A Novel Three-Dimensional Approach Towards Evaluating Endomyocardial Biopsies for Follow-Up After Heart Transplantation: X-Ray Phase Contrast Imaging and Its Agreement With Classical Histopathology.

Endomyocardial biopsies are the gold standard for surveillance of graft rejection following heart transplantation, and are assessed by classical histopathology using a limited number of previously stained slices from several biopsies. Synchrotron propagation-based X-ray phase contrast imaging is a non-destructive method to image biological samples without tissue preparation, enabling virtual 2D and 3D histopathology. We aimed to show the feasibility of this method to assess acute cellular rejection and its agreement to classical histopathology. Right ventricular biopsies were sampled from 23 heart transplantation recipients (20 males, mean age 54±14 years) as part of standard follow-up. The clinical diagnosis of potential rejection was made using classical histopathology. One additional study sample was harvested and imaged by X-ray phase contrast imaging, producing 3D datasets with 0.65 µm pixel size, and up to 4,320 images per sample. An experienced pathologist graded both histopathological and X-ray phase contrast images in a blinded fashion. The agreement between methods was assessed by weighted kappa, showing substantial agreement (kappa up to 0.80, p < 0.01) between X-ray phase contrast imaging and classical histopathology. X-ray phase contrast imaging does not require tissue processing, allows thorough analysis of a full myocardial sample and allows identification of acute cellular rejection.

Transcatheter Aortic Valve Implantation Induces Transient Drop in Platelet Reactivity.

ABSTRACT: Although recent studies described platelet reactivity (PR) changes in days after transcatheter aortic valve implantation (TAVI), precise time course and duration of these changes have not been fully investigated. The aim of this study was to investigate PR pattern during and after TAVI in multiple time points. Study included 40 consecutive patients undergoing TAVI. All patients underwent the procedure on dual antiplatelet therapy. PR was measured in 7 time points: before induction of anesthesia (T1), after heparin administration (T2), 10 minutes after initial valve implantation (T3), at the end of procedure (T4), and on 3rd, 6th, and 30th postoperative day (T5-T7). PR was measured using impedance aggregometer using 3 different platelet aggregation agonists (arachidonic acid in ASPItest, adenosine diphosphate in ADPtest and thrombin receptor activating peptide 6 in TRAPtest). All patients underwent successful TAVI procedure. Mean PR on T1 was 22.9 ± 23.0 U for ASPItest, 40.5 ± 23.7 U for ADPtest and 91.7 ± 32.5 U for TRAPtest. There was no significant difference in PR on T2. On T3, significant reduction of PR in all 3 tests was observed [ASPI 10.4 ± 11.6 U (P = 0.001), ADP 24.2 ± 14.1 U (P < 0.001) and TRAP 69.3 ± 26.6 U (P < 0.001)]. PR nadir for all tests was reached on T5, with subsequent PR incline. PR values in all tests returned to baseline levels on T7. Our results show that successful TAVI procedure induces transient decrease in PR regardless of the platelet activation pathway.

Impact of Continuous P2Y12 Inhibition Tailoring in Acute Coronary Syndrome and Genetically Impaired Clopidogrel Absorption.

Clopidogrel is still widely used in acute coronary syndrome despite the development of more potent P2Y12 inhibitors. Previously, we conducted a trial that evaluated serial clopidogrel dose adjustment based on platelet function testing in acute coronary syndrome patients with initial high on-treatment platelet reactivity (HTPR). In this substudy, we performed post hoc analysis of the effect of ABCB1 genetic variants C3435T and G2677T/A on platelet inhibition and outcomes. There were no differences in the proportion of HTPR patients among C3435T carriers and noncarriers in both interventional and control group. G2677T carriers expressed significantly higher proportion of HTPR pattern throughout 12-month follow-up in the control group with no difference in the interventional group. There was no difference in ischemic outcomes between C3435T and G2677T carriers and noncarriers in both groups of patients. The results indicate that ABCB1 genotyping is not useful to guide clopidogrel therapy tailoring to improve high-risk patient management.

Severe bleeding caused by piperacillin/tazobactam-induced platelet dysfunction
.

OBJECTIVE: Piperacillin/tazobactam (TZP ) is commonly used against multi-resistant nosocomial Pseudomonas infections. While TZP-induced thrombocytopenia is a well-known and easily diagnosed complication, we herein present an unusual case of spontaneous TZP-induced bleeding caused by platelet dysfunction. CASE SUMMARY: A 73-year-old-man experienced severe pulmonary hemorrhage and bloody diarrhea during the treatment with TZP for Pseudomonas aeruginosa ventilator-associated pneumonia. While both platelet count and coagulation tests were normal, platelet functional test revealed severely impaired ADP-dependent platelet aggregation. CONCLUSION: Platelet dysfunction is a little-known mechanism of TZP-induced bleeding. This is the second reported case of TZP-related bleeding that has been attributed to platelet dysfunction, and the first case report that has not been associated with surgery. While thrombocytopenia is easily recognized, this form of TZP-induced bleeding can be detected only by platelet functional tests.

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.

Dynamic tricuspid valve stenosis induced with a pacemaker lead: a case report.

Isolated severe tricuspid valve stenosis due to an endocardial pacemaker lead is extremely rare, and is usually caused by either fibrosis of a perforated or lacerated leaflet, or fibrotic adherence between the lead and the valvular apparatus. Reported cases typically include clinical manifestations of both systemic venous stasis and low cardiac output. The case is presented of a 20-year-old female with a surgically repaired congenital heart disease who developed severe tricuspid stenosis at six years after the implantation of a DDD pacemaker. Unexpectedly, the patient had no signs of venous stasis and suffered only from exercise intolerance. Right heart catheterization under fluoroscopic guidance revealed an atrial lead forming a loop at the level of the tricuspid valve. A paradoxical inspiratory decrease in the transvalvular diastolic gradient, caused by the caudal heart motion and straightening of the loop during inspiration, was noted. Such a dynamic nature with a temporary inspiratory relief of the obstruction may explain the partial clinical presentation of tricuspid stenosis in this case. The lead was removed and the tricuspid valve repaired surgically, after which the patient's recovery was uneventful with normalization of exercise tolerance.

Serial clopidogrel dose adjustment after platelet function testing improves outcome of acute coronary syndrome patients undergoing percutaneous coronary intervention with high on-treatment platelet reactivity.

High on-treatment platelet reactivity (HTPR) on clopidogrel correlates with adverse outcomes in patients treated with percutaneous coronary intervention (PCI). Whether HTPR is a modifiable risk factor for future events is not clear. We evaluated the effect of serial clopidogrel dose adjustment based on platelet function testing (PFT) during 12 months of dual antiplatelet therapy (DAPT) using Multiplate) analyzer in patients with HTPR after PCI in acute coronary syndrome on clinical outcome. Eighty-seven patients were randomized to interventional (n = 43) and control group (n = 44). Blood samples for PFT were drawn at day 1, 2, 3, 7, 30 and at month 2, 3, 6, 9 and 12. Clopidogrel dose was modified at each point of PFT in the interventional group with patients taking up to two additional 600 mg loading doses and a range of 75-300 mg maintenance dose to achieve and maintain optimal platelet reactivity (19-46 U). The incidence of the primary endpoint (composite of cardiovascular death, non-fatal myocardial infarction, target vessel revascularization and ischemic stroke) was significantly higher in the control group (36.3 vs. 16.2%; p = 0.034). There were no differences in total bleeding events (6.8 vs. 4.6%, p = ns). Patients in the interventional group maintained better P2Y12 inhibition during follow-up. We hypothesize that targeting the therapeutic window of platelet reactivity continuously throughout DAPT by dose adjustment of P2Y12 inhibitor may lead to better platelet reactivity control, and thus reduce the rate of ischemic complications in this high risk group of patients.

Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis.

Development of cardiac allograft vasculopathy represents the major determinant of long-term survival in patients after heart transplantation. Due to graft denervation, these patients seldom present with classic symptoms of angina pectoris, and the first clinical presentations are progressive heart failure or sudden cardiac death. Although coronary angiography remains the routine technique for coronary artery disease detection, it is not sensitive enough for screening purposes. This is especially the case in the first year after transplantation when diffuse and concentric vascular changes can be easily detected only by intravascular ultrasound. The treatment of the established vasculopathy is disappointing, so the primary effort should be directed toward early prevention and diagnosis. Due to diffuse vascular changes, revascularization procedures are restricted only to a relatively small proportion of patients with favorable coronary anatomy. Percutaneous coronary intervention is preferred over surgical revascularization since it leads to better acute results and patient survival. Although there is no proven long-term advantage of drug-eluting stents for the treatment of in-stent restenosis, they are preferred over bare-metal stents. Severe vasculopathy has a poor prognosis and the only definitive treatment is retransplantation. This article reviews the present knowledge on the pathogenesis, diagnosis, treatment, and prognosis of cardiac allograft vasculopathy.

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/m(2), 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/m(2), 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/m(2), P<0.001 and 5±3 vs 7±4 g/beat/m(2), 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.

The addition of Cytosorb in patients on VA-ECMO improves urinary output and ICU survival.

INTRODUCTION: The aim of this study was to analyze the efficiency of CytoSorb adsorber in patients presenting with cardiogenic shock and treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: Sixteen patients put on VA ECMO due to cardiogenic shock were included, stratified according to the use of Cytosorb adsorber in the first 24 h and compared across different clinical outcomes. RESULTS: Significantly lower vasopressor doses were required among patients treated with Cytosorb at the initiation and before weaning from ECMO. Furthermore, these patients showed significantly higher urine output before weaning and lower lactate levels during the extracorporeal support. Finally, the mortality rate was lower among the Cytosorb therapy group (22.2% vs 57.1%). CONCLUSION: While a decrease in vasopressor doses was already associated with CytoSorb use, this is the first study showing an increase in urinary output and a trend towards better survival among patients on VA ECMO treated with CytoSorb.

Cardiac arrest in a patient with Ebstein's anomaly without accessory pathways.

We describe a case report of a patient with cardiac arrest and Ebstein's anomaly. This case report shows us necessity for arrhythmia evaluation and sudden death risk stratification even in asymptomatic patients. Prophylactic ICD implantation in this patient population is limited to observational studies and the selection of patients is impeded by the absence of randomized trials and weak predictors.

[Croatian Society for Haematology and Transfusion Medicine Guidelines on the diagnosis and management of heparin induced thrombocytopenia (HIT)]. / Smjernice Hrvatskog drustva za hematologiju i transfuzijsku medicinu u dijagnosticko-terapijskom postupku za trombocitopeniju izazvanu heparinom (HIT).

Heparin induced thrombocytopenia (HIT) is a serious complication of heparin administration. In the last decade, this clinical syndrome has come into the focus of interest, primarily because of the severe thromboembolic complications that may lead to lethal outcome. In addition, great improvements have been made in the treatment with direct thrombin inhibitors and in laboratory diagnosis of HIT. As guidelines for diagnostic and management of HIT upgrade the quality of patient treatment, activities for their development have been launched in the Republic of Croatia. Based on British Committee for Standards in Haematology (BCSH) recommendations on diagnostic and treatment of HIT from 2006, activities for the introduction of new assays for anti-heparin antibodies were launched in 2008 and 2009, including algorithm of laboratory testing for HIT, sheet for clinical assessment of HIT (4T score), and education oftransfusiologists and clinicians. Upon evaluation of the results collected during one-year period, the Croatian Society of Haematology and Transfusion Medicine nominated a task force for the development of guidelines for HIT in January 2010. Following wide-ranging discussion, the guidelines were adopted in May 2011.

Improved survival of left ventricular assist device carriers in Europe according to implantation eras: results from the PCHF-VAD registry.

AIMS: Temporal changes in patient selection and major technological developments have occurred in the field of left ventricular assist devices (LVADs), yet analyses depicting this trend are lacking for Europe. We describe the advances of European LVAD programmes from the PCHF-VAD registry across device implantation eras. METHODS AND RESULTS: Of 583 patients from 13 European centres in the registry, 556 patients (mean age 53 ± 12 years, 82% male) were eligible for this analysis. Patients were divided into eras (E) by date of LVAD implantation: E1 from December 2006 to December 2012 (6 years), E2 from January 2013 to January 2020 (7 years). Patients implanted more recently were older with more comorbidities, but less acutely ill. Receiving an LVAD in E2 was associated with improved 1-year survival in adjusted analysis (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.98; p = 0.043). LVAD implantation in E2 was associated with a significantly lower chance of heart transplantation (adjusted HR 0.40, 95% CI 0.23-0.67; p = 0.001), and lower risk of LVAD-related infections (adjusted HR 0.64, 95% CI 0.43-0.95; p = 0.027), both in unadjusted and adjusted analyses. The adjusted risk of haemocompatibility-related events decreased (HR 0.60, 95% CI 0.39-0.91; p = 0.016), while heart failure-related events increased in E2 (HR 1.67, 95% CI 1.02-2.75; p = 0.043). CONCLUSION: In an analysis depicting the evolving landscape of continuous-flow LVAD carriers in Europe over 13 years, a trend towards better survival was seen in recent years, despite older recipients with more comorbidities, potentially attributable to increasing expertise of LVAD centres, improved patient selection and pump technology. However, a smaller chance of undergoing heart transplantation was noted in the second era, underscoring the relevance of improved outcomes on LVAD support.

[Antiaggregation therapy after percutaneous coronary intervention in a patient with thrombocytopenia: case report]. / Antiagregacijska terapija nakon perkutane koronarne intervencije kod bolesnika s trombocitopenijom--prikaz bolesnika.

Dual antiaggregation (antiplatelet) therapy is mandatory in patients having received a stent during percutaneous coronary intervention. This therapy usually consists of acetylsalicylic acid (100 mg per day) and clopidogrel (75 mg per day) for at least 6 to 12 months (depending on the type of stent). Such therapy has been shown to reduce significantly unwanted clinical events, although slightly increasing the risk of bleeding. Coronary stents must rarely be implanted in patients who have or develop thrombocytopenia. In such patients, the risk of bleeding is increased manifold. On the other hand, the risk of potentially fatal thrombotic events is unknown. In this case report, we present a patient who developed thrombocytopenia shortly (one month) after the stent had been implanted. After thorough clinical workup, we could not find the remediable cause of thrombocytopenia. Because of the potential of acetylsalicylic acid to induce thrombocytopenia, it was excluded from therapy and a double dose of clopidogrel (150 mg per day) was introduced. Then we decided to evaluate platelet function with the ADP aggregation test (which indicates the degree to which the function of platelets is blocked by clopidogrel) and aspirin resistance test (which indicates the degree to which the function of platelets is blocked by acetylsalicylic acid). In the first set of tests, the patient was shown to be hyperreactive to both substances. We then lowered the dose of clopidogrel to the standard dose and evaluated the function of platelets with the same tests two weeks later and the results were the same. Because the patient was without obvious and laboratory signs of bleeding, we decided not to change the prescribed antiplatelet therapy because of fear from potentially fatal thrombotic events. The use of dual antiplatelet therapy in patients with thrombocytopenia is particularly challenging. We believe that in such patients, firstly, the cause of thrombocytopenia should be sought for by thorough clinical investigation. If not found, as in our patient, tailoring of such therapy should be done using currently available aggregation tests. In such a way, patients could be protected from both excessive bleeding and potentially devastating thrombotic events. Unfortunately, this is a sole example and definite conclusions could only be made on larger studies.

[Aspirin resistance]. / Aspirinska rezistencija.

Although present in pharmacotherapy for more than 100 years, aspirin still represents a cornerstone in the primary and secondary prevention of cardiovascular patients. Despite undoubtful benefit, a certain proportion of patients treated with aspirin develops adverse atherothrombotic events like stent thrombosis, myocardial infarction, stroke and cardiovascular death. In recent years, there is a growing scientific interest concerning the relationship of suboptimal antiplatelet response to aspirin and cardiovascular prognosis that has led to the concept of "aspirin resistance". Besides the absence of uniform definition of aspirin resistance, an important issue in these studies are numerous and poorly standardized laboratory methods that are used in its detection. Despite an increasing number of reports that favour its clinical significance, there are still no expert recommendations for routine assessment of platelet aggregation as well as for modification of antiplatelet doses or regimens in the case of established aspirin resistance.

Lower Platelet Count Following Rabbit Antithymocyte Globulin Induction Is Associated With Less Acute Cellular Rejection in Heart Transplant Recipients.

BACKGROUND: Unlike lymphodepletion, a decrease in platelet count following induction immunosuppressive therapy with polyclonal rabbit antithymocyte globulin (rATG) is deemed as an adverse event. However, this phenomenon may represent a particular rATG antirejection mechanism. METHODS: This retrospective single-center study included 156 patients who received a heart transplant (HTx) between 2010 and 2018. All patients received rATG induction therapy for 5 days. Absolute lymphocyte count (ALC) and platelet counts were assessed on days 0, 7, and 14 following HTx. The primary outcome of the study was the first occurrence of acute cellular rejection (ACR) defined as grade ≥ 1B within 24 months after HTx. RESULTS: Both ALC and platelet counts decreased rapidly after induction. During the 24-month follow-up period, 17% of patients had ACR. Patients with ACR had significantly higher platelet count on day 7 (145 vs 104, P < .001) and higher ALC on day 14 (162 vs 130, P = .035) than those without rejection. Patients in the highest platelet count quartile showed more ACR (50% in quartile 4 vs 0% in quartile 1, P = .006) as well as a higher cumulative total rejection score. Univariate analysis showed that ACR was associated with platelet count on day 7, recipient age, and pretransplant cytomegalovirus IgG serology. In multivariable regression analysis, platelet count on day 7 was the most accurate predictor of ACR. CONCLUSIONS: Lower platelet count after induction with rATG is associated with less ACR. This suggests platelet involvement in antirejection mechanisms of rATG and a possible rationale for targeting platelets in future immunosuppressive strategies.

[Does Lp-PLA2 determination help predict atherosclerosis and cardiocerebrovascular disease?]. / Moze li odredivanje Lp-PLA2 pomoci u predvidanju ateroskleroze i kardiocerebrovaskularnih bolesti?

Thorough control of risk factors is pivotal for cardiocerebrovascular diseases. As classic risk assessment accounts for only 50% of risk variability and due to the role of inflammatory processes in endothelial dysfunction and atherosclerotic plaque rupture, it is necessary to identify new biomarkers for risk prediction. In addition to the inflammatory marker high sensibility C-reactive protein (hs-CRP), lipoprotein associated phospholipase A2 (Lp-PLA2) is gaining increasing significance, since it is directly involved in the pathogenesis of atherosclerotic plaque progression. Lp-PLA2 is highly specific for vascular inflammation, has low biological variability, and plays a causative role in atherosclerotic plaque inflammation. It belongs to the group of intracellular and secretory phospholipase enzymes that can hydrolyze sn-2 phospholipid ester bond of cellular membranes and lipoproteins. Lp-PLA2 enzyme is formed by macrophages and foam cells in atherosclerotic plaque, and is associated primarily with LDL particles in blood. Lp-PLA2 that is bound to LDL is the sole enzyme responsible for hydrolysis of oxidized phospholipids (oxPL) on LDL particles. Lp-PLA2 hydrolyzes oxPL at the surface of lipoproteins, but has weak activity against non-oxPL. Lp-PLA2 is also the enzyme that hydrolyzes oxPL on HDL particles, where it may have a role in the antioxidative function of HDL. The distribution of Lp-PLA2 between LDL and HDL particles depends on the extent of Lp-PLA2 glycosylation, which may affect the activity of Lp-PLA2 in plasma. Stable atherosclerotic plaques contain few inflammatory cells and a small amount of Lp-PLA2. In contrast, unstable plaques most often do not have significant impact on arterial lumen but may be detected by its thin connective tissue cap, low collagen and high lipid content. A distinguishing factor between stable and unstable atherosclerotic plaque may also be the presence of activated inflammatory cells and increased Lp-PLA2 concentration in unstable plaque. These new insights indicate that Lp-PLA2 may be a risk factor, which is important for the formation of atherosclerotic plaque but also for its rupture. The purpose of applying markers of inflammation is to improve stratification of patients at risk, so that treatment intensity may be adjusted to the risk level. Lp-PLA2 inhibition is associated with decreased cytokines. Lipid-affecting drugs stabilize atherosclerotic plaque by reducing the central lipid core, decreasing macrophage infiltration, and thickening of the connective tissue cap. These drugs reduce Lp-PLA2 concentration and the frequency of cardiocerebrovascular events as well. Besides acting as a specific marker of atherosclerotic plaque inflammation, Lp-PLA2 has a significant prognostic value because of its direct role in the formation of rupture-prone atherosclerotic plaque, unlike classic risk factors, for example lipid measurement or vascular imaging, which do not directly estimate acute ischemic potential in the arterial wall. Studies have demonstrated correlation between increased Lp-PLA2 concentrations and enhanced risk of cardiocerebrovascular events, even after multivariate adjustment to classic risk factors. In addition to its high specificity for vascular inflammation, Lp-PLA2 concentration is stable in terms of time, unlike, for instance, CRP levels. Lp-PLA2 has been confirmed as an independent risk predictor, which is complementary to hsCRP. It could be used in clinical practice for improved risk assessment in patients with transient cardiocerebrovascular risk, particularly in those with metabolic syndrome (obese patients with mixed dyslipidemia, hyperglycemia, insulin resistance, and arterial hypertension). Lp-PLA2 levels allow for further risk stratification of high-risk patients into a very high risk group where more aggressive therapy is recommended, as well as the achievement of LDL-cholesterol levels < 2.5 or, even better, < 2.0 mmol/L as a feasible therapeutic target. Similar to hsCRP, the levels of Lp-PLA2 are reduced by lipid-affecting drugs, while its low concentrations are associated with a very low risk of cardiocerebrovascular events both in low- and high-risk population. According to recent American guidelines for assessing the risk of cardiovascular disease, Lp-PLA2 determination is recommended as an additional marker to the classic risk assessment in patients with moderate and high risk.

Donor heart selection and outcomes: An analysis of over 2,000 cases.

BACKGROUND: Decision-making when offered a donor heart for transplantation is complex, and supportive data describing outcomes according to acceptance or non-acceptance choices are sparse. Our aim was to analyze donor heart acceptance decisions and associated outcomes at a single center, and after subsequent acceptance elsewhere. METHODS: This investigation was a retrospective analysis of data obtained from the University of Vienna Medical Center and Eurotransplant centers for the period 2001 to 2015. RESULTS: Our center accepted 31.8% (699 of 2,199) of donor hearts offered. Unlike other centers, the acceptance rate, with or without transplantation, did not increase over time. Of the donor hearts rejected by our center, 38.1% (572 of 1,500) were later accepted elsewhere. Acceptance rates were twice as high for donor hearts initially rejected for non-quality reasons (339 of 601, 56.4%) compared with initial rejection for quality reasons (233 of 899, 25.9%). Three-year patient survival rate was 79% at Vienna; for donor hearts initially rejected by Vienna for non-quality reasons or quality reasons, it was 73% and 63%, respectively (p < 0.001). Outcomes at other centers after transplantation of grafts rejected by Vienna varied according to the reason for rejection, with good 3-year survival rates for rejection due to positive virology (77%), high catecholamines (68%), long ischemic time (71%), or low ejection fraction (68%), but poor survival was observed for hearts rejected for hypernatremia (46%), cardiac arrest (21%), or valve pathology (50%). CONCLUSIONS: A less restrictive policy for accepting donor hearts at our center, particularly regarding rejection for non-quality reasons or for positive virology, high catecholamine levels, longer ischemic time, or low ejection fraction, could expand our donor pool while maintaining good outcomes.

A case report of acute inferior myocardial infarction in a patient with severe hemophilia A after recombinant factor VIII infusion.

RATIONALE: The extent of protective effects of hemophilia against thrombotic events such as myocardial infarction (MI) and other acute coronary syndromes remains to be determined, as major risk factors for cardiovascular disease exist despite factor VIII (FVIII) deficiency. We present a case report of a 41-year-old male with severe hemophilia A and several cardiovascular risk factors. PATIENT CONCERNS: This morbidly obese patient developed chest pressure, followed by chest pain and difficulty in breathing shortly after receiving on-demand treatment with intravenous recombinant FVIII (rFVIII) (turoctocog alfa) dosed per body weight. DIAGNOSES: An electrocardiogram revealed a diagnosis of inferior ST-segment elevation MI. INTERVENTIONS: The patient underwent an urgent coronary angiography using a radial artery approach. During the next 12 months, he received dual antiplatelet treatment, acetylsalicylic acid 100 mg, and clopidogrel 75 mg daily. His treatment for severe hemophilia A was changed to plasma-derived FVIII replacement therapy. OUTCOMES: During this 12-month period, he experienced several small bleeds in his elbows. CONCLUSIONS: The temporal relationship between rFVIII infusion and onset of the MI suggests a possible association; however, apart from obesity, the patient also had other major risk factors for arterial thrombosis, such as hypertension and smoking. Furthermore, atherosclerotic disease and underlying atherosclerotic changes could not be excluded with certainty. This case highlights the importance of studies assessing the impact of excess body weight on rFVIII dosing.

Relation of atherosclerotic changes in retinal arteries to the extent of coronary artery disease.

The aim of this study was to explore the relation between atherosclerosis of the retinal arteries and the extent and severity of coronary artery disease (CAD). In 109 patients, aged 40 to 80 years, who underwent coronary angiography for suspected CAD, the degree of retinal arterial atherosclerosis (stages 1 to 4 according to Scheie) was determined. The fundus examination was done using direct ophthalmoscopy by an ophthalmologist blinded to the extent of the CAD. The CAD extent was evaluated by Gensini score, and coronary angiograms were analyzed by 2 expert observers who had no knowledge of the patients' retinal artery status. The extent and severity of retinal vessel atherosclerosis correlated strongly with the extent and severity of CAD. Thus, atherosclerotic changes in the retinal arteries may be a predictor of the extent of CAD.