Search

Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p < .001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01-1.14] per 10 ml/min/1.73 m decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m (HR 2.21 [95% CI, 1.23-3.99] compared to eGFR ≥90 ml/min/1.73 m ). A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

INTRODUCTION: It has been recognized that increasing body mass index (BMI) is associated with improved outcome from immune checkpoint inhibitors (ICIs) in patients with various malignancies including non-small cell lung cancer (NSCLC). However, it is unclear whether baseline BMI may influence outcomes from first-line chemoimmunotherapy combinations. METHODS: In this international multicenter study, we evaluated the association between baseline BMI, progression-free survival (PFS) and overall survival (OS) in a cohort of patients with stage IV NSCLC consecutively treated with first-line chemoimmunotherapy combinations. BMI was categorized according to WHO criteria. Results: Among the 853 included patients, 5.3% were underweight; 46.4% were of normal weight; 33.8% were overweight; and 14.5% were obese. Overweight and obese patients were more likely aged ≥70 years (p=0.00085), never smokers (p<0.0001), with better baseline Eastern Cooperative Oncology Group-Performance Status (p=0.0127), and had lower prevalence of central nervous system (p=0.0002) and liver metastases (p=0.0395). Univariable analyses showed a significant difference in the median OS across underweight (15.5 months), normal weight (14.6 months), overweight (20.9 months), and obese (16.8 months) patients (log-rank: p=0.045, log rank test for trend: p=0.131), while no difference was found with respect to the median PFS (log-rank for trend: p=0.510). Neither OS nor PFS was significantly associated with baseline BMI on multivariable analysis. CONCLUSIONS: In contrast to what was observed in the context of chemotherapy-free ICI-based regimens, baseline BMI does not affect clinical outcomes from chemoimmunotherapy combinations in patients with advanced NSCLC.

Cardiovascular diseases represent a major cause of morbidity and mortality, necessitating research to improve diagnostics, and to discover and test novel preventive and curative therapies. All of which warrant experimental models that recapitulate human disease. The translation of basic science results to clinical practice is a challenging task. In particular for complex conditions such as cardiovascular diseases, which often result from multiple risk factors and co-morbidities. This difficulty might lead some individuals to question the value of animal research, citing the translational 'valley of death', which largely reflects the fact that studies in rodents are difficult to translate to humans. This is also influenced by the fact that new, human-derived in vitro models can recapitulate aspects of disease processes. However, it would be a mistake to think that animal models cannot provide a vital step in the translational pathway as they do provide important pathophysiological insights into disease mechanisms particularly on a organ and systemic level. While stem cell-derived human models have the potential to become key in testing toxicity and effectiveness of new drugs, we need to be realistic, and carefully validate all new human-like disease models. In this position paper, we highlight recent advances in trying to reduce the number of animals for cardiovascular research ranging from stem cell-derived models to in situ modelling of heart properties, bioinformatic models based on large datasets, and improved current animal models, which show clinically relevant characteristics observed in patients with a cardiovascular disease. We aim to provide a guide to help researchers in their experimental design to translate bench findings to clinical routine taking the replacement, reduction and refinement (3R) as a guiding concept.

INTRODUCTION: Ankle arthropathy is highly prevalent among people with haemophilia (PwH), even with prophylaxis, and leads to pain and disability. Mechanisms and consequences of painful symptoms related to ankle arthropathy have not been extensively studied. METHODS: A consecutive sample of 30 adult PwH was included (60 ankles). Ankle structure was assessed with magnetic resonance imaging (IPSG-MRI) and ultrasound (HEAD-US). The HJHS 2.1 assessed function of ankles and knees. Physical functioning was assessed with the Timed Up and Go test, the 2-Minute Walking Test and activity limitations with the HAL questionnaire. Health-related quality of life was evaluated using the EQ-5D-5L questionnaire. Overall pain severity was examined using the Brief Pain Inventory questionnaire and ankle pain intensity with a visual analogue scale. Pressure pain thresholds with an algometer assessed pain sensitivity. Spearman correlations were used to calculate interrelations between joint structure, function and pain. RESULTS: Twenty-five PwH (83%) reported ≥1 painful joint, with 67% reporting the ankle as most painful joint. MRI-confirmed abnormalities were seen in 76% of talocrural and 55% of subtalar joints. HEAD-US abnormalities were seen in 93% of the ankles. A large variation was seen in pain sensitivity at the ankle. While moderate to high correlations were observed between ankle structure and HJHS, no meaningful correlations were found between MRI-scores and pain intensity or sensitivity. CONCLUSIONS: Structural joint damage is present in many ankles but is not related to pain in PwH. Further studies should consider somatosensory nervous system dysfunction in PwH as contributing factor to painful ankle arthropathy.

BACKGROUND: Dietary interventions targeting the gut microbiota have been proposed as innovative strategies to improve obesity-associated metabolic disorders. Increasing physical activity (PA) is considered as a key behavioral change for improving health. We have tested the hypothesis that changing the PA status during a nutritional intervention based on prebiotic supplementation can alter or even change the metabolic response to the prebiotic. We confirm in obese subjects and in high-fat diet fed mice that performing PA in parallel to a prebiotic supplementation is necessary to observe metabolic improvements upon inulin. METHODS: A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in obese participants who received 16 g/day native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Primary outcomes concern the changes on the gut microbiota composition, and secondary outcomes are related to the measures of anthropometric and metabolic parameters, as well as the evaluation of PA. Among the 106 patients who completed the study, 61 patients filled a questionnaire for PA before and after intervention (placebo: n = 31, prebiotic: n = 30). Except the dietitian (who provided dietary advices and recipes book), all participants and research staff were blinded to the treatments and no advices related to PA were given to participants in order to change their habits. In parallel, a preclinical study was designed combining both inulin supplementation and voluntary exercise in a model of diet-induced obesity in mice. RESULTS: Obese subjects who increased PA during a 3 months intervention with inulin-enriched diet exhibited several clinical improvements such as reduced BMI (- 1.6 kg/m2), decreased liver enzymes and plasma cholesterol, and improved glucose tolerance. Interestingly, the regulations of Bifidobacterium, Dialister, and C

Nearly half of all patients with heart failure (HF) have a normal left ventricular (LV) ejection fraction (EF) and the condition is termed heart failure with preserved ejection fraction (HFpEF). It is assumed that in these patients HF is due primarily to LV diastolic dysfunction. The prognosis in HFpEF is almost as severe as in HF with reduced EF (HFrEF). In contrast to HFrEF where drugs and devices are proven to reduce mortality, in HFpEF there has been limited therapy available with documented effects on prognosis. This may reflect that HFpEF encompasses a wide range of different pathological processes, which multimodality imaging is well placed to differentiate. Progress in developing therapies for HFpEF has been hampered by a lack of uniform diagnostic criteria. The present expert consensus document from the European Association of Cardiovascular Imaging (EACVI) provides recommendations regarding how to determine elevated LV filling pressure in the setting of suspected HFpEF and how to use multimodality imaging to determine specific aetiologies in patients with HFpEF.

Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear. To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls. This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA. Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year). The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index). Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 nonc

Nonadherence to antihypertensive medication is common, especially in those with apparent treatment-resistant hypertension (true treatment-resistant hypertension requires exclusion of nonadherence), and its routine detection is supported by clinical guidelines. Chemical adherence testing is a reliable and valid method to detect adherence, yet methods are unstandardized and are not ubiquitous. This article describes the principles of chemical adherence testing for hypertensive patients and provides a set of recommendations for centers wishing to develop the test. We recommend testing should be done in either of two instances: (1) in those who have resistant hypertension or (2) in those on 2 antihypertensives who have a less than 10 mm Hg drop in systolic blood pressure on addition of the second antihypertensive medication. Furthermore, we recommend that verbal consent is secured before undertaking the test, and the results should be discussed with the patient. Based on medications prescribed in United Kingdom, European Union, and United States, we list top 20 to 24 drugs that cover >95% of hypertension prescriptions which may be included in the testing panel. Information required to identify these medications on mass spectrometry platforms is likewise provided. We discuss issues related to ethics, sample collection, transport, stability, urine versus blood samples, qualitative versus quantitative testing, pharmacokinetics, instrumentation, validation, quality assurance, and gaps in knowledge. We consider how to best present, interpret, and discuss chemical adherence test results with the patient. In summary, this guidance should help clinicians and their laboratories in the development of chemical adherence testing of prescribed antihypertensive drugs.

Transradial access (TRA) has become the default access method for coronary diagnostic and interventional procedures. As compared to transfemoral access, TRA has been shown to be safer, cost-effective and more patient-friendly. Radial artery occlusion (RAO) represents the most frequent complication of TRA, and precludes future coronary procedures through the radial artery, the use of the radial artery as a conduit for coronary artery bypass grafting or as arteriovenous fistula for patients on hemodialysis. Recently, distal radial access (DRA) has emerged as a promising alternative to TRA, yielding potential for minimizing the risk of RAO. However, an international multicenter randomized comparison between DRA, and conventional TRA with respect to the rate of RAO is still lacking. DISCO RADIAL is a prospective, multicenter, open-label, randomized, controlled, superiority trial. A total of 1300 eligible patients will be randomly allocated to undergo coronary angiography and/or percutaneous coronary intervention (PCI) through DRA or TRA using the 6 Fr Glidesheath Slender sheath introducer. Extended experience with both TRA and DRA is required for operators' eligibility and optimal evidence-based best practice to reduce RAO systematically implemented by protocol. The primary endpoint is the incidence of forearm RAO assessed by vascular ultrasound at discharge. Several important secondary endpoints will also be assessed, including access-site cross-over, hemostasis time, and access-site related complications. The DISCO RADIAL trial will provide the first large-scale multicenter randomized evidence comparing DRA to TRA in patients scheduled for coronary angiography or PCI with respect to the incidence of RAO at discharge.

INTRODUCTION: Recurrent bleeding in severe haemophilia B causes painful hemarthroses and reduces capacity for physical activity. Recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis results in low annualised bleeding rates, with the potential to improve patients' health-related quality of life (HRQoL). AIM: To present a post hoc analysis of data from B-LONG describing change over time in patient-reported outcomes associated with pain and physical activity. METHODS: Patients (≥12 years) who received weekly dose-adjusted or interval-adjusted rFIXFc prophylaxis and completed the Haemophilia-Specific QoL questionnaire for adolescents (Haemo-QoL) or adults (Haem-A-QoL) at baseline (BL) and end of study (EoS). Individual level changes in items of the 'Physical Health' and 'Sports and Leisure' domains, categorised as 'never/rarely/seldom' or 'sometimes/often/all the time', were analysed using McNemar's test to compare distribution of responses at EoS versus BL. RESULTS: At EoS versus BL, a significantly greater proportion of patients did not experience painful swellings (64% vs. 44%; P = .004), painful joints (44% vs. 28%; P = .003) or pain when moving (54% vs. 41%; P = .026). Additionally, at EoS versus BL, patients were less likely to avoid participating in sports like football (30% vs. 8%; P = .002), avoid sports due to their haemophilia (47% vs. 27%; P = .007), or experience difficulty walking as far as they wanted (63% vs. 43%; P = .001). The proportion of patients who played sports as much as the general population was numerically increased (52% vs. 37%; P = .033) at EoS versus BL. CONCLUSION: Results of the analysis suggest that over time, rFIXFc prophylaxis is associated with significant improvements in pain and physical functioning. This contributes to previous evidence of overall HRQoL improvements in patients with haemophilia B treated with rFIXFc.

Background: Non-invasive evaluation of left atrial structural and functional remodeling should be considered in all patients with persistent atrial fibrillation (AF) to optimal management. Speckle tracking echocardiography (STE) has been shown to predict AF recurrence after catheter ablation; however in most studies, patients had paroxysmal AF, and STE was performed while patients were in sinus rhythm. Aim: The aim of this study was to evaluate the ability of STE parameters acquired during persistent AF to assess atrial fibrosis measured by low voltage area, and to predict maintenance of sinus rhythm of catheter ablation. Methods: A total of 94 patients (69 men, 65 ± 9 years) with persistent AF prospectively underwent measurement of Global Peak Atrial Longitudinal Strain (GPALS), indexed LA Volume (LAVI), E/e′ ratio, and LA stiffness index (the ratio of E/e′ to GPALS) by STE prior to catheter ablation, while in AF. Low-voltage area (LVA) was assessed by electro-anatomical mapping and categorized into absent, moderate (>0 to <15%), and high (≥15%) atrial extent. AF recurrence was evaluated after 3 months of blanking. Results: Multivariable regression showed that LAVI, GPALS, and LA stiffness independently predicted LVA extent after correcting for age, glomerular filtration rate, and CHA2DS2-VASc score. Of all the parameters, LA stiffness index had the highest diagnostic accuracy (AUC 0.85), allowing using a cut-off value ≥0.7 to predict moderate or high LVA with 88% sensitivity and 47% specificity, respectively. In multivariable Cox analysis, both GPALS and LA stiffness were able to significantly improve the c statistic to predict AF recurrence (n = 40 over 9 months FU) over CHARGE-AF (p < 0.001 for GPALS and p = 0.01 for LA stiffness) or CHA2DS2-VASc score (p < 0.001 for GPALS and p = 0.02 for LA stiffness). GPALS and LA stiffness also improved the net reclassification index (NRI) over the CHARGE-AF index (NRI 0.67, 95% CI [0.33–1.13] for GPALS and NRI 0.73, 95% CI

Assessment of right ventricular (RV) function is crucial for the evaluation of the dyspnoeic patient and/or with systemic venous congestion and provides powerful prognostic insights. It can be performed using different imaging modalities including standard and advanced echocardiographic techniques, cardiac magnetic resonance imaging, computed tomography, and radionuclide techniques, which should be used in a complementary fashion. Each modality has strengths and weaknesses based on which the choice of their use and in which combination may vary according to the different clinical scenarios as will be detailed in this review. The conclusions from multiple studies using different imaging techniques are concordant: RV function can be reliably assessed and is a critical predictor of clinical outcomes.

Motion estimation in echocardiography plays an important role in the characterization of cardiac function, allowing the computation of myocardial deformation indices. However, there exist limitations in clinical practice, particularly with regard to the accuracy and robustness of measurements extracted from images. We therefore propose a novel deep learning solution for motion estimation in echocardiography. Our network corresponds to a modified version of PWC-Net which achieves high performance on ultrasound sequences. In parallel, we designed a novel simulation pipeline allowing the generation of a large amount of realistic B-mode sequences. These synthetic data, together with strategies during training and inference, were used to improve the performance of our deep learning solution, which achieved an average endpoint error of 0.07± 0.06mmper frame and 1.20±0.67mmbetween ED and ES on our simulated dataset. The performance of our method was further investigated on 30 patients from a publicly available clinical dataset acquired from a GE system. The method showed promise by achieving a mean absolute error of the global longitudinal strain of 2.5 ± 2.1% and a correlation of 0.77 compared to GLS derived from manual segmentation, much better than one of the most efficient methods in the state-of-the-art (namely the FFT-Xcorr block-matching method). We finally evaluated our method on an auxiliary dataset including 30 patients from another center and acquired with a different system. Comparable results were achieved, illustrating the ability of our method to maintain high performance regardless of the echocardiographic data processed.

No abstract available

Heart failure, mostly associated with cardiac hypertrophy, is a major cause of illness and death. Oxidative stress causes accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction, suggesting that mitochondria-targeted therapies could be effective in this context. The purpose of this work was to determine whether mitochondria-targeted therapies could improve cardiac hypertrophy induced by mitochondrial ROS. We used neonatal (NCMs) and adult (ACMs) rat cardiomyocytes hypertrophied by isoproterenol (Iso) to induce mitochondrial ROS. A decreased interaction between sirtuin 3 and superoxide dismutase 2 (SOD2) induced SOD2 acetylation on lysine 68 and inactivation, leading to mitochondrial oxidative stress and dysfunction and hypertrophy after 24 h of Iso treatment. To counteract these mechanisms, we evaluated the impact of the mitochondria-targeted antioxidant mitoquinone (MitoQ). MitoQ decreased mitochondrial ROS and hypertrophy in Iso-treated NCMs and ACMs but altered mitochondrial structure and function by decreasing mitochondrial respiration and mitophagy. The same decrease in mitophagy was found in human cardiomyocytes but not in fibroblasts, suggesting a cardiomyocyte-specific deleterious effect of MitoQ. Our data showed the importance of mitochondrial oxidative stress in the development of cardiomyocyte hypertrophy. We observed that targeting mitochondria by MitoQ in cardiomyocytes impaired the metabolism through defective mitophagy, leading to accumulation of deficient mitochondria.

Protein O-GlcNAcylation is increasingly recognized as an important cellular regulatory mechanism, in multiple organs including the heart. However, the mechanisms leading to O-GlcNAcylation in mitochondria and the consequences on their function remain poorly understood. In this study, we use an in vitro reconstitution assay to characterize the intra-mitochondrial O-GlcNAc system without potential cytoplasmic confounding effects. We compare the O-GlcNAcylome of isolated cardiac mitochondria with that of mitochondria acutely exposed to NButGT, a specific inhibitor of glycoside hydrolase. Amongst the 409 O-GlcNAcylated mitochondrial proteins identified, 191 display increased O-GlcNAcylation in response to NButGT. This is associated with enhanced Complex I (CI) activity, increased maximal respiration in presence of pyruvate-malate, and a striking reduction of mitochondrial ROS release, which could be related to O-GlcNAcylation of specific subunits of ETC complexes (CI, CIII) and TCA cycle enzymes. In conclusion, our work underlines the existence of a dynamic mitochondrial O-GlcNAcylation system capable of rapidly modifying mitochondrial function.

The study objective was to analyze survival and incidence of Fontan completion of patients with single-ventricle and concomitant unbalanced atrioventricular septal defect. Data from 4 Dutch and 3 Belgian institutional databases were retrospectively collected. A total of 151 patients with single-ventricle atrioventricular septal defect were selected; 36 patients underwent an atrioventricular valve procedure (valve surgery group). End points were survival, incidence of Fontan completion, and freedom from atrioventricular valve reoperation. Median follow-up was 13.4 years. Cumulative survival was 71.2%, 70%, and 68.5% at 10, 15, and 20 years, respectively. An atrioventricular valve procedure was not a risk factor for mortality. Patients with moderate-severe or severe atrioventricular valve regurgitation at echocardiographic follow-up had a significantly worse 15-year survival (58.3%) compared with patients with no or mild regurgitation (89.2%) and patients with moderate regurgitation (88.6%) (P = .033). Cumulative incidence of Fontan completion was 56.5%, 71%, and 77.6% at 5, 10, and 15 years, respectively. An atrioventricular valve procedure was not associated with the incidence of Fontan completion. In the valve surgery group, freedom from atrioventricular valve reoperation was 85.7% at 1 year and 52.6% at 5 years. The long-term survival and incidence of Fontan completion in our study were better than previously described for patients with single-ventricle atrioventricular septal defect. A concomitant atrioventricular valve procedure did not increase the mortality rate or decrease the incidence of Fontan completion, whereas patients with moderate-severe or severe valve regurgitation at follow-up had a worse survival. Therefore, in patients with single-ventricle atrioventricular septal defect when atrioventricular valve regurgitation exceeds a moderate degree, the atrioventricular valve should be repaired.

INTRODUCTION: A second peak of inhibitors has been reported in patients with severe haemophilia A (HA) aged >50 years in the UK.1 The reason for this suggested breakdown of tolerance in the ageing population is unclear, as is the potential impact of regular exposure to the deficient factor by prophylaxis at higher age. No data on haemophilia B (HB) has ever been reported. AIM: The ADVANCE Working Group investigated the incidence of late-onset inhibitors and the use of prophylaxis in patients with HA and HB aged ≥40 years. METHODS: A retrospective, observational, cohort, survey-based study of all patients aged ≥40 years with HA or HB treated at an ADVANCE HTC. RESULTS: Information on 3,095 people aged ≥40 years with HA or HB was collected. Of the 2,562 patients with severe HA, the majority (73% across all age groups) received prophylaxis. In patients with severe HA, the inhibitor incidence per 1,000 treatment years was 2.37 (age 40-49), 1.25 (age 50-59) and 1.45 (age 60+). Overall, the inhibitor incidence was greatest in those with moderate HA (5.77 (age 40-49), 6.59 (age 50-59) and 4.69 (age 60+) and the majority of inhibitor cases were preceded by a potential immune system challenge. No inhibitors in patients with haemophilia B were reported. CONCLUSION: Our data do not identify a second peak of inhibitor development in older patients with haemophilia. Prophylaxis may be beneficial in older patients with severe, and possibly moderate HA, to retain a tolerant state at higher age.

The mainstay of hemophilia treatment is to prevent bleeding through regular long-term prophylaxis and to control acute breakthrough bleeds. Various treatment options are currently available for prophylaxis, and treatment decision-making is a challenging and multifaceted process of identifying the most appropriate option for each patient. A multidisciplinary expert panel convened to develop a practical, patient-oriented algorithm to facilitate shared treatment decision-making between clinicians and patients. Key variables were identified, and an algorithm proposed based on five variables: bleeding phenotype, musculoskeletal status, treatment adherence, venous access, and lifestyle. A complementary, patient-focused preference tool was also hypothesized, with the aim of exploring individual patients' priorities, preferences, and goals. It is hoped that the proposed algorithm and the hypothesized patient preference tool will assist in selecting a treatment for each patient that is as efficient as possible in preventing bleeds while also accounting for the patient's expectations and priorities.

Arterial switch operation (ASO) is a complex neonatal operation in which transfer of the coronary arteries origins is the key to success. Coronary events after a successful ASO are not uncommon. We describe a rare case of a child who underwent an ASO in the neonatal period with one coronary (LAD) described as atretic left in place. At age seven, he developed myocardial ischemia due to retrograde flow with a steal phenomenon from the LAD into the pulmonary artery. The patient underwent a late LAD reimplantation. This case underscores that even very small ostia should be translocated at the time of ASO.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly performed in significant left main (LM) lesions. Left untreated, the prognosis is poor, but PCI and coronary bypass surgery (CABG) behold risks as well. Additional long-term outcome data might guide future treatment decisions. METHODS: Between 2012 and 2019, all 6783 patients who underwent LM PCI were prospectively enrolled in a national registry. Patients with prior CABG or prior LM PCI, and patients presenting in cardiogenic shock or after out-of-hospital cardiac arrest were excluded. From the remaining 5284 patients, baseline and procedural data as well as long-term survival were assessed. RESULTS: The annual rate of LM PCI increased from 422 (2.2% of PCIs) in 2012 to 868 in 2018 (3.0%). By 2018, 71% of the interventional cardiologists performed at least 1 LM PCI a year, though only 5 on average. Use of transradial access (TRA) in LM PCI increased from 20.4% in 2012 to 59.5% in 2019. All-cause mortality was 6.0% at 30 days and 18.5% at a mean follow-up of 33.5 months. Independent predictors of higher long-term mortality were older age, diabetes, multivessel disease, an urgent indication, a suboptimal angiographical result, and non-exclusive use of drug-eluting stents. TRAand higher operator and centre LM PCI experience were independent predictors of a lower long-term mortality. CONCLUSION: LM PCI is associated with high short- and long-term mortality. Use of TRA and higher expertise in LM PCI were associated with better survival.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The pathogenesis of FMD remains poorly understood, but a combination of genetic and environmental factors may be involved. The majority of FMD patients are women, but men may have a more progressive disease, especially when smoking. Besides the classical phenotype of string of beads or focal stenosis, arterial aneurysms, dissections, and tortuosity are frequent manifestations of the disease. However, the differential diagnosis of FMD is extensive and includes imaging artefacts as well as other arterial diseases. Diagnosis is based on CT-, MR-, or conventional catheter-based angiography during work-up of clinical manifestations, but clinically silent lesions may be found incidentally. Arterial hypertension and neurological symptoms are the most frequent clinical presentations, as renal and cerebrovascular arteries are the most commonly involved. However, involvement of most arteries throughout the body has been reported, resulting in a variety of clinical symptoms. The management of FMD depends on the vascular phenotype as well on the clinical picture. Ongoing FMD-related research will elaborate in depth the current progress in improved understandings of the disease's clinical manifestations, epidemiology, natural history and pathogenesis. This review is focused on the clinical management of adult FMD in daily practice.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.

No abstract available

No abstract available

BACKGROUND Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The pri- mary safety outcome was myocardial injury after noncardiac surgery, nonhemor- rhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular out- come, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confi- dence interval [CI], 0.67 to 0.87; absolute difference, −2.6 percentage points; 95% CI, −3.8 to −1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 per- centage points; 95% CI, −1.1 to 1.7; one-sided P=0.04 for noninferiority). CONCLUSIONS Among patients undergoing noncardiac surgery, the incidence of the com

No abstract available

Aortic valve and root replacements require an in-depth understanding of the aortic root and annulus. Both structures can be asymmetric at times, and this needs to be recognized and taken into consideration when performing valve-sparing operations or other root-replacement procedures. Moreover, the geometry of the aortic annulus can be altered, and when performing an aortic root replacement this can distort the geometry of a neoaortic valve for instance, and lead to valve dysfunction, which is difficult to reverse. We are describing an altered aortic annulus, which required modification through annulus elevation before proceeding with aortic root replacement with a graft-reinforced pulmonary-autograft.

Randomized clinical trials demonstrated transcatheter edge-to-edge repair (TEER) efficacy in improving outcome vs. medical management for functional mitral regurgitation, but limited randomized data are available for the treatment of degenerative mitral regurgitation (DMR). We aimed to compare the outcome of older patients treated with TEER vs. unoperated DMR.

Two decades of basic research and several recent clinical trials have turned the long-awaited hope of gene therapy for haemophilia into a reality. The principle is to endow liver cells with the ability to produce clotting factor VIII (FVIII) or IX (FIX), whose genetically induced defect in synthesis characterises haemophilia A and B respectively. The aim is to induce sufficient endogenous production of these clotting factors in the long term, thereby ensuring that no haemorrhages occur, particularly in the joints. [...]

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.

Numerous risk factors have been involved in the pathogenesis of hypertension. The contribution of psychological factors, including post-traumatic stress disorder, remains largely underexplored, despite their potential role in hypertension. We compared the prevalence of trauma, post-traumatic stress and other psychological disorders between hypertensive and normotensive patients from Bukavu (Democratic Republic of Congo), a 25-year war-exposed city. In this case-control study, we assessed past traumatic events with the Stressful-Events-Scale, post-traumatic stress disorder through the post-traumatic diagnostic scale, depression and alcohol use disorder through the MINI-International-Neuropsychiatric-Interview, and emotion regulation through the Emotion-Regulation-Questionnaire in 106 hypertensive and 106 normotensive patients, enrolled at the Bukavu General Hospital. Compared with normotensive controls (73% women, age: 43 ± 14 years, BP: 121 ± 10/75 ± 8 mmHg), hypertensive patients (57% women, age: 42 ± 13 years, BP: 141 ± 12/82 ± 7 mmHg, on a median of two antihypertensive drugs) were exposed to more man-made traumas (61 vs. 13%, P < 0.001), used more expressive suppression (P = 0.05) and less cognitive reappraisal (P = 0.02) as emotional regulation strategies. They developed more frequent post-traumatic stress disorder (36 vs. 7%, P < 0.001) and major depressive disorder (37 vs. 13%, P = 0.001), often in association with alcohol use disorder (23 vs. 4%, P < 0.001). In multivariate logistic regression, post-traumatic stress disorder [OR = 3.52 (1.23-6.54)], man-made trauma [OR = 2.24 (1.15-4.12)], family history of hypertension [OR = 2.24 (1.06-4.44)], fasting blood glucose [OR = 1.85 (1.07-3.08)], BMI [OR = 1.28 (1.12-2.92)], expressive suppression [OR = 1.23 (1.11-2.23)] and cognitive reappraisal [OR = 0.76 (0.63-0.98)] were independent predictors of hypertension. In Congolese populations exposed to war, man-made trauma exposure and post-traumatic stress disorder

No abstract available

New treatment possibilities and modalities are now available globally for patients with haemophilia requiring surgery or invasive procedures. The first is the appropriate application of low-dose protocols of clotting factor concentrates (CFC) achieving adequate perioperative haemostasis in resources constraint environments. The increasing availability of CFC through humanitarian aid programs allows more invasive surgeries to be performed for which efficacy and safety data should be more widely collected and reported. Second, extended half-life CFC that are increasingly available in many countries represent valuable alternatives to standard half-life products in surgical patients allowing reduced number of infusions and lower consumption, in particular for extended half-life factor IX. Third, in the era of recently introduced nonfactor prophylaxis, some minor surgical procedures can now be performed without additional haemostatic treatment, others with few low-dose administrations of CFC or bypassing agents. Additional factor VIII/IX or recombinant activated factor VII has proven to be safe and effective in association with emicizumab for major surgeries and it was effectively given at low doses in association with fitusiran (including activated prothrombin complex concentrate). No thrombotic complications have been reported in the surgical setting so far. A multidisciplinary team/facility remains crucial to manage major surgery in patients on prophylaxis with these new agents.

Background:We report the clinical and echocardiographic results of our experiencein robotic mitral valve repair over a 7‐year period. The outcomes of the earliest andthe latest patients will be compared.Methods:Between March 2012 and October 2019, 226 patients underwent roboticmitral valve repair for severe mitral regurgitation in a single institution. The first113 patients (Group 1) were operated between March 2012 and September 2015and the last 113 patients (Group 2) between October 2015 and October 2019.Conventional techniques employed in open surgery were used. Clinical andechographic follow‐up were 96.0% and 94.2% complete, respectively.Results:Successful mitral repair was achieved in all cases with no hospital mortality.The overall survival rate was 92.7 ± 2.8% and 91.0 ± 3.2% at 3 and 7 years, respec-tively, with no in between groups difference (p= 0.513). The overall freedom frommitral reoperation was 97.4 ± 1.2% at 3 and 7 years and was similar in both groups(p= 0.276). Freedom from mitral regurgitation Grade 2+ at 3 and 7 years were89.1 ± 2.6% and 87.9 ± 2.8%, respectively, with no significant difference betweengroups (p= 0.056).Conclusions:Developing a robotic mitral repair program can be done withoutcompromising the safety and efficacy of repair. After a well‐conducted training,robotic approach allows to perform simple and complex mitral repair using similartechniques as in conventional approach and without additional risk for the patient

No abstract available

no abstract available

no abstract available

Background: LDS is an autosomal dominant connective tissue disease. It is a rare multi-systemic disorder with serious vascular impact. Case report: We report a case of a 38-year-old male with Loeys-Dietz syndrome (LDS) suffering from major aortic complications. The disease initially manifested itself as a type A aortic dissection, successfully treated by open ascending aorta replacement. Ten days later, the patient developed an uncomplicated type B dissection. During follow up, the patient became symptomatic in both legs (rest pain) due to major true lumen compression. A thoracic endovascular aortic repair was performed with immediate improvement of the symptoms. During follow up, a computer tomography angiogram, showed a persistence false lumen perfusion and an aortic diameter increase. Multiple additional endovascular procedures and a final open thoracoabdominal aortic replacement were needed to exclude completely the false lumen. Conclusion: Open surgical repair is still the gold standard therapy for patients with connective tissue disease. However, with the nowadays progress, hybrid procedures could be a better option.

INTRODUCTION: In early 2021, the European Collaborative Haemophilia Network (ECHN) conducted a survey to determine whether the paradigms of care across the European region have changed with the introduction of novel therapies for people with hemophilia. METHODS: We conducted a survey in 19 ECHN centers from 17 countries in the European region. The aim was to track recent changes in the hemophilia treatment landscape, determine the impact of these changes on hemophilia treatment centers and comprehensive care centers in the region, and to look into the future of care as applied to people with hemophilia. The survey was structured to include three key areas: demographics and organization; current challenges and opportunities; and future directions. DISCUSSION: Our survey provides a snapshot of the current approach to hemophilia treatment that highlights a move toward preventive, rather than reactive care, but that also raises a number of key concerns related to costs and accessibility (particularly as related to novel therapies), time limitations for clinical research, and ongoing issues regarding human resources (particularly in terms of new doctors entering the field) and availability of laboratory resources as the use of novel therapies (some with unique modes of action and unusual adverse events, some with specialized monitoring requirements) becomes commonplace. CONCLUSION: While our survey suggests that specialized care will continue to play a central role in the management of hemophilia, the standards and protocols, as well as the centers themselves, will have to continue to evolve if they are to continue to provide the highest level of care. To meet this requirement, there is a clear need for engaging, ongoing education programs for healthcare professionals working in the field of hemophilia that can be adjusted to the changing landscape of hemophilia therapy and monitoring.

Hemophilia B is a bleeding disorder caused by a deficiency of coagulation factor IX (FIX). Treatment with FIX replacement products can increase FIX activity levels to minimize or prevent bleeding events. However, frequent dosing with standard-acting FIX products can create a high treatment burden. Long-acting products have been developed to maintain bleed protection with extended dosing intervals. Recombinant factor IX-albumin fusion protein (rIX-FP) is a long-acting product indicated for the treatment and prophylaxis of bleeding events and perioperative management in adult and pediatric patients. This review outlines data from all previously treated patients in the Prophylaxis and On-Demand Treatment using Longer Half-Life rIX-FP (PROLONG-9FP) clinical trial program and summarizes real-world data evaluating the use of rIX-FP in routine clinical practice. In the PROLONG-9FP program, rIX-FP demonstrated effective hemostasis in all patients at dose regimens of up to 21 days in patients aged ≥ 18 years and up to 14 days in patients aged < 12 years. rIX-FP has a favorable pharmacokinetic profile and an excellent safety and tolerability profile. Extended dosing intervals with rIX-FP led to high levels of adherence and reduced consumption compared with other FIX therapies. Data from real-world practice are encouraging and reflect the results of the clinical trials.

Haemophilia B is a rare X-linked genetic deficiency of coagulation factor IX (FIX) that, if untreated, can cause recurrent and disabling bleeding, potentially leading to severe arthropathy and/or life-threatening haemorrhage. Recent decades have brought significant improvements in haemophilia B management, including the advent of recombinant FIX and extended half-life FIX. This therapeutic landscape continues to evolve with several non-factor replacement therapies and gene therapies under investigation. Given the rarity of haemophilia B, the evidence base and clinical experience on which to establish clinical guidelines are relatively sparse and are further challenged by features that are distinct from haemophilia A, precluding extrapolation of existing haemophilia A guidelines. Due to the paucity of formal haemophilia B-specific clinical guidance, an international Author Group was convened to develop a clinical practice framework. The group comprised 15 haematology specialists from Europe, Australia, Japan, Latin America and North America, covering adult and paediatric haematology, laboratory medicine and biomedical science. A hybrid approach combining a systematic review of haemophilia B literature with discussion of clinical experience utilized a modified Delphi format to develop a comprehensive set of clinical recommendations. This approach resulted in 29 recommendations for the clinical management of haemophilia B across five topics, including product treatment choice, therapeutic agent laboratory monitoring, pharmacokinetics considerations, inhibitor management and preparing for gene therapy. It is anticipated that this clinical practice framework will complement existing guidelines in the management of people with haemophilia B in routine clinical practice and could be adapted and applied across different regions and countries.

Aims Purpose of this study is to compare the clinical course and outcome of patients with recurrent versus first-episode infective endocarditis (IE). Methods Patients with recurrent and first-episode IE enrolled in the EUROpean ENDOcarditis (EURO-ENDO) registry including 156 centres were identified and compared using propensity score matching. Recurrent IE was classified as relapse when IE occurred ≤6 months after a previous episode or reinfection when IE occurred >6 months after the prior episode. Results 3106 patients were enrolled: 2839 (91.4%) patients with first-episode IE (mean age 59.4 (±18.1); 68.3% male) and 267 (8.6%) patients with recurrent IE (mean age 58.1 (±17.7); 74.9% male). Among patients with recurrent IE, 13.2% were intravenous drug users (IVDUs), 66.4% had a repaired or replaced valve with the tricuspid valve being more frequently involved compared with patients with first-episode IE (20.3% vs 14.1%; p=0.012). In patients with a first episode of IE, the aortic valve was more frequently involved (45.6% vs 39.5%; p=0.061). Recurrent relapse and reinfection were 20.6% and 79.4%, respectively. Staphylococcus aureus was the microorganism most frequently observed in both groups (p=0.207). There were no differences in in-hospital and post-hospitalisation mortality between recurrent and first-episode IE. In patients with recurrent IE, in-hospital mortality was higher in IVDU patients. Independent predictors of poorer in-hospital and 1-year outcome, including the occurrence of cardiogenic and septic shock, valvular disease severity and failure to undertake surgery when indicated, were similar for recurrent and first-episode IE. Conclusions In-hospital and 1-year mortality was similar in patients with recurrent and first-episode IE who shared similar predictors of poor outcome.

Background: There has been growing evidence of the benefits of high-intensity aerobic interval training (HIIT) and resistance training (RES) for populations with cancer. However, these two modalities have not yet been performed alone in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (NACRT). Therefore, this study aimed to determine the feasibility of HIIT and RES in rectal cancer patients undergoing NACRT. Materials and methods: Rectal cancer patients set to undergo NACRT were randomly assigned to HIIT intervention, RES intervention, or the usual care. Feasibility of HIIT and RES was assessed by measuring recruitment rate, adherence (retention rate, attendance rate, and exercise sessions duration and intensity), and adverse events. Endpoints (changes in fatigue, health-related quality of life, depression, daytime sleepiness, insomnia, sleep quality, functional exercise capacity, and executive function) were assessed at baseline and at week 5. Results: Among the 20 eligible patients, 18 subjects were enrolled and completed the study, yielding a 90% recruitment rate and 100% retention rate. Attendance at exercise sessions was excellent, with 92% in HIIT and 88% in RES. No exercise-related adverse events occurred. Conclusion: This study demonstrated that HIIT and RES are feasible in rectal cancer patients undergoing NACRT.

This review compares the methodology of published clinical studies investigating the extended-half-life (EHL) factor VIII (FVIII) products, rFVIIIFc (efmoroctocog alfa, Elocta®/Eloctate®), BAY 94-9027 (damoctocog alfa pegol, Jivi®), BAX 855 (rurioctocog alfa pegol, Adynovate®) and N8-GP (turoctocog alfa pegol, Esperoct®) including the phase 2/3 studies, A-LONG (NCT01181128), PROTECT VIII (NCT01580293), PROLONG-ATE (NCT01736475) and pathfinder2 (NCT01480180), respectively, and their corresponding pediatric studies and extensions. Study results are interpreted from a treating physician's perspective, translating into evidence-based, real-life use of the different EHL recombinant FVIII products for personalized prophylaxis. The similarities between the studies include methodology, objectives, study design and cohort size. The differences include duration, prophylactic dosing intervals, number of patient arms, use of control group and randomization, and treatment allocation. Comparing these studies broadens physicians' understanding of each treatment's applicability. Further evaluation of study data and future real-world studies should help physicians to confidently individualize and select treatment for each patient.

Inhibitors of sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown effective glucose-lowering effects associated with improved clinical outcomes in diabetic patients and heart failure patients. As SGLT2 inhibitors can increase phosphate levels, they can also modulate FGF-23 production, a hormone directly involved in regulation of bone and mineral metabolism, but also a strong predictor of adverse cardiovascular events. We therefore discuss the relevance of FGF-23 as a companion testing of SGLT2 treatment, in addition to standard clinical biology tests.