Lucija Svetina

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).

Significance of clinical stage, extent of surgery and outcome in cutaneous squamous cell carcinoma of the head and neck

The authors analyzed a new clinical staging system and its correlation with pathologic findings and patient survival. Patients were eligible for inclusion in this longitudinal retrospective cohort study if they had cutaneous squamous cell carcinoma on the head or neck, underwent surgery and had a minimum 3 year follow-up. The primary study variable was using a new clinical staging system. Secondary variables included the parotid as a predictor of metastatic spread to the lymphatic nodes in the neck and primary lesion histopathologic traits. The outcome variable was patient survival. Associations between variables were assessed using Fishers exact test, Mann-Whitney test, Kaplan-Meier method and Mantel log-rank test. p<0.05 was considered significant. The sample comprised 103 patients. Regional metastatic disease was found in 24 patients. Histopathological analysis showed a higher frequency of neck metastatic disease if the parotid was positive for metastases (p=0.022). An extended staging system showed significant correlation between survival rate and substages (p=0.0105). Perineural invasion was a negative prognostic factor (p=0.0151). The results of this study suggest that combining curative parotidectomy and elective neck dissection could be beneficial in high risk patients. Both neck and parotid metastases should be included in the clinical and histological N classification.

Pretransplant and perioperative predictors of early heart transplantation outcomes

Aim To identify predictors of 3-month mortality after heart transplantation in a Croatian academic center. Methods A retrospective review of institutional database identified 117 heart transplantations from January 2008 to July 2014. Two children <14 years were excluded from the study. The remaining 115 patients were dichotomized into survivors and non-survivors adjudicated at 3-months postoperatively, and their demographic, clinical, and longitudinal hemodynamic data were analyzed. Results 3-month survival after heart transplantation was 86%. Non-survivors were older (59 ± 8 vs 50 ± 14 years, P = 0.009), more likely to have previous cardiac surgery (44% vs 19%; odds ratio [OR] 3.28, 95% confidence interval [CI] 1.08-9.90; P = 0.029), lower body mass index (BMI) (25 ± 4 vs 28 ± 2 kg/m2, P = 0.001), and be diabetics (44% vs 23%; OR 2.57, 95% CI 0.86-7.66; P = 0.083). Creatinine clearance was marginally superior among survivors (59 ± 19 vs 48 ± 20 mL/min, P = 0.059). Donor age and sex did not affect outcomes. Non-survivors were more likely to have had ischemic cardiomyopathy (69% vs 32%, P = 0.010). Postoperative utilization of epinephrine as a second line inotropic agent was a strong predictor of mortality (63% vs 7%; OR 21.91; 95% CI 6.15-78.06; P < 0.001). Serum lactate concentrations were consistently higher among non-survivors, with the difference being most pronounced 2 hours after cardiopulmonary bypass (9.8 ± 3.5 vs 5.2 ± 3.2 mmol/L, P < 0.001). The donor hearts exhibited inferior early hemodynamics in non-survivors (cardiac index 3.0 ± 1.0 vs 4.0 ± 1.1 L/min/m2, P = 0.001), stroke volume (49 ± 24 vs 59 ± 19 mL, P = 0.063), and left and right ventricular stroke work indices (18 ± 8 vs 30 ± 11 g/beat/m2, P < 0.001 and 5 ± 3 vs 7 ± 4 g/beat/m2, P = 0.060, respectively). Non-survivors were more likely to require postoperative re-sternotomy (50% vs 12%; OR 7.25, 95% CI 2.29-22.92; P < 0.001), renal replacement therapy (RRT) (69% vs 9%; OR 22.00, 95% CI 6.24-77.54; P < 0.001), and mechanical circulatory assistance (MCS) (44% vs 5%; OR 14.62, 95% CI 3.84-55.62; P < 0.001). Binary logistic regression revealed recipient age (P = 0.024), serum lactates 2 hours after CPB (P = 0.007), and epinephrine use on postoperative day 1 (P = 0.007) to be independently associated with 3-month mortality. Conclusion Pretransplant predictors of adverse outcome after heart transplantation were recipient age, lower BMI, ischemic cardiomyopathy, reoperation and diabetes. Postoperative predictors of mortality were inferior donor heart hemodynamics, epinephrine use, and serum lactate concentrations. Non-survivors were more likely to require re-sternotomy, MCS, and RRT.

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.

Postoperative Atrial Fibrillation Is Associated With High On-Aspirin Platelet Reactivity

BACKGROUND Atrial fibrillation (AF) contributes to a prothrombotic state through platelet activation. It is unclear whether increased platelet aggregability in patients with AF is caused by the underlying cardiovascular condition rather than the arrhythmia per se. We investigated the effect of postoperative atrial fibrillation (POAF) on platelet reactivity after coronary artery bypass grafting (CABG). METHODS This study is a post hoc analysis from a randomized controlled trial (ClinicalTrials.gov: NCT01159639) based on patients undergoing elective primary CABG. Patients were dichotomized according to POAF. Postoperative platelet function testing with arachidonic acid as the platelet agonist (ASPI test) was used to define high on-aspirin platelet reactivity (HAPR). ΔASPI presented the difference between pre- and postoperative ASPI test values. To account for the isolated effect of POAF on platelet reactivity, a propensity score analysis was applied. RESULTS Overall incidence of POAF was 23% (92 of 398 patients). HAPR was detected in 54% (214 of 398) of patients. HAPR was more prevalent among patients with POAF when compared with patients without POAF (64.1% versus 50.7%; odds ratio [OR], 1.74; 95% confidence interval [CI], 1.08-2.82; p = 0.023). The propensity score model produced a subcohort of patients that was well balanced for comorbidities. When compared with the matched group without POAF, the POAF group maintained its prevalence for HAPR (64.1% versus 45.7%; OR, 2.13; 95% CI, 1.18-3.85; p = 0.012) and had greater ΔASPI values (15.0 [IQR, 0.0-36.0] vs 8.0 [IQR, -5.5-19.5]; p = 0.030). CONCLUSIONS The main finding of our study indicates there is added platelet activation in patients with POAF after CABG before and after controlling for pathologic conditions through propensity matching. The present study does not prove a causal association between POAF and HAPR.

Definition of aspirin resistance using whole blood impedance aggregometry in patients undergoing coronary artery surgery: methodological challenges and outcome improvement opportunities

Methods Prospective observational trial at University Hospital Center Zagreb enrolled 131 patients scheduled for CABG, and divided them into 4 groups with respect to preoperative antiplatelet therapy (APT). Group 1 received 100 mg ASA per day, Group 2 100 mg ASA + 75 mg clopidogrel per day, Group 3 75 mg clopidogrel per day, and Group 4 did not receive any APT. MEA with ASPI test (sensitive to ASA) and ADP test (sensitive to clopidogrel) was performed prior to surgery. In Group 1, patients were characterized as ASA resistant if their ASPI test value exceeded the 75th percentile distribution. Results Study enrolled 131 patients. Significant differences both in the ASPI (p<0.001) and the ADP test (p=0.038) were observed between patients in different APT groups. In Group (1) ASPI test value of 30 AUC presented 75th percentile of distribution, thus indicating ASA resistance. Group 2 patients had slightly lower ADP test values, but no significant difference occurred (mean 60.05 vs. 63.32 AUC, p=0.469). In Group 1 and 2, significant correlations between the ADP test and both, platelet count (r=0.347, p<0.001) and fibrinogen level (r=0.364, p<0.001) were observed.

The change in pulmonary vascular resistance after left ventricular assist device implantation - the predictive role of platelets revisited

E-mail: marijan.pasalic@yahoo.com Purpose: While analyzing the group of patients implanted with a left ventricular assist device (LVAD) at our institution to verify which of the preand postoperative factors constitute the optimal survival outcome predictors, we determined a significant increase in postoperative pulmonary vascular resistance (PVR) values in the expired patients1. The aim of this study was to further analyze the data in order to determine which of the preoperative factors were related to the aforementioned increase in postoperative PVR values. Methods: For the 20 patients (18 M, 2 F; mean age 58.7±8.3 years) that have been implanted with an LVAD in our institution during the past 2 years, preimplantation echocardiography, right heart catheterization (RHC) and laboratory data were collected and compared according to the values of the postimplantation PVR. The groups were compared by using the adequate statistical test (t-test, Mann Whitney U test, statistical significance set at 0.05). Correlation analysis and linear regression were performed. Results: Among the 20 patients, 14 had postoperative RHC data and 4 of them were proven to have elevated PVR values (>2.4 WU). When comparing the pts. with elevated to those with normal PVR values, no significant difference was found neither in the RV function (FAC 33±7% vs 22±12%, TAPSE 1,0±0,7 cm vs 1.6±0.5 cm, NS), nor in the RV and LV dimensions (RVIDd 34±9 mm vs 35±12 mm, LVIDd 65±10 mm vs 73±9 mm). The borderline significance was found in the left ventricular EF (28±3% vs 19±8%, p=0.06) and the degree of the MR (median values 1 vs 2, p=0.05). The preoperative RHC parameters were not found to be predictive of changes in postoperative PVR (preoperative PVR 4,2±3,4 vs 3,4±1,5 WU, C.I. 1,8±0,7 vs 1,9±0,4 L/min/m, TPG 14±11 vs 13±4 mmHg and RVSWI 11,4±2,2 vs 8,9±2,1, NS). As for the laboratory values, only the platelet count significantly differed between the groups (128 ±73 vs 246±65 E3/mm, p<0.05). The correlation analysis showed a strong negative correlation between the platelet count and postoperative PVR values (r=-0,761, p<0.01). The linear regression verified the following relationship between the variables PVR=6,247-0,017xPLT, p<0.01). Conclusion: These preliminary data show that the platelet count is a significant predictor of the postoperative PVR values in patients with an LVAD (a previously shown survival predictor1). Further investigation will be conducted to explain the role of platelets in the etiology of PVR in our group of pts.

Utilization of single-use gowns reduces the incidence of postoperative infections

Background Gowns and drapes are used widely in health care facilities. Gowns have been used to minimize the risk of disease acquisition by health care providers, to reduce the risk of patient-to-patient transmission, and to maintain sterility during invasive procedures. The aim of this prospective randomized study is to compare the ability of single-use and reusable surgical gowns to protect against the infections during surgical procedures in the Department of Cardiac Surgery University Hospital Center Zagreb.

Clopidogrel and aspirin administration management prior to coronary artery surgery requires an individual approach

We read with great interest the recently published retrospective study by Miceli et al.[1]. Using multivariable analysis, the authors found that administration of clopidogrel + aspirin within 5 and 2 days, respectively, before coronary artery surgery, was an independent risk factor for postoperative myocardial infarction (MI), re-exploration for bleeding, blood loss and blood transfusions.