Rho CC = 0.247; p < 0.001) and waist-to-hip ratio (Rho CC = 0.291; p < 0.001). In conclusion, LVMM was found to decrease slightly in the period of increased nutritional risk, following heart surgery. Changes in LVMM are partially consequences of systemic catabolic response, as well as anthropometric changes due to unintentional loss of weight.