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.

Patients with atrial fibrillation and mid-range ejection fraction differ in anticoagulation pattern, thrombotic and mortality risk independently of CHA2DS2-VASC score.

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.

Association between Circulatory and Plaque Resistin Levels with Carotid Plaque Instability and Ischemic Stroke Events.

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.

Takotsubo cardiomyopathy after the first electroconvulsive therapy regardless of adjuvant beta-blocker use: a case report and literature review.

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.

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.

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.

A pilot Croatian survey of risk factor (CRO-SURF) management in patients with cardiovascular disease.

A pilot survey was performed to determine the presence of known risk factors for cardiovascular disease in Croatian patients with diagnosed coronary heart disease (CHD) using a new questionnaire. The idea was to test this new and very simple questionnaire but also to compare the data collected in this pilot survey with the results of the last Croatian national survey (TASPIC-CRO V) and so to obtain the information whether secondary prevention has improved between 2003 and 2010. 122 patients with established CHD (88 men, 34 women, mean age 66.3 years) treated in Zagreb University Hospital Center were included. Data collection was based on filling the SURF questionnaire right after the clinical exam or later using review of medical records. Patients were hospitalized because of CABG (1%), PCI (8%), ACS (35%) or chronic stable angina (56%). The history of arterial hypertension had 95%patients (however, on admission mean systolic pressure was 130.1 mmHg, diastolic 76.8 mmHg), 90% had dyslipidaemia (total cholesterol <4.5 mmol/L had 43%; <4.0 mmol/L 33%; LDL-cholesterol <2.5 mmol/L 49%; <2.0 mmol/L 32%; HDL>1.2 mmol/L (women) or >1.0 mmol/L (men) had 67%), 25% had diabetes which was poorly regulated (mean HbA1c 8.2%), 18% were active smokers. After discharge only 24% performed cardiac rehabilitation. Mean body mass index of the patients was 28.3 kg/m2 (32% were obese, 72% overweight). Compared to TASPIC-CRO V there was lower usage of aspirin than recommended on discharge. This was also true for statin therapy. More patients were taking beta blockers, calcium antagonists and diuretics than 7 years ago. This pilot survey showed that CRO-SURF questionnaire is short, quick, effective and simple to use. It is a good and cost effective tool to collect data on CVD risk factors and their management. The results obtained by using it indicate that there is still a high prevalence of modifiable risk factors in Croatian patients with CHD.

Changes of recommended anticoagulation therapy in patients with atrial fibrillation and high thrombotic risk: long-term follow-up data from two hospital centers.

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.

Patients with higher body mass index treated with direct / novel oral anticoagulants (DOAC / NOAC) for atrial fibrillation experience worse clinical outcomes.

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 <30 kg/m2), class I obesity (71 with BMI 30-34.9 kg/m2) and class II + obesity (21 with BMI ≥35 kg/m2). RESULTS: Patients with higher BMI receiving DOACs were more likely to experience stroke/systemic embolism sooner (P = 0.043), experience major bleeding sooner (P < 0.001) and have shorter time to composite event consisting of thrombosis, bleeding or death (P < 0.001) whereas there was no significant association with overall survival (P = 0.470). BMI was significantly associated with thrombosis but not bleeding among dabigatran treated patients, and significantly associated with bleeding but not thrombosis among patients treated with factor Xa inhibitors. Associations of higher thrombotic, bleeding and composite endpoint risks with higher BMI remained statistically significant in multivariate Cox regression models adjusted for age, gender, eGFR, CHA2DS2VASC and HAS-BLED. CONCLUSION: Our findings indicate that obese patients receiving DOACs, especially ones with class II + obesity, might be under higher risks of stroke/bleeding depending on DOAC subtype. Loss of efficacy might be associated with dabigatran, whereas higher risk of major bleeding might be associated with factor Xa inhibitors.

Nonfatal cardiac perforation after central venous catheter insertion.

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.