Comparison of apixaban versus aspirin for the prevention of latent bioprosthetic aortic valve thrombosis: study protocol for a prospective randomized trial.

BACKGROUND: The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. METHODS: In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. DISCUSSION: Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. TRIAL REGISTRATION: ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.

Efficacy and Safety of High PEEP NIV in COVID-19 Patients.

OBJECTIVE: To investigate the efficacy and safety of non-invasive ventilation (NIV) with high PEEP levels application in patients with COVID-19-related acute respiratory distress syndrome (ARDS). METHODS: This is a retrospective cohort study with data collected from 95 patients who were administered NIV as part of their treatment in the COVID-19 intensive care unit (ICU) at University Hospital Centre Zagreb between October 2021 and February 2022. The definite outcome was NIV failure. RESULTS: High PEEP NIV was applied in all 95 patients; 54 (56.84%) patients could be kept solely on NIV, while 41 (43.16%) patients required intubation. ICU mortality of patients solely on NIV was 3.70%, while total ICU mortality was 35.79%. The most significant difference in the dynamic of respiratory parameters between 2 patient groups was visible on Day 3 of ICU stay: By that day, patients kept solely on NIV required significantly lower PEEP levels and had better improvement in PaO2, P/F ratio, and HACOR score. CONCLUSION: High PEEP applied by NIV was a safe option for the initial respiratory treatment of all patients, despite the severity of ARDS. For some patients, it was also shown to be the only necessary form of oxygen supplementation.

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.

Sequential Extracorporeal Blood Purification Is Associated with Prolonged Survival among ICU Patients with COVID-19 and Confirmed Bacterial Superinfection.

INTRODUCTION: This study investigates the impact of sequential extracorporeal treatments with oXiris® or CytoSorb® plus Seraph-100® on the clinical and laboratory parameters of critically ill COVID-19 patients with bacterial superinfection. METHODS: Patients admitted to the intensive care unit with COVID-19, bacterial superinfection, and undergoing blood purification (BP) were enrolled in this prospective, single-center, observational study. "standard BP" with oXiris® or CytoSorb® were used in 35 COVID-19 patients with bacterial infection. Seraph-100® was added in 33 patients when available serially in the same oXiris® circuit or as sequential treatment with CytoSorb® as a sequential BP. RESULTS: A significant reduction in SOFA score 3 days after treatment was observed in patients undergoing sequential BP (11.3 vs. 8.17, p < 0.01) compared to those undergoing "standard BP" (11.0 vs. 10.3, p > 0.05). The difference between the observed and expected mortality rate based on APACHE IV was greater in the sequential BP group (42.4% vs. 81.7%, p < 0.001) than the "standard BP" (74.2% vs. 81.7%, p > 0.05). Patients treated with sequential BP had a longer survival than those treated with "standard BP" (22.4 vs. 18.7 months; p < 0.001). CONCLUSIONS: The sequential approach may enhance the positive effect of BP on organ dysfunction among critically ill patients with COVID-19 and bacterial superinfection.

Veno-Arterial Extracorporeal Membrane Oxygenation as a Bridge to Heart Transplant-Change of Paradigm.

Despite advances in medical therapy and mechanical circulatory support (MCS), heart transplant (HT) remains the gold standard therapy for end-stage heart failure. Patients in cardiogenic shock require prompt intervention to reverse hypoperfusion and end-organ damage. When medical therapy becomes insufficient, MCS should be considered. Historically, it has been reported that critically ill patients bridged with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) directly to HT have worse outcomes. However, when the heart allocation system gives the highest priority to patients on VA-ECMO support, those patients have a higher incidence of HT and a lower incidence of death or removal from the transplant list. Moreover, patients with a short waiting time on VA-ECMO have a similar hazard of mortality to non-ECMO patients. According to the reported data, bridging with VA-ECMO directly to HT may be a solution in the selection of critically ill patients when the anticipated waiting list time is short. However, when a prolonged waiting time is expected, more durable MCS should be considered. Regardless of the favorable results of the direct bridging to HT with ECMO in selected patients, the superiority of this strategy compared to the bridge-to-bridge strategy (ECMO to durable MCS) has not been established and further studies are mandatory in order to clarify this issue.

Impact of progressive aortic regurgitation on outcomes after left ventricular assist device implantation.

Aortic regurgitation (AR) following continuous flow left ventricular assist device implantation (cf-LVAD) may adversely impact outcomes. We aimed to assess the incidence and impact of progressive AR after cf-LVAD on prognosis, biomarkers, functional capacity and echocardiographic findings. In an analysis of the PCHF-VAD database encompassing 12 European heart failure centers, patients were dichotomized according to the progression of AR following LVAD implantation. Patients with de-novo AR or AR progression (AR_1) were compared to patients without worsening AR (AR_0). Among 396 patients (mean age 53 ± 12 years, 82% male), 153 (39%) experienced progression of AR over a median of 1.4 years on LVAD support. Before LVAD implantation, AR_1 patients were less frequently diabetic, had lower body mass indices and higher baseline NT-proBNP values. Progressive AR did not adversely impact mortality (26% in both groups, HR 0.91 [95% CI 0.61-1.36]; P = 0.65). No intergroup variability was observed in NT-proBNP values and 6-minute walk test results at index hospitalization discharge and at 6-month follow-up. However, AR_1 patients were more likely to remain in NYHA class III and had worse right ventricular function at 6-month follow-up. Lack of aortic valve opening was related to de-novo or worsening AR (P < 0.001), irrespective of systolic blood pressure (P = 0.67). Patients commonly experience de-novo or worsening AR when exposed to continuous flow of contemporary LVADs. While reducing effective forward flow, worsening AR did not influence survival. However, less complete functional recovery and worse RV performance among AR_1 patients were observed. Lack of aortic valve opening was associated with progressive AR.

Heart failure in adults with congenital heart disease.

Heart failure (HF) represents the leading cause of morbidity and mortality in adult patients with congenital heart disease. The nature of underlying congenital heart disease has bearing on timing and severity of HF and impacts on short- and long-term outcomes. HF can be subclinical, underscoring the need for close follow-up at tertiary centres with timely management of target hemodynamic lesions. Drug therapies have an effect in systemic left ventricle failure and are employed in acute HF for symptomatic relief. Data on elective drug therapy for the failing systemic right ventricle and/or Fontan circulation is currently lacking. Drugs such as angiotensin receptor blockers with neprilysin inhibitors or sodium-glucose co-transporter-2 inhibitors may show benefit. Cardiac resynchronization therapy, in appropriately selected patients, is considered a treatment option. Mechanical circulatory support and transplantation remain the last resource in highly selected patients. As the congenital heart disease population continues to grow and age, both outpatient and inpatient service for HF will continue to play a major role in the care of adult patients with congenital heart disease.

De Novo Aortic Regurgitation After Continuous-Flow Left Ventricular Assist Device Implantation.

Continuous-flow left ventricular assist devices (cf-LVAD) play an important role in the management of patients with advanced heart failure. De novo aortic regurgitation after cf-LVAD implantation may adversely impact device performance. We performed a systematic search of PubMed, SCOPUS, and Cochrane Library for articles reporting on the incidence and predictors of de novo aortic regurgitation among cf-LVAD recipients. Eight studies totaling 548 patients were identified in the meta-analysis. The pooled incidence of de novo AR across the analyzed studies was 37%. Factors influencing its development and progression are older age, persistent aortic valve closure, being female, and duration of cf-LVAD support.

Manual Intracardiac Electrogram Method Is Accurate Alternative to Echocardiography for Atrioventricular and Interventricular Optimization in Cardiac Resynchronization Therapy.

Some manufacturers do not provide automated intracardiac electrogram method (IEGM) systems for atrioventricular (AV) and interventricular (VV) delay optimization in cardiac resynchronization therapy (CRT). We aimed to evaluate the accuracy of manual IEGM method in 48 patients previously implanted with Medtronic Syncra CRT. All patients underwent standard device interrogation followed by CRT optimization by IEGM method and by echocardiography one month after implantation. The patient mean age was 60.7±11.8 years and there were 33 (68.8%) males. After CRT implantation, the left ventricular ejection fraction increased from 28.0±7.9% to 39.1±11.0% (p<0.001). Optimal aortic flow Velocity Time Integral (aVTI) was obtained when VV was set to 20-50 ms left ventricular pre-activation. There was a strong correlation between VV values determined by echocardiography and IEGM (R=0.823, p<0.001). We found no significant difference in AV, VV and aVTI values between echocardiography and IEGM method. However, IEGM was significantly less time-consuming than echocardiography [20 (10-28) vs. 40 (35-60) minutes, p<0.001]. Manual IEGM method may be good alternative to echocardiography and automated IEGM method. It also emphasizes the need for implementation of automated IEGM systems in as many CRT devices as possible.

Quantification of myocardial extracellular volume fraction with cardiac MR imaging for early detection of left ventricle involvement in systemic sclerosis.

PURPOSE: To determine whether extracellular volume fraction (ECV) quantification at cardiac magnetic resonance (MR) imaging can demonstrate subclinical left ventricle (LV) abnormalities in a cohort of consecutive systemic sclerosis (SS) patients, and to investigate the relationship between ECV and diastolic and systolic LV function. MATERIALS AND METHODS: All subjects gave their written informed consent. The protocol was approved by the ethics committee. ECV quantification with cardiac MR imaging was prospectively performed in 33 consecutive SS patients with normal echocardiography results and no late gadolinium chelate enhancement at MR imaging. Left ventricular and atrial volumes and peak circumferential strain were measured at cardiac MR imaging. Diastolic function was assessed at echocardiography. The results were compared with those of 16 age-matched healthy control subjects by using Mann-Whitney and Kruskal-Wallis tests. RESULTS: SS patients had significantly higher global ECV (P < .001) and higher local ECV for all basal and midventricular LV segments. Global ECV significantly correlated with left atrial volume (P = .002) and with the grade of diastolic dysfunction (P = .016). The majority of SS patients (63%; 21 of 33 patients) had a high global ECV and a low global systolic circumferential strain. CONCLUSION: ECV quantification can identify LV abnormalities at an early stage in SS patients. These abnormalities may reflect increase in diffuse myocardial fibrosis and are associated with diastolic LV dysfunction.

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.

Initial patency of the infarct-related artery in patients with acute ST elevation myocardial infarction is related to platelet response to aspirin.

INTRODUCTION: A proportion of patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary angiography (PCI) presents with patent infarct-related artery (IRA) on initial angiography. We tested the hypothesis that stronger platelet response to aspirin in these patients at admission might be associated with higher initial coronary flow in the IRA. METHODS: Platelet response to aspirin was assessed with Multiplate ASPI-test before coronary angiography in 70 patients on previous aspirin treatment admitted for acute STEMI. Coronary flow on initial angiogram was evaluated quantitatively according to the Thrombolysis in Myocardial Infarction (TIMI) grading system. Depending on the degree of arachidonic acid (AA) induced platelet aggregation in ASPI-test, patients were stratified into four quartiles and compared according to initial TIMI flow. RESULTS: When TIMI flow was compared according to quartiles of platelet aggregation in ASPI-test, we have found significantly higher frequency of TIMI-2 and TIMI-3 flow among patients with low values of ASPI-test, i.e. with stronger aspirin response (P=0.014). None of the patients in the highest quartile of ASPI-test had TIMI flow of 2 or 3. CONCLUSIONS: Patients with stronger antiplatelet response to aspirin therapy in acute STEMI are more likely to present with spontaneous IRA recanalization.

Drug-specific thienopyridine resistance in patient with recurrent coronary stent thrombosis.

A 56-year-old male was admitted for elective percutaneous coronary intervention. Four days later he developed subacute stent thrombosis in the proximal stent in his right coronary artery. Using the Multiplate(R) ASPI and ADP test, we detected combined aspirin and clopidogrel resistance. The doses of aspirin and clopidogrel were increased to 300 mg and 150 mg, respectively. This resulted with optimization of aspirin response, but clopidogrel resistance was doseindependent. Three days later, the patient developed a new episode of ST-elevation myocardial infarction due to recurrent subacute thrombosis in the proximal stent. Consequently, clopidogrel was switched to ticlopidine 250 mg twice daily with resultant optimal platelet inhibition in the ADP test and the patient became clinically stable. This case indicates the clinical benefit from routine assessment of platelet responsiveness to antiaggregation therapy in patients with stent thrombosis. Also, clopidogrel resistance is drug-specific and not necessarily a class-effect phenomenon. By modifying drugs' doses, type of thienopyridine, or both, we can optimize antiplatelet therapy and the clinical course.

Virtual bronchoscopy and 3D spiral CT reconstructions in the management of patient with bronchial cancer--our experience with Syngo 3D postprocessing software.

Multislice helical CT generated virtual bronchoscopy (VB) represents one of the most recent developments in three-dimensional computer aided visualisation techniques. VB allows non-invasive and relatively accurate 3D evaluation of tracheobronchal tree. We performed virtual bronchoscopy and in-space 3D volume analysis on CT-data set acquired from sixty-four-year old male with bronchial cancer in order to demonstrate advantages and disadvantages of these methods in diagnostics and preoperative management of metastatic bronchial cancer. Siemens Somatom Emotion 16 helical CT scanner was used for data acquisition. Data post-processing was done with 3D Syngo 2006G software package from Siemens medical systems. CT scanning of the thorax was performed in heavy smoker with an expansive T4N1M1 malignant process in a superior lobe of the right lung accompanied with large metastatic lesion attached on the right lateral chest wall. Metastatic lesions were also found in vertebral column. In-space 3D analysis followed with virtual bronchoscopy had revealed obstruction of apical branch of superior lobe segmental bronchus. External compression done by tumor to the superior segmental and right main bronchus was found. We concluded that multi-slice CT in connection with VB became a possible non-invasive alternative to bronchoscopy, if tissue samples are not required.