Heart Overload Research Articles

Is it safe to discontinue anticoagulant after surgical treatment of varicose vein disease, which caused pulmonary embolism?

Superficial vein thrombosis, which is mostly caused by lower extremity varicose vein disease, can be complicated by pulmonary embolism. At the same time, the optimal duration of anticoagulant therapy for pulmonary embolism originated from varicose vein thrombosis is still under debate. On the one hand, the presence of varicose veins is considered a small risk factor for the development of venous thromboembolic events, which persistence determines an increased risk of relapse and requires prolonged anticoagulant therapy. On the other hand, elimination of varicose veins is associated with reduced risk of subsequent venous thromboembolic events. The article describes a clinical case of recurrent pulmonary embolism after surgical treatment of varicose vein disease, which caused primary pulmonary embolism. A 45-year-old patient suffering from left lower extremity varicose vein disease for 5 years was admitted to the intensive care unit with suspected pulmonary embolism. The further examination revealed signs of thrombotic occlusion of the segmental and subsegmental branches of the pulmonary arteries bilaterally and the middle lobe branch of the right pulmonary artery, as well as signs of the right-sided heart overload. In this case, pulmonary embolism was found to originate from thrombosis of the trunk of the great saphenous vein ofthe left lower extremity with a proximal border at the level of the lower leg. No signs of deep vein involvement were detected. The parenteral anticoagulant therapy initiated in the hospital was followed by switching to therapeutic doses of rivaroxaban. The signs of recanalization of involved veins were identified after 6 months of treatment, and it was decided to perform endovenous laser coagulation of the trunk of the great saphenous vein combined with mini-phlebectomy of varicose tributaries on continuous oral anticoagulant therapy. The rivaroxaban therapy was completed a month after intervention. However, 7 days later the patient was diagnosed with repeated symptomatic pulmonary embolism, which originated from thrombosis of the left popliteal vein. It was recommended to resume anticoagulant therapy of indefinite duration. The article discusses the issues of optimal duration of treatment for pulmonary embolism originated from thrombosis of superficial varicose veins, as well as the possible timing of completion of anticoagulant therapy after the intervention.

Right heart overload – possible long-term sequelae of Covid-19: a narrative review

The United Nations announced the COVID-19 Pandemic in March 2019, and since then, many efforts have been made to understand better the multiple consequences of the virus on one's health. Notably, such viral infection leads to an increase in the formation of thrombi and microthrombi. However, mechanisms are not precise yet, neither are these complication consequences and management. It is essential to acknowledge these aspects of the disease, so patients receive better health care when dealing with COVID-19. This article's extensive search involved PubMed, SCOPUS, Cochrane, and Google Scholar databases; authors used keywords to find relevant studies on the subject. SARS-CoV2 creates a pro-thrombotic state through direct endothelial damage and a cytokine storm, affecting the lung, among other organs, leading to hypoxia and a rise in vascular resistance. Increased vascular resistance makes patients prone to cardiac stress, with a known association with right heart failure, among other insults to the heart. This condition affects both outpatients and inpatients, hypertension being a significant risk factor. The cardiac damage can be observed by cardiac injury biomarkers, imaging, and heart failure symptoms. Considering the massive number of infected during the pandemic, we suggest that right heart failure secondary to increased vascular resistance in the COVID/post-COVID state presents as a long-term sequel of the infection. Moreover, we believe it deserves attention so that patients may receive early and adequate health care.

Hydrodynamic Transfection of Hepatocytes for the Study of Hepatocellular Carcinogenesis.

Hydrodynamic tail vein injection (HTVi), also called hydrodynamic gene transfer (HGT), is attracting increasing interest for modeling hepatic carcinogenesis. This highly versatile approach reproducibly provides efficient in vivo transfection of hepatocytes with naked DNA. Here, we give an in-depth description of the injection procedure, which is key for the success of the method. HTVi requires the injection of a large volume of a solution containing plasmids into the tail vein of the mouse. The transient right heart overload created by the injection forces the blood to flow back into the hepatic veins, enlarging the endothelial fenestrae and permeabilizing a fraction of hepatocytes for a few seconds. This results in the uptake of plasmids by the permeabilized hepatocytes, giving rise to their in vivo transfection. Including the Sleeping Beauty transposon system among the injected plasmids leads to the stable transfection of a subset of hepatocytes. HTVi is a powerful technique which enables numerous applications in liver cancer biology, such as a study of oncogene cooperation, of tumor heterogeneity, and interaction with the tumor microenvironment.

Elevated growth differentiation factor 15 is associated with echocardiographic markers of right heart overload in atrial fibrillation.

Elevated growth differentiation factor 15 is associated with echocardiographic markers of right heart overload in atrial fibrillation.

Mechanical thrombectomy in intermediate- and high-risk acute pulmonary embolism: haemodynamic outcome at 3 months

Abstract Background Haemodynamic data months after mechanical thrombectomy for pulmonary embolism (PE) are scarce. Aims To assess the haemodynamic effects of mechanical thrombectomy in acute PE with right heart overload. Methods In this prospective, open-label study, patients with acute symptomatic, computed tomography-documented PE with signs of right heart overload underwent mechanical thrombectomy using the FlowTriever System. Right heart catheterization was performed immediately before and after thrombectomy and after three months. Transthoracic echocardiography was performed before thrombectomy, discharge, and at three months. This analysis was done after the first 20 patients completed their three months of follow-up. Results Twenty-nine patients (34% female) underwent mechanical thrombectomy, of which 20 completed three months follow-up with right heart catheterization. Most patients (17%) were at high or intermediate-high (76%) risk and had bilateral pulmonary embolisms (79%). Before thrombectomy, systolic pulmonary arterial pressure (sPAP) was severely elevated (mean 51.3±11.6 mmHg). Mean sPAP dropped by -15.0 mmHg (95% confidence interval [CI]: -18.9 to -11.0; p<0.001) immediately following the procedure and continued to decrease from post-thrombectomy to three months (-6.4 mmHg, 95% CI: -10-0 to -2.9; p=0.002) (Figure). Right ventricle (RV)/left ventricle (LV) ratio immediately reduced within two days by -0.37 (95% CI: -0.47 to -0.27; p<0.001). The proportion of patients with a TAPSE/sPAP ratio <0.31 mm/mmHg decreased from 28% at baseline to 0% before discharge and at three months (p=0.007). There were no procedure-related major adverse events. Conclusions Mechanical thrombectomy for acute PE was safe and immediately reduced PAP and improved right heart function. The reduction in PAP was maintained at three months follow-up.Systolic pulmonary artery pressure

Mechanical thrombectomy in intermediate- and high-risk acute pulmonary embolism: hemodynamic outcomes at three months

BackgroundMechanical thrombectomy has been shown to reduce thrombus burden and pulmonary artery pressure (PAP) and to improve right ventricular (RV) function in patients with high-risk or intermediate-high-risk pulmonary embolism (PE). As hemodynamic data after mechanical thrombectomy for PE are scarce, we aimed to assess the hemodynamic effects of mechanical thrombectomy in acute PE with right heart overload.MethodsIn this prospective, open-label study, patients with acute symptomatic, computed tomography-documented PE with signs of right heart overload underwent mechanical thrombectomy using the FlowTriever System. Right heart catheterization was performed immediately before and after thrombectomy and after three months. Transthoracic echocardiography was performed before thrombectomy, discharge, and at three months. This analysis was done after 20 patients completed three months of follow-up.ResultsTwenty-nine patients (34% female) underwent mechanical thrombectomy, of which 20 completed three months follow-up with right heart catheterization. Most patients were at high (17%) or intermediate-high (76%) risk and had bilateral PE (79%). Before thrombectomy, systolic PAP (sPAP) was severely elevated (mean 51.3 ± 11.6 mmHg). Mean sPAP dropped by -15.0 mmHg (95% confidence interval [CI]: -18.9 to -11.0; p < 0.001) immediately after the procedure and continued to decrease from post-thrombectomy to three months (-6.4 mmHg, 95% CI: -10-0 to -2.9; p = 0.002). RV/left ventricular (LV) ratio immediately reduced within two days by -0.37 (95% CI: -0.47 to -0.27; p < 0.001). The proportion of patients with a tricuspid annular plane systolic excursion (TAPSE)/sPAP ratio < 0.31 mm/mmHg decreased from 28% at baseline to 0% before discharge and at three months (p = 0.007). There were no procedure-related major adverse events.ConclusionsMechanical thrombectomy for acute PE was safe and immediately reduced PAP and improved right heart function. The reduction in PAP was maintained at three months follow-up.

Comprehensive Treatment of Disseminated Fibrous Cavernous Pulmonary Tuberculosis with Extrapleural Thoracoplasty by Mesh Implant

The objective: to increase the effectiveness of comprehensive treatment of patients with advanced fibrous cavernous pulmonary tuberculosis using the new method of extrapleural upper-posterior thoracoplasty with a mesh implant.Subjects and Methods. It was an open, prospective, randomized, controlled study of treatment outcomes of 233 patients with fibrous cavernous pulmonary tuberculosis who had contraindications to resection surgery. Patients were divided into three groups depending on the type of thoracoplasty: thoracoplasty with a mesh implant was performed in 70 patients, thoracoplasty according to Bjork - in 60 people, and traditional upper-posterior thoracoplasty - in 103 patients.Results. In operated patients, additional support with a mesh implant during the formation of a new pleural dome reduced pathological flotation of chest organs, which prevented decreased respiratory function, the right heart overload, and protected from the development of bronchopulmonary complications in the early postoperative period. The chances of cavity healing and sputum conversion by the discharge from hospital increased by 3,3 times (OR=3,3; 95% CI 1,6-6,7), a year later by 3,0 times (OR=3,0; 95% CI 1,48-7,5); in the long-term assessment it increased chances of survival by 4,8 times (OR=4,8; 95% CI 1,4-16,4) versus the Bjork operation and traditional upper-posterior thoracoplasty.

Even non-expert radiologists report chronic thromboembolic pulmonary hypertension (CTEPH) on CT pulmonary angiography with high sensitivity and almost perfect agreement.

To assess the diagnostic performance and interobserver agreement of CT pulmonary angiography (CTPA) in the detection of chronic thromboembolic pulmonary hypertension (CTEPH) and its features among radiologists of different levels of experience. In this retrospective, single-center, single-blinded study, three radiologists with different levels of experience in CT imaging (R1:15 years, R2:6 years, and R3:3 years) evaluated CTPA of 51 patients ultimately diagnosed with CTEPH (European Society of Cardiology guidelines) and 49patients without CTEPH in random order to assess the presence of CTEPH, its features in the pulmonary artery tree, proximal level of involvement, bronchial artery hypertrophy, mosaic perfusion, and right heart overload. CTPAs of 51 patients with CTEPH (median age, 66 years (IQR 56-72), 28 men) and 49 patients without CTEPH (median age, 65 years (IQR 50-74), 25 men) were evaluated. The sensitivity and specificity for the detection of CTEPH was 100% (all radiologists) and 100% (R1), 96% (R2), and 96%(R3) with almost perfect agreement (κ = 0.95). The sensitivity and specificity for detecting CTEPH by mosaic perfusion would be 89% (95%CI 83-93%) and 81% (74-87%). The level of pulmonary artery involvement was reported with moderate agreement (κ = 0.54, 95%CI 0.40-0.65). Substantial agreement was found in the evaluation of mosaic attenuation (κ = 0.75, 95%CI 0.64-0.84), right heart overload (κ = 0.68, 95%CI 0.56-0.79), and bronchial artery hypertrophy (0.71, 95%CI 0.59-0.82) which were the best predictors of CTEPH (p < 0.0001). CTPA has high sensitivity and specificity in detecting CTEPH and almost perfect agreement among radiologists of different levels of expertise. CT pulmonary angiography can be used as a first-line imaging modality in patients with suspected chronic thromboembolic pulmonary hypertension (CTEPH) even when interpreted by non-CTEPH experts. • CT pulmonary angiography has high sensitivity and specificity in detecting chronic thromboembolic pulmonary hypertension (CTEPH) and almost perfect interobserver agreement among radiologists of different levels of expertise. • Substantial agreement exists in the assessment of mosaic attenuation, right heart overload, and bronchial artery hypertrophy, which are the best predictors of CTEPH.

C44 ATRIAL SEPTAL ABNORMALITIES: A CASE OF DOUBLE INTERATRIAL SEPTUM

Abstract The Case A 41–year–old asymptomatic male was referred to our cardiology outpatient clinic for diagnostic evaluation of a suspected bicuspid aortic valve at transthoracic echocardiography. Trans–oesophageal imaging ruled–out the bicuspid aortic valve, but detected an accessory membrane lining the interatrial septum with a double–layered appearance encompassing most of the fossa ovalis. Agitated saline infusion demonstrated an inter–atrial communication with right–to–left shunt under Valsalva manoeuvre. Cardiovascular magnetic resonance cine imaging confirmed the presence of a double interatrial septum featuring a midline recess enclosed by the two septa. Under end–expiratory breath–holding conditions, a transient right–to–left shunt was observed confirming the echocardiographic evaluation (Panel 1). No history of cerebrovascular disease and no clinical or imaging findings of right heart overload were registered. Discussion Double interatrial septum is a rare congenital condition, by morphological side, allegedly associated with an increased risk of left–sided embolic events due to blood stasis within the accessory interatrial chamber, that is often found in continuity with both atria through patent foramen ovale or additional septal fenestrations. In this case, multimodality imaging effectively was able to detect the presence of this rare atrial septal abnormality and to distinguish that from others alterations of the interatrial septum shown in the table below (Table 1). Nevertheless, the clinical significance of double interatrial septum remains uncertain, no clear relationship with embolic stroke is known and no recommendation can be made regarding the decision–making for long–term anti–thrombotic management. High quality evidences are needed to evaluate whether double atrial septum or other atrial septal abnormalities might be considered as actionable risk factors of ischemic stroke or not.

A simply calculated nutritional index provides clinical implications in patients undergoing transcatheter aortic valve replacement

BackgroundMalnutrition is associated with adverse outcomes in patients with aortic stenosis. The Triglycerides × Total Cholesterol × Body Weight Index (TCBI) is a simple scoring model to evaluate the status of nutrition. However, the prognostic relevance of this index in patients undergoing transcatheter aortic valve replacement (TAVR) is unknown. This study aimed to evaluate the association of the TCBI with clinical outcomes in patients undergoing TAVR.MethodsA total of 1377 patients undergoing TAVR were evaluated in this study. The TCBI was calculated by the formula; triglyceride (mg/dL) × total cholesterol (mg/dL) × body weight (kg)/1000. The primary outcome was all-cause mortality within 3 years.ResultsPatients with a low TCBI, based on a cut-off value of 985.3, were more likely to have elevated right atrial pressure (p = 0.04), elevated right ventricular pressure (p < 0.01), right ventricular systolic dysfunction (p < 0.01), tricuspid regurgitation ≥ moderate (p < 0.01). Patients with a low TCBI had a higher cumulative 3-year all-cause (42.3% vs. 31.6%, p < 0.01; adjusted HR 1.36, 95% CI 1.05–1.77, p = 0.02) and non-cardiovascular mortality (15.5% vs. 9.1%, p < 0.01; adjusted HR 1.95, 95% CI 1.22–3.13, p < 0.01) compared to those with a high TCBI. Adding a low TCBI to EuroSCORE II improved the predictive value for 3-year all-cause mortality (net reclassification improvement, 0.179, p < 0.01; integrated discrimination improvement, 0.005, p = 0.01).ConclusionPatients with a low TCBI were more likely to have right-sided heart overload and exhibited an increased risk of 3-year mortality. The TCBI may provide additional information for risk stratification in patients undergoing TAVR.Graphical abstract

New characteristics in ECG induced by ultra-high altitude hypoxia

The partial pressure of oxygen decreases significantly with altitude elevation. Adaptive pathophysiological reactions and non-special electrocardiogram(ECG) changes are common in healthy individuals who are exposed to high altitude environments (greater than2500 m). However, previous literatures reported did not fully reflect the characteristics of the plateau ECG changes. A 27-year-old man living for more than 400 days at an ultra-high altitude (5400 m) presented with a rare but urgent ECG features including a right deviation of the electrical axis, pathological Q-wave, a poor increase of R-wave, and T-wave bidirectional/inversion. The erythrocytosis, pulmonary artery pressure, right heart overload and the reversible dynamic evolution of ECGs were gradually improved after he was rapidly transferred to the a low-altitude hospital. This study may provide a new feature of high-altitude induced ECG changes, indicate the potential mechanismand therapeutic value.

The role of computed tomography pulmonary angiography in COVID-19 patients with suspected pulmonary embolism.

This study is aimed to determine the location and distribution of pulmonary embolism (PE) and presence of signs potentially indicative of right heart overload on computed tomography pulmonary angiography (CTPA) in COVID-19 and non-COVID-19 patients. We also evaluated the extent and severity of COVID-19-associated lung changes in relation to PE. The total number of 1,698 patients with CTPA included in the study were divided into 2 groups according to their COVID-19 status and each group was divided into 2 subgroups based on their PE status. These groups and subgroups were compared in terms of location of PE, diameter of pulmonary artery, right heart strain, ground-glass opacities (GGO), consolidations and other imaging features. In COVID-19 patients, there was a significant predominance of PE in peripheral branches of pulmonary artery (p < 0.001). There was an increased right-to-left ratio of ventricular diameters in cases with PE (p = 0.032 in patients with COVID-19 and p < 0.001 in non-COVID-19 patients). There was no association between the extent and severity of the disease and distribution of PE. COVID-19 is associated with a higher incidence of peripheral location of PE and presence of GGO. There were signs indicative of right heart overload in cases with PE regardless of COVID-19 (Tab. 3, Fig. 1, Ref. 29) Keywords: COVID-19, computed tomography, CTPA, pneumonia, pulmonary embolism.

The thromboxane receptor antagonist NTP42 promotes beneficial adaptation and preserves cardiac function in experimental models of right heart overload.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary artery pressure leading to right ventricular (RV) failure. While current PAH therapies improve patient outlook, they show limited benefit in attenuating RV dysfunction. Recent investigations demonstrated that the thromboxane (TX) A2 receptor (TP) antagonist NTP42 attenuates experimental PAH across key hemodynamic parameters in the lungs and heart. This study aimed to validate the efficacy of NTP42:KVA4, a novel oral formulation of NTP42 in clinical development, in preclinical models of PAH while also, critically, investigating its direct effects on RV dysfunction. The effects of NTP42:KVA4 were evaluated in the monocrotaline (MCT) and pulmonary artery banding (PAB) models of PAH and RV dysfunction, respectively, and when compared with leading standard-of-care (SOC) PAH drugs. In addition, the expression of the TP, the target for NTP42, was investigated in cardiac tissue from several other related disease models, and from subjects with PAH and dilated cardiomyopathy (DCM). In the MCT-PAH model, NTP42:KVA4 alleviated disease-induced changes in cardiopulmonary hemodynamics, pulmonary vascular remodeling, inflammation, and fibrosis, to a similar or greater extent than the PAH SOCs tested. In the PAB model, NTP42:KVA4 improved RV geometries and contractility, normalized RV stiffness, and significantly increased RV ejection fraction. In both models, NTP42:KVA4 promoted beneficial RV adaptation, decreasing cellular hypertrophy, and increasing vascularization. Notably, elevated expression of the TP target was observed both in RV tissue from these and related disease models, and in clinical RV specimens of PAH and DCM. This study shows that, through antagonism of TP signaling, NTP42:KVA4 attenuates experimental PAH pathophysiology, not only alleviating pulmonary pathologies but also reducing RV remodeling, promoting beneficial hypertrophy, and improving cardiac function. The findings suggest a direct cardioprotective effect for NTP42:KVA4, and its potential to be a disease-modifying therapy in PAH and other cardiac conditions.

Prediction of Heart and Liver Iron Overload in β-Thalassemia Major Patients Using Machine Learning Methods

Patients with β-thalassemia major (β-TM) face a wide range of complications as a result of excess iron in vital organs, including the heart and liver. Our aim was to find the best predictive machine learning (ML) model for assessing heart and liver iron overload in patients with β-TM. Data from 624 β-TM patients were entered into three ML models using random forest (RF), gradient boost model (GBM), and logistic regression (LR). The data were classified and analyzed by R software. Four evaluation metrics of predictive performance were measured: sensitivity, specificity, accuracy, and area under the curve (AUC), operating characteristic curve. For heart iron overload, the LR had the highest predictive performance based on AUC: 0.68 [95% CI (95% confidence interval): 0.60, 0.75]. The GBM also had the highest specificity (69.0%) and accuracy (67.0%). Most sensitivity is also acquired with LR (75.0%). For liver iron overload, the highest performance based on AUC was observed with RF, AUC: 0.68 (95% CI: 0.59, 0.76). The RF showed the highest accuracy (66.0%) and specificity (66.0%), while the LR had the highest sensitivity (84.0%). Ferritin, duration of transfusion, and age were determined as the most effective predictors of iron overload in both heart and liver. Logistic regression LR was determined to be the strongest method to predict cardiac and RF values for liver iron overload in patients with β-TM. Older thalassemia patients with a high serum ferritin (SF) level and a longer duration of transfusion therapy were more prone to heart and liver iron overload.

Liver T1/T2 values with cardiac MRI during respiration.

Assessing the hepatic status of children with CHD is very important in the post-operative period. This study aimed to assess the usefulness of paediatric liver T1/T2 values and to evaluate the impact of respiration on liver T1/T2 values. Liver T1/T2 values were evaluated in 69 individuals who underwent cardiac MRI. The mean age of the participants was 16.2 ± 9.8 years. Two types of imaging with different breathing methods were possible in 34 participants for liver T1 values and 10 participants for liver T2 values. The normal range was set at 620-830 msec for liver T1 and 25-40 ms for liver T2 based on the data obtained from 17 healthy individuals. The liver T1/T2 values were not significantly different between breath-hold and free-breath imaging (T1: 769.4 ± 102.8 ms versus 763.2 ± 93.9 ms; p = 0.148, T2: 34.9 ± 4.0 ms versus 33.6 ± 2.4 ms; p = 0.169). Higher liver T1 values were observed in patients who had undergone Fontan operation, tetralogy of Fallot operation, or those with chronic viral hepatitis. There was a trend toward correlation between liver T1 values and liver stiffness (R = 0.65, p = 0.0004); and the liver T1 values showed a positive correlation with the shear wave velocity (R = 0.62, p = 0.0006). Liver T1/T2 values were not affected by breathing patterns. Because liver T1 values tend to increase with right heart overload, evaluation of liver T1 values during routine cardiac MRI may enable early detection of future complications.

Tofogliflozin, a sodium-glucose cotransporter 2 inhibitor, improves pulmonary vascular remodeling due to left heart disease in mice

BackgroundGroup 2 pulmonary hypertension (PH) represents PH caused by left heart disease (PH-LHD). LHD induces left-sided filling and PH, finally leading to pulmonary vascular remodeling. Tofogliflozin (TOFO) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used in the treatment of diabetes. Recent studies have shown that SGLT2 inhibitors have beneficial effects on heart failure, but the effects of SGLT2 inhibitors on PH-LHD remain unclear. We hypothesized that TOFO has protective effects against pulmonary vascular remodeling in PH-LHD mice. MethodsWe generated two murine models of PH-LHD: a transverse aortic constriction (TAC) model; and a high-fat diet (HFD) model. C57BL/6J mice were subjected to TAC and treated with TOFO (3 mg/kg/day) for 3 weeks. AKR/J mice were fed HFD and treated with TOFO (3 mg/kg/day) for 20 weeks. We then measured physical data and right ventricular systolic pressure (RVSP) and performed cardiography. Human pulmonary artery smooth muscle cells (PASMCs) were cultured and treated with TOFO. ResultsMice treated with TOFO demonstrated increased urine glucose levels. TAC induced left ventricular hypertrophy and increased RVSP. TOFO treatment improved RVSP. HFD increased body weight (BW) and RVSP compared with the normal chow group. TOFO treatment ameliorated increases in BW and RVSP induced by HFD. Moreover, PASMCs treated with TOFO showed suppressed migration. ConclusionsTOFO treatment ameliorated right heart overload and pulmonary vascular remodeling for PH-LHD models, suggesting that SGLT2 inhibitors are effective for treating PH-LHD.

PFO Closure after Pulmonary Valve Intervention in Patients with Hypoxemia Due to Right-to-Left Intracardiac Shunt

Four patients with pulmonary valve (PV) disease and patent foramen ovale (PFO) presented with dyspnea on exertion. Work-up revealed hypoxemia secondary to right-to-left intracardiac shunt. We demonstrate that correction of the primary culprit right heart overload lesion via PV replacement enabled safe PFO repair and resolution of hypoxemia.

Modeling liver hereditary hemorrhagic telangiectasia with right heart overload to the core of liver sinusoidal endothelial cells.

1 INSERM, INRAE Univ RennesNutrition Metabolism and CancerRennesFrance *Correspondence Orlando Musso, INSERM, INRAE, Univ Rennes, Nutrition Metabolism and Cancer, Rennes, France. Email: [email protected]

Predictive value of the Fibrosis-4 index in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

Liver dysfunction is associated with an increased risk of mortality after cardiac interventions. The Fibrosis-4 (FIB-4 index), a marker of hepatic fibrosis, has been associated with a worse prognosis in heart failure. The prognostic relevance of the index in patients undergoing transcatheter aortic valve replacement (TAVR) is unknown. The aim of this study was to evaluate the clinical implications associated with the FIB-4 index in patients undergoing TAVR. Between May 2012 and June 2019, 941 patients undergoing TAVR were stratified into a low or high FIB-4 index group, based on a cutoff value that was determined according to a receiver operating characteristic curve predicting 1-year all-cause mortality. Patients with a high FIB-4 index (n = 480), based on the cutoff value of 1.82, showed higher rates of pulmonary hypertension (43.8% vs. 31.8%, p < 0.01), right-ventricular systolic dysfunction (29.5% vs. 19.2%, p < 0.01) and larger inferior vena cava diameter (1.6 ± 0.6cm vs. 1.3 ± 0.6cm, p < 0.01) than patients with a low FIB-4 index (n = 461). Furthermore, a high FIB-4 index was associated with a significantly higher cumulative 1-year all-cause mortality (17.5% vs. 10.2%, p < 0.01) and non-cardiovascular mortality (12.1% vs. 2.5%, p < 0.01), compared to a low FIB-4 index. Multivariable analysis revealed that a high FIB-4 index was independently associated with all-cause mortality (HR: 1.75 [95% CI: 1.18-2.59], p < 0.01). A high FIB-4 index is associated with right-sided heart overload and an increased risk of mortality in patients undergoing TAVR. The FIB-4 index may be useful as an additional predictor of outcomes in these patients.

P1511: EFFICACY AND SAFETY OF COMBINATION IRON CHELATION THERAPY WITH DEFERIPRONE AND DEFERASIROX IN PATIENTS WITH Β-THALASSEMIA MAJOR: A SYSTEMATIC LITERATURE REVIEW

Background: Iron overload can occur in patients with thalassemia syndromes because of hyperabsorption and/or frequent blood transfusions. Currently, 3 iron chelators are approved for clinical use: deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX). Combination iron chelation therapy may be prescribed for patients who do not adequately respond to monotherapy, have increased heart and/or liver iron overload, or have dose-dependent toxicity. It is important to optimize chelation to reduce iron-associated morbidity and early mortality and to improve quality of life. Oral DFP is typically administered as a monotherapy or in combination with DFO or DFX. Combination therapy was approved for clinical use by the European Medicines Agency in 2016; additionally, a recent British Society for Haematology guideline states that DFP+DFX is a highly effective combination therapy, although the safety and efficacy of DFX in combination with other iron chelators is not well established. Aims: A systematic literature review was conducted to evaluate the efficacy and safety profile of combination chelation therapy with DFP+DFX in patients with transfusion dependent β-thalassemia major (TDT). Methods: A systematic search was performed of the Embase and MEDLINE databases to identify trials related to the use of combination iron chelation therapy (DFP+DFX) in patients with TDT. The literature search was conducted in May 2021 and was not restricted to a specific start date. The search strings were established by logical association of appropriate words and MESH terms. The publications were screened based on a priori exclusion and inclusion criteria (eg, case-report exclusion). Results: Eight clinical study publications (7 prospective, 1 retrospective) of 1725 screened articles assessed the DFP+DFX combination for a total of 181 patients (Table). One publication was a pharmacokinetic (PK) study. Of the 7 studies, 6 reported a consistent reduction in at least 1 of the 3 studied endpoints (serum ferritin, liver, and cardiac iron). The PK study reported an additive effect in the total iron excretion in comparison with monotherapy. The adverse events reported with DFP+DFX were consistent with what has previously been reported for DFP or DFX monotherapy; no new adverse events were observed. The most common adverse events across the 7 studies included gastrointestinal symptoms, elevation in alanine aminotransferase and/or aspartate aminotransferase, arthralgia or joint symptoms, an increase in creatinine levels, proteinuria, and red-colored urine. The numbers of patients reported with neutropenia and thrombocytopenia were low (neutropenia, n=7 patients; thrombocytopenia, n=8 patients); agranulocytosis was not observed. Two studies reported serious adverse events, of which 1 (acute cholecystitis) was related to treatment. Image:Summary/Conclusion: This systematic literature review suggests that DFP+DFX combination iron chelation therapy can be a highly effective therapeutic option for improving iron overload, with an acceptable tolerability profile. This review supports the safety and efficacy of the combination, as approved by the EMA. Limitations of this analysis include small sample size and nonrandomization in most studies.