Search

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., Transplant International, 36, ISSN:0934-0874, ISSN:1432-2277

Diabetes mellitus (DM) is related to higher rates of complications after coronary revascularization.1 The efficiency of drug-coated balloon (DCB) percutaneous coronary intervention (PCI) has been shown for in- stent restenosis (ISR) and native small-vessel disease, however data on outcomes in DM is scarce.2 The aim is to compare the incidence of target lesion restenosis at follow-up (FUP) coronary angiography in patients with and without DM receiving DCB PCI.

Atrial fibrillation (AF) patients with mid- range left ventricular ejection fraction (mrEF) of 40- 49% have neither preserved (pEF > 50%) nor reduced (rEF < 40%) EF and are increasingly being recognized as a distinct group with specific clinical risks. We aimed to retrospectively investigate clinical characteristics and associated thrombotic, bleeding and mortality risks of mrEF in comparison to pEF and rEF in a cohort of 1000 non-valvular AF patients presenting in our institution during the period 2013-2018. Patients with mrEF presented with older age (P < 0.001) and a higher frequency of arterial hypertension (P = 0.001) in comparison to both pEF and rEF patients. In comparison to pEF, mrEF patients were more likely to have diabetes mellitus (P = 0.004), lower HDL-cholesterol (P < 0.001) and lower estimated glomerular filtration rate (P < 0.001), significantly higher CHA2DS2- VASC score (P < 0.001), significantly higher HAS- BLED score (P = 0.002) and had a higher likelihood of receiving anticoagulant therapy, mostly warfarin (P = 0.001). In addition, mrEF patients had a significantly higher risk of thrombotic events (HR = 2.22 ; P = 0.015), death (HR = 1.71 ; P = 0.005) and composite endpoint of thrombosis, bleeding or death (HR = 1.65 ; P = 0.003) in comparison to pEF patients, but did not significantly differ in comparison to rEF patients. There was no significant difference regarding major bleeding risk. Associations with clinical outcomes remained statistically significant in multivariate models independently of CHA2DS2-VASC. Our findings support defining AF patients with mrEF as a subgroup with distinct clinical characteristics and increased risk for thrombotic events and death, irrespective of predetermined CHA2DS2- VASC risk. These patients seem to require special clinical considerations and more intensive control of cardiovascular risk factors.

Introduction: Due to fixed dosing of direct oral anticoagulants (DOACs), uncertainty exists about their efficacy in a population of obese/overweight patients. ----- Patients and methods: We retrospectively investigated a real-life cohort of 325 DOAC anticoagulated patients with atrial fibrillation [179 receiving dabigatran (55%), 74 apixaban (23%) and 72 rivaroxaban (22%)]. Patients were stratified according to the body mass index (BMI) into non-obese (233 with BMI

Aim : To investigate changes of anticoagulation therapy in patients with atrial fibrillation (AF) and high thrombotic risk.Methods : We retrospectively analyzed 1061 patients with non- valvular AF and indication for anticoagulation therapy referred in a period from 2013 to 2018 and followed-up for a median time of 38 months.Results : Therapy change occurred in 206 (19.5%) patients (195 switches and 11 permanent discontinuations). Only 37% of patients on warfarin had optimal dosing and their duration of therapy was significantly shorter compared to direct oral anticoagulants (DOACs ; (adjusted HR 1.21, 95% CI 1.09-1.37). Therapy change occurred in only 33% of patients with poorly controlled warfarin, and in only 24% of patients that experienced a thrombotic event while taking warfarin. Optimal dosing was an independent factor for any therapy change during follow-up, irrespective of type of anticoagulant drug at baseline. DOAC swapping occurred in 39% of all DOAC to DOAC switches, with one bleeding event and no thrombotic events documented after a DOAC swap.Conclusion : High risk patients with AF rarely discontinue anticoagulation therapy. The need for therapy change should be emphasized in patients with non-optimal dosing, and in patients that experience thrombotic events while taking warfarin.

Introduction: Data on heart transplant (HTx) patients and infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are very limited. There is significant heterogeneity in the clinical presentation. 1 Immunosuppression-related issues are of the main concern because of an increased risk for viral replication and superimposed infections. There is no evidence-based recommendation for the management of these patients. Some authors suggest modification in immunosuppression, i.e. discontinuation of mycophenolate mofetil (MMF) and calcineurin inhibitor (CNI) reduction in patients with more severe clinical presentation.2 Patients and Methods: This is a case series of 5 HTx recipients from our center who tested positive for COVID-19 infection and were treated in different COVID-19 specialized units. Results: There were 4 male and one female patients, 62-75 years old. Four of them were symptomatic and hospitalized, while one remained self-quarantined at home. The clinical presentation was mild to moderate, with symptoms including mild fever, dyspnea, and myalgia. X-ray signs of pneumonia were present in 3 patients, but none needed ICU care nor mechanical ventilation. Both a reduction of CNI dose with lower target serum concentration and MMF was discontinued in all patients. One patient was treated with hydroxychloroquine, one with remdesivir and one with steroid therapy. Antibiotics prophylaxis was administered in 2 patients. None of the patients experienced overt graft rejection and all patients have successfully recovered (Table 1). Conclusion: Lacking any evidence-based recommendation for the treatment of HTx patients infected with SARS-CoV-2, we are challenged to modify maintenance immunosuppression carefully balancing between the risk of uncontrolled viral replication with a superimposed infection on one side, and the increased risk of graft rejection on the other side. Further studies are needed to determine the optimal management of COVID-19 infection in these patients.

Background: Right ventricular (RV) failure is a common complication of left ventricular assist devic- es (LVAD).1, 2 We describe two cases of durable LVAD carriers requiring acute RV mechanical support provided using the ProtekDuo (LivaNova, IT) cannula, implanted via the right jugular internal vein, bypassing the RV by draining blood from the right atrium to an extracorporeal blood pump (Rotaflow pump, Maquet, DE) and returning it to the pulmonary artery (Figure 1). Case report 1: A 37-year-old male following LVAD implantation in 2016 due to dilated cardiomyopathy, was diagnosed with chronic RV failure in 2018. During a subsequent episode of of acute RV failure parenteral furosemide, dobutamine and intermittent levosimendan were started. Due to ensuing car- diogenic shock, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was placed. Three days later, an upgrade to a paracorporeal RVAD (p-RVAD) by placement of a ProtekDuo cannula and Ro- taflow pump providing a flow of 4.15 litres/minute was performed. An improvement of hemodynamic parameters was obtained with the p-RVAD, but while awaiting the high-urgent heart transplantation, multiorgan failure and repetitive infections ensued, leading to the patients’ death. Case report 2: In April 2020, a 28-year-old male earlier diagnosed with dilated cardiomyopathy was admitted for acute heart failure. Echocardiography showed a predominant left ventricular cardiomyo- pathy with significantly reduced LV ejection fraction of 15%. One week after admission, ventricular fibrillation occurred, terminated by implantable cardioverter-defibrillator. Due to hemodynamic compromise, dobutamine and norepinephrine were started, but VA-ECMO was required soon thereafter. Three days later, a durable LVAD (HeartMate 3, Abbott, USA) implantation was performed, however the patient was not weanable from cardiopulmonary by- pass due to acute RV failure, and promptly received a p-RVAD with the ProtekDuo cannula. Two weeks later, the p-RVAD was suc- cessfully weaned and he was discharged a month later and is currently in regular follow-up. Conclusion: We present two cases of acute and chronic RV failure in LVAD carriers. In both cases, the ProtekDuo cannula enabled acute RV support. Early institution of RV mechanical circulatory support, when needed, should improve patient outcomes.

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients during cardiac arrest and cardiogenic shock and is associated with increased survival rate1. Since mortality on ECMO is still rather high, SAVE (Survival after Veno-Arterial ECMO) score can be used to predict survival from refractory cardiogenic shock requiring ECMO2. Patients and Methods: We performed a retrospective analysis of 121 patients (78% male) who underwent VA-ECMO implantation in our Department from January 2011 till November 2020 (Figure 1 and Table 1). Results: Median age was 58 years with 21% of patients older then 65 years. Median of ECMO duration was 6 days. The most common causes of cardiogenic shock were acute myocardial infarction and cardiomyopathy (53% and 37%, respectively) (Figure 2), and 37% patients were implanted during cardiopulmonary resuscitation (eCPR). Overall survival on ECMO support was 59%, but in patients after CPR only 34%. Furthermore, of all patients, 34% were successfuly weaned and the rest who survived continued on advanced heart failure therapies (Figure 3), but overall survival in follow-up was only 26%. Median SAVE score was -8 with significantly less negative values in patients younger than 65 and treated after 2015. Also, patients treated before 2015 had significantly higher values of creatinine, free hemoglobine and international normalized ratio (INR) and their survival rate was only 39%, in comparison to those who were implanted after 2015 whose survival rate was 62%.Conclusion: Although results with ECMO support in cardiogenic shock in our Department improved throughout 10-years experience, they still exhibit high long-term mortality. Our observations reinforce the need for thorough assessment of each ECMO candidate, especially in respect to patient’s age, end-organ failure and SAVE score as key steps to ensure optimal outcomes.

Introduction: Congenital coronary artery fistulas (CAFs) are coronary artery anomaly characterized by a direct connection between one or more coronary arteries and any of the 4 chambers or any of the great vessels. The incidence is approximately 0.08-0.3% of patients undergoing coronary angiography. 1 Coronary angiography is the gold standard for detecting the presence of coronary artery fistulas and estimation of their hemodynamic significance. CAFs that drain into the LV may cause myocardial ischemia due to coronary steal syndrome but rarely lead to hemodynamic impairment, due to high pressure in the LV.2 Ageing increases the risk of their dilatation, thereby increasing the risk of complications. Case report: 72-year-old female with a history of arterial hypertension, dyslipidemia, and chronic obstructive pulmonary disease was hospitalized for anginal symptoms. She reported anginal symptoms during minimal physical activity and relieved by nitroglycerine. Echocardiography showed preserved systolic function with a discrete hypocontractility of the apical segment of the anterolateral and anterior wall. Coronary angiography showed coronary arteries without angiographically significant stenosis. However, intensive opacification of myocardial walls after contrast injection and contrast drainage into the ventricles through extensive multiple microfistulas were observed. Due to multiple and smallsized CAFs our patient was not suitable for interventional or surgical closure. The antianginal therapy was upgraded with trimetazidine (2x35 mg) and ranolazine (2x500 mg) with favorable response. Conclusion: Although a rare cause of angina pectoris, the coronary steal syndrome caused by the coronary arterial-ventricular fistulas should be considered during diagnostic work-up. Besides myocardial ischemia, CAFs may cause arrhythmias, heart failure, and infective endocarditis.

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in refractory cardiogenic shock and cardiac arrest but is characterized by increased left ventricular (LV) afterload and consequent development of pulmonary oedema (ECMO lungs). The ProtekSoloTM (LivaNova, IT) cannula is inserted via the right femoral vein to the left atrium, by a trans-septal puncture (under the guidance of transesophageal echocardiography and fluoroscopy). This bypasses the LV by draining blood from the left atrium to a paracorporeal pump (eg Rotaflow pump (Maquet, DE)) and returning it via a femoral artery cannula, thus providing direct unloading of LV.1-3 We aimed to demonstrate our experience with the paracorporeal LV assist device using the ProtekSolo cannula and Rotaflow pump (PSp-LVAD). Patients and Methods: 7 adult patients underwent PSp-LVAD placement in UHC Zagreb from January to December 2020. We divided the patients in two groups: those who required PSp-LVAD to treat ECMO lungs (n=4) and those who received PSp-LVAD implantation prior to developing ECMO lungs (n=3). In addition to the description of the treated patients, we also assessed 30-day all-cause mortality. Results: The baseline characteristics of patients are shown in Table 1. All patients were male, mean age 56±9.3 years. 57.1% of patients underwent PSp-LVAD placement due to worsening of chronic heart failure and 42.9% due to acute coronary syndrome. Concurrent infection was present in 57.1% of patients. 71.4% were first on VA-ECMO support, of those 80% developed ECMO lungs. Laboratory tests (Figure 1) show improvement in kidney and liver function after PSp-LVAD placement. Outcomes are shown in Table 2 ; patients in prophylactic group have lower observed 30-day mortality rate (33% vs 75%) and longer VA-ECMO support duration due to lower mortality. Besides 2 patients who are still in active treatment, all others died during initial hospitalization due to infective complications, predominantly those that had a concurrent infection upon institution of the PSp-LVAD. Conclusion: Pulmonary edema (ECMO lungs) due to increased LV afterload is a major complication of VA-ECMO. Prophylactic LV unloading by PSp-LVAD seems associated with lower 30-days mortality.

Background: Current guidelines recommend genetic counselling and testing in patients with familial non-ischemic idiopathic cardiomyopathies with hypertrophic, dilated, restrictive or arrhythmogenic phenotype.1, 2 We aimed to investigate genotype features of patients with non-ischemic cardiomyopathies in advanced stage of heart failure in University Hospital Centre Zagreb. Methods: Genetic testing (single variant and multiple variant testing) was performed in part using the in-house genetics laboratory, and also in a collaborating genetics laboratory in Helsinki, Finland (Blueprint Genetics). Pathogenic and likely pathogenic variants that established a molecular diagnosis were confirmed by Sanger sequencing. Results: From September 2016 to December 2020, we have performed genetic testing in 66 patients. Of this number, 14 patients (8 males, 41.5±14.3 years) had advanced heart failure as evidenced by either having undergone heart transplantation, mechanical circulatory support implantation, or were currently listed for heart transplantation. Before genetic testing, clinically observed phenotypes indicated dilated cardiomyopathy in 6 patients, restrictive cardiomyopathy in 6 patients, and arrhythmogenic cardiomyopathy in 2 patients. Diagnostic yield of the performed genetic tests was relatively high, only one test did not identify any mutations, and 4/14 identified mutations that can currently be classified only as variants of uncertain significance. Pathogenic and likely pathogenic mutations predominantly affected genes coding proteins of the sarcomere, cellular and nuclear membrane, or pathologic protein such as transthyretin (Table 1). Genetic testing lead to change in the clinically determined diagnosis in 4/14 patients. Results of genetic testing in this group of patients warranted further family clinical screening in all of the patients, and family genetic screening in 5 eligible patients. Conclusion: Genetic testing in our advanced heart failure population yields important information on etiology of the diseases, and indicates further family screening.

Smaller stent diameter represents risk factor for target lesion failure (TLF). Drug coated balloons (DCB) could represent valid substitution for stents in selected patients.The aim of the study was to assess clinical and angiographic outcomes after percutaneous coronary interventions (PCI) using DBC in treatment of coronary arteries ≤ 2.5 mm.

Atrial fibrillation (AF) patients with mid-range left ventricular ejection fraction (mrEF) of 40-49% have neither preserved (pEF 50%) nor reduced (rEF 40%) EF and are increasingly being recognized as a distinct group with specific clinical risks. We aimed to retrospectively investigate clinical characteristics and associated thrombotic, bleeding and mortality risks of mrEF in comparison to pEF and rEF in a cohort of 1000 non-valvular AF patients presenting in our institution during the period 2013-2018. Patients with mrEF presented with older age (P 0.001) and a higher frequency of arterial hypertension (P = 0.001) in comparison to both pEF and rEF patients. In comparison to pEF, mrEF patients were more likely to have diabetes mellitus (P = 0.004), lower HDL-cholesterol (P 0.001) and lower estimated glomerular filtration rate (P 0.001), significantly higher CHA

Aim: Aim of the study was to compare angiographic and clinical outcomes after percutaneous coronary interventions (PCI) using drug coated balloons (DCB) between patients treated for “de novo” lesions and in-stent restenosis (ISR) in acute coronary syndrome (ACS). Patients and Methods: Study included 128 ASC patients treated with DCB between 2012 and 2019. All coronary angiographies were reviewed to determine indication, lesion complexity, vessel size and procedural success. Baseline and follow up clinical data were extracted from hospital digital database. Results: Mean patient age was 63.8 years, with the majority being men (75.8%, N=97). In total, 24 (18.8%) patients were treated for ISR. Comparison of clinical, angiographic and procedural characteristics between groups is presented in Table 1. Patients in the non-ISR group had more often multivessel disease (56.7 vs 25.0%, p=0.005), bifurcation PCI (45.0 vs 20.8%, p=0.042) and more DCB used in the index event (1.1±0.3 vs 1.0±0, p=0.004). Furthermore, they had more concomitant PCI with stent implantation in other lesions (75.9 vs 33.3%, p

Introduction: Cardiac allograft vasculopathy (CAV) is a common cause of late graft failure and mortality in heart transplant recipients. Concentric intimal proliferation that reflects immune-mediated vascular damage in the early post-transplant years is difficult to recognize by conventional coronary angiography. Optical coherence tomography (OCT) is a high resolution intravascular imaging technique that has the potential to identify subtle early vessel wall changes and shape the therapeutic approach that may improve patients’ outcomes. Case report: 68-year-old male patient underwent heart transplantation with positive lymphocyte crossmatch and Luminex that detected anti-HLA class I (A1, A25, B8, B57) donor-specific antibodies with MFI up to 2500. The patient was treated with steroid, antilymphocyte (rATG) induction, tacrolimus, and mycophenolate mofetil, in combination with IVIG and plasmapheresis. Graft function was preserved, biopsies showed no or mild cellular-mediated rejection (1R) with no signs of antibody-mediated rejection (AMR) with negativization of anti-A1 and -A25 antibodies. However, control biopsy after 6 months became positive for AMR. The patient was treated with steroid pulse, IVIG, plasmapheresis, and rituximab. The following biopsies were negative for AMR and the patient remained with preserved graft function. One year after transplantation we performed control coronary angiography with OCT. While coronary angiography was interpreted as normal, control OCT showed significant diffuse intimal thickening with maximal intimal thickness up to 920 μm and intima/media cross-sectional media of ≥1 (Figure 1). This finding prompted a change in therapy with the maximization of statin dose and introduction of everolimus in the maintenance immunosuppressive regimen. Conclusion: This case report indicates the limitation of conventional coronary angiography in the early detection of transplant vasculopathy. OCT is able to establish the diagnosis and trigger specific therapeutic interventions like the introduction of everolimus before vascular changes become visible on conventional coronary angiography and resistant to treatment. Unfortunately, we still lack clearly defined OCT criteria for both diagnosis and treatment, but the progress in this field of transplant cardiology is promising.

Cardiac tamponade caused by perforation of the cardiac wall is a rare complication related to central venous catheter (CVC) placement. A 71- year-old female with a previous history of moderate aortic stenosis and kidney transplantation was admitted to hospital due to global heart failure and worsening of allograft function. Intensified hemodialysis was commenced through a CVC placed in the right subclavian vein. Chest radiography revealed catheter tip in the right atrium and no signs of pneumothorax. Thorough diagnostics outruled immediate life- threatening conditions, such as myocardial infarction and pulmonary embolism. However, not previously seen, 2 cm thick pericardial effusion without repercussion on the blood flow was visualized during echocardiography, predominantly reclining the free surface of the right atrium, with fibrin scar tissue covering the epicardium - it was the spot of spontaneously recovered cardiac wall perforation. Follow-up echocardiogram performed before the discharge showed regression of the previously found pericardial effusion.

Introduction: Targeted temperature management (TTM) is recommended in the European Resuscitation Council Guidelines for Post-resuscitation Care.1 However, previous studies report controversial results on the effect of TTM on platelet function (PF) in patients on dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors. Hypothesis: To assess if the effect of DAPT on platelet inhibition in patients undergoing TTM for out-of-hospital cardiac arrest (OHCA) is reduced compared to patients on the same therapy not undergoing this procedure. Patients and Methods: Clinical characteristics and PF were analyzed in 56 consecutive patients admitted to the Department of Cardiology at the University Hospital Centre between January 2012 and January 2019 under the diagnosis of acute myocardial infarction (AMI). Out of these 56 patients, 17 underwent TTM to 34°C (Intervention group) while the other 39 did not (Control group). Both groups received the loading dose of DAPT. We analyzed residual PF using the Multiplate® PF analyzer ADP test. Platelet function tests (PFT) were performed 18-24 hours after therapy initiation in both groups and 18-24 hours after return to normal body temperature of 36.5° C in the TTM group. The control group had an average temperature of 36.5° C at the time of the PFT. Results: There were 39 patients with a mean (SD) age of 63.2 (9.9) years in the Control group and 17 patients with a mean (SD) age of 58.6 (8.2) in the Interventional group. There were no significant differences in the baseline parameters between the groups (history of IHD, hyperlipidemia, diabetes mellitus, smoking, gender, prior medical therapy, current medical therapy). At the first time point (18-24 hours after initiating therapy) the intervention group had a significantly higher residual PF when compared to the control group (31.5 U vs 17.9 U; p

Background: A new hemodynamic environment is set up after heart transplantation (HTx).1, 2 Our aim was to assess changes in diastolic function of the left (LV) and right (RV) ventricle in HTx patients (Pts) during the 1st year and the influence of donor age, graft ischemic time (GIT) and acute right ventricular failure (ARVF). Patients and Methods: In 55 “healthy” HTx Pts echo was performed 1- and 12 months after HTx. Data on mitral valve (MV) E- (Ew) and A-wave velocity (Aw), MV and tricuspid (TV) E/A ratio, MV and TV E’ and A’ by tissue Doppler, septal E/E’, pulmonary vein diastolic velocity (PVd), systolic pulmonary pressure (sPAP), left atrial indexed volume (LAVI), right atrial pressure (RAP) were collected. Results: Ew significantly decreases during the 1st year (0.80 vs. 0.73 m/s ; p=0.036) as well as E/E’ (11.5 vs. 9.1 ; p=0.009), PVd (0.67 vs. 0.55 m/s ; p mean of 41 years) caused initially lower MV-E’ (r=-0.390, p=0.010) and higher sPAP (r=0.285 ; p=0.045). GIT had no influence on diastolic parameters. ARVF significantly correlated with lower TV-A’ acutely and after 1 year (ARVF 5 vs. no-ARVF 8 cm/s ; r=-0.600, p= 0.011) and higher RAP (r=0.414, p=0.003). Conclusion: During the 1st postransplant year there is improvement in LA diastolic function with better early passive LV filling and reduction in PAH, without change in active filling phase or LA volume. In Pts with significant PAH mean E/E’ ratio within 1st month was 14, but after a year in Pts with persistent PAH it declines to only 10, preserving the higher E/A ratio. Higher donor age could impair the early LV ventricular filling with a trend toward more PAH but MV-E’ improves with time. ARVF reduces active RV filling (TV-A’) throughout the 1st year. GIT does not have influence on diastole.

Background: Decrease in platelet count following the induction with polyclonal anti-thymocyte globulin (ATG) is deemed as an adverse event, while decrease in lymphocyte count represents a therapeutic goal1. Still, the effect on platelets may represent an important part of ATG anti-rejection mechanisms. Patients and Methods: This was a retrospective single-center study of consecutive HTx (heart transplantation) patients (pts) from February 2010 to February 2018 in University Hospital Centre Zagreb. All pts received rATG (Thymoglobulin®) 1.5 mg/kg daily during the first 5 days. Complete blood count with differential was assessed on days 0, 7 and 14 after HTx. The incidence of cellular-mediated rejection (ACR) was monitored for two years after HTx. ACR was classified according to ISHLT classification from 1990 and expressed as ACR of grade 1B or higher (≥1B). Results: A total of 159 pts were transplanted. Median age was 55 years (IQR, 47-62 years), 76% were male. A total of 27 pts (17 %) experienced ACR ≥1B during 24 months. Pts with ACR of grade ≥1B had higher platelet count on day 7 (145 vs 104 x 103/μL, p

Background: Decrease in platelet count following the induction with polyclonal anti-thymocyte globu- lin (ATG) is deemed as an adverse event, while decrease in lymphocyte count represents a therapeutic goal1. Still, the effect on platelets may represent an important part of ATG anti- rejection mechanisms. Patients and Methods: This was a retrospective single-center study of consecutive HTx (heart trans- plantation) patients (pts) from February 2010 to February 2018 in University Hospital Centre Zagreb. All pts received rATG (Thymoglobulin®) 1.5 mg/kg daily during the first 5 days. Complete blood count with differential was assessed on days 0, 7 and 14 after HTx. The incidence of cellular-mediated rejection (ACR) was monitored for two years after HTx. ACR was classified according to ISHLT classification from 1990 and expressed as ACR of grade 1B or higher (≥1B). Results: A total of 159 pts were transplanted. Median age was 55 years (IQR, 47-62 years), 76% were male. A total of 27 pts (17 %) experi- enced ACR ≥1B during 24 months. Pts with ACR of grade ≥1B had higher platelet count on day 7 (145 vs 104 x 103/μL, p

Introduction: Dual antiplatelet therapy (DAPT) represents one of the pillars in the treatment of acute coronary syndromes (ACS)1. In the past the most commonly used combination of antiplatelet drugs has been acetylsalicylic acid (ASA) and clopidogrel. Clopidogrel had a high incidence rate of high residual platelet reactivity and has, in recent years, been replaced with ticagrelor, a more potent platelet inhibitor with a more uniformed response across the patient population. The effect of high dose atorvastatin on platelet reactivity mediated by ASA and clopidogrel is well researched, however no studies have been published analyzing this effect when clopidogrel is substituted with ticagrelor. Purpose: To investigate if high dose atorvastatin modifies PF mediated by DAPT in patient with ACS as measured by platelet function tests (PFTs). Patients and Methods: We analyzed clinical characteristics and PF in patients presenting with ACS at the Department of Cardiovascular Diseases at the University Hospital Centre Zagreb from December 2015 to February 2018. Primary endpoint was PF after treatment with DAPT and/or high dose atorvastatin. We analyzed PF using the Multiplate platelet function analyzer. PFTs were performed 18-24 hours after therapy initiation. None of the patients were taking statins before the index event. Results: There were 35 patients with a mean (SD) age of 61.6 (12.2) years in the atorvastatin group and 29 patients with a mean (SD) of 62.6 (9.6) years in the no-atorvastatin group. Both groups were identical in all the baseline parameters except history of hyperlipidemia (34.5% vs 65.7%, P=0.023). There were no significant differences between the two groups in PF analyzed with PFTs (Figure 1). The difference in residual platelet reactivity remained non-significant even after adjusting for sex, age and hyperlipidemia as the only co-variate that was significantly different between the group (P=0.432). Conclusion: In this pilot study on a limited sample we found no difference in residual PF in patients on DAPT weather they are on treatment with high dose atorvastatin or not. These results show that the pleiotropic effects of atorvastatin on platelet reactivity are not significant in patients taking DAPT with ticagrelor and ASA. Acknowledgement: This pilot study was funded by Croatian Science Foundation.

Background: The number of transplant patients of childbearing age has increased. Decisions regarding the pregnancy management are challenging. Close monitoring includes screening for complications including rejection, graft dysfunction, and infection. First pregnancy in a post-cardiac transplant patient was reported in 1988 in a female patient who conceived less than 2 years post-transplant. Since then, there are many case reports that have demonstrated successful pregnancies in solid organ transplant recipients.1-3 Case report: We present a case of 42-years-old female patient who underwent heart transplant 2016. In 2018 the patient expressed wishes for pregnancy and childbirth. A multidisciplinary team of cardiologists and gynecologists was formed and preconception and genetic counseling given. Before pregnancy we adjusted standard immunosuppressant therapy – mycophenolate mofetil was excluded, prednisone was continued in dose of 5 mg daily, and tacrolimus titrated to achieve concentration of 10-15 ng/ml. One month later, myocardial biopsy excluded graft rejection and 6 months later patient conceived naturally. Graft function was assessed by regular monthly NT-proBNP check. Echocardiography performed at 4th and 35th week of pregnancy showed normal graft function. In 36th week of pregnancy patient was admitted to our Department due to renal failure and hyperkalemia and was treated conservatively. Due to labor contractions on the 7th day of hospitalization, urgent caesarean section was performed in general anesthesia. Our patient gave birth to a healthy male newborn, without postpartal complications. Standard immunosuppressant therapy with mycophenolate mofetil, tacrolimus and prednisone was introduced immediately after birth. Repeated myocardial biopsy performed in the follow-up showed no signs of graft rejection. Conclusion: Pregnancy and childbirth in post-cardiac transplant patient is feasible and should be managed by multidisciplinary team of healthcare providers.

Takotsubo cardiomyopathy (TC) is a rare complication of electroconvulsive therapy (ECT), an effective and safe treatment for severe cases of depression and psychosis. There are reports on 16 patients who developed TC after ECT, and these were predominantly female patients treated with antidepressants for depressive disorder. We describe a case of a 40-year-old male patient, with a history of schizophrenia and heavy caffeine and nicotine use, treated for acute psychotic episode with haloperidol and clozapine. Propranolol was administered because of clozapine-induced tachycardia. After 8 weeks without therapeutic response, the patient was referred for standard ECT procedure, which included premedication and bifrontotemporal stimulation. Two hours later, the patient experienced gastric pain and had increased troponin and natriuretic peptide levels and ST-elevation. After inotrope and anticoagulant treatment and replacement of antipsychotics, the patient remained stable. Contrary to common opinion, previous adrenergic blockade in this patient did not prevent TC occurrence. TC pathophysiology remains unclear although it has been related to the burst of norepinephrine neurons. Psychosis has also been associated with catecholamine dysfunction, and excessive psychological stress with long-term norepinephrine dysfunction. Animal models have shown that ECT, clozapine, and nicotine and caffeine use could considerably increase catecholamine levels. Clinical understanding of rare cardiac ECT complications could improve early recognition of patients at risk for TC and ensure safe ECT protocols.

ses of ischemic stroke. The risk of ischemic stroke increases with the degree of carotid stenosis and plaque vulnerability. The aim of this study was to investigate the association of circulating and plaque resistin levels with plaque vulnerability and ischemic stroke events in patients with moderate- to high-grade carotid artery stenosis. Methods: 40 patients with ischemic stroke events and 38 neurologically asymptomatic patients scheduled for carotid endarterectomy were recruited for this study. Fasting blood samples for laboratory analysis were collected preoperatively and serum resistin levels were measured by enzyme-linked immunosorbent assays. Carotid endarterectomy specimens were analyzed according to the gold-standard procedure of histological classification. Plaque resistin expression was determined by standard immunohistochemical procedure. Results: Serum resistin levels and resistin plaque expression were found to be significantly higher in subjects with unstable carotid plaque (P < .001) while significantly higher serum resistin levels were also present in patients with ischemic stroke events (P < .001). In univariate stepwise logistic regression analysis, higher serum resistin levels were significantly associated with plaque instability (OR 2.223, 95% CI 1.488-3.320, P < .0001) and ischemic stroke events (OR 1.237, 95% CI 1.079-1.420, P = .002). There was also a significant association between higher serum and plaque resistin expression (OR 1.663, 95% CI1.332-2.077, P < .0001). These associations remained significant in all models of multivariate logistic regression analysis. High serum and plaque resistin levels were also significantly associated with specific histological features of plaque instability. Conclusion: The results suggests that serum resistin levels may be used as a potential biomarker of plaque vulnerability and ischemic stroke events in patients with moderate- to high-grade carotid artery stenosis and highlight the possible relationship that plaque resistin expression has with histological features of plaque vulnerability.

Introduction: Pulmonary vein isolation (PVI) procedures increase the potential thromboembolic risk.1The aim of this study was to compare the effect of radiofrequency (RF) ablation and cryoablation on platelet reactivity (PR) in patients with atrial fibrillation (AF). Patients and Methods: We analyzed PR levels using Multiplate function analyzer in 63 consecutive pa-tients undergoing PVI procedures in our institution. Blood samples were drawn just before the proce-dure and on the following day. Fourty six (46) and seventeen (17) patients underwent cryoablation and RF ablation, respectively. There was no difference in demographics and baseline platelet parameters (platelet count, MPV and PR) between patients in RF and cryo group. ASPI, ADP and TRAPtest were used to --assess multiple pathways of platelet activation. Results: One day after the procedure mean PR droped from baseline levels in both study groups. The observed delta was more expressed in the cryo group for all three PR tests but only ADPtest showed statistically significant difference in PR. Conclusion: Our results show that PR after cryoablation is less pronounced compared to RF procedure. This affirms that thrombogenic burden of PVI is lower with cryoablation. We hypothesize that this could be a result of endocardial integrity preservation and decreased availability of platelet agonists during cryoablation. These results warrant further investigations with periinterventional PR meas-urements on a larger cohort of patients

Introduction: Benefits of venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory failure (RF) have been identified in different trials1. Due to surfactant washout, drowning often results in acute respiratory distress syndrome (ARDS), which remains the most important cause of death in those patients surviving the transfer to hospital. Case report: 32-year-old male patient with no prior medical history presented to our Emergency Department following drowning and a successful resuscitation. He was found submerged in the pool just a couple of minutes after being seen conscious and swimming. Lifeguard on duty pulled him out of the pool and started cardiopulmonary resuscitation. Upon the arrival of Emergency Medical Service, patient had a pulse and was breathing spontaneously, but was exhibiting grand mal seizures and not recovering consciousness. In the emergency department he was put on mechanical ventilation (MV) due to global RF and in the Coronary Care Unit therapeutic hypothermia (TH) was started. Urgent diagnostics was performed and no signs of stroke, coronary artery disease, pulmonary embolism or significant electrolyte imbalance were detected. 12-lead ECG and echocardiography showed no abnormal findings despite severe respiratory acidosis. Due to signs of ARDS (Figure 1) and worsening RF in spite of increasing MV support, VV ECMO implantation was indicated. It was successfully conducted in the early period (