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Background: Patient reported outcomes (PROs) are important measures in acquired heart disease but have not been well defined in Adult Congenital Heart Disease (ACHD). Our aim was to explore the discriminatory capacity of PRO survey tools in Fontan circulatory failure (FCF). Methods: Consecutive adults were enrolled from our ambulatory clinics. Inclusion criteria were age ≥18 years, a Fontan circulation or a hemodynamically insignificant shunt lesion, and sufficient cognitive/language abilities to complete PROs. A comprehensive package of PRO measures, designed to assess perceived health-related quality of life (HRQOL) was administered (including the Kansas City Cardiomyopathy Questionnaire [KCCQ-12], EuroQol-5-dimension [EQ5D], Short Form Health Status Survey [SF-12], self-reported New York Heart Association [NYHA] Functional Class, and Specific Activity Scale [SAS]). Results: We compared 54 Fontan patients (35 ± 10 years) to 25 simple shunt lesion patients (34 ± 11 years). The KCCQ-12 score was lower in Fontan versus shunt lesion patients (87 [IQR 79, 95] versus 100 [IQR 97, 100], p-value < 0.001). The FCF subgroup was associated with lower KCCQ-12 scores as compared with the non-FCF subgroup (82 [IQR 56, 89] versus 93 [IQR 81, 98], p-value = 0.002). Although the KCCQ-12 had the best discriminatory capacity for determination of FCF of all PRO tools studied (c-statistic 0.75 [CI 0.62, 0.88]), superior FCF discrimination was achieved when the KCCQ-12 was combined with all PRO tools (c-statistic 0.82 [CI 0.71, 0.93]). Conclusions: The KCCQ-12 questionnaire demonstrated good discriminatory capacity for the identification of FCF, which was further improved through the addition of complementary PRO tools. Further research will establish the value of PRO tools to guide management strategies in ACHD.
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BACKGROUND: Little is known about the procedural characteristics, case volumes, and mortality rates for early- vs non-early-career interventional cardiologists in the United States. OBJECTIVES: This study examined operator-level data for patients who underwent percutaneous coronary intervention (PCI) between April 2018 and June 2022. METHODS: Data were collected from the National Cardiovascular Data Registry CathPCI Registry, American Board of Internal Medicine certification database, and National Plan and Provider Enumeration System database. Early-career operators were within 5 years of the end of training. Annual case volume, expected mortality and bleeding risk, and observed/predicted mortality and bleeding outcomes were evaluated. RESULTS: A total of 1,451 operators were early career; 1,011 changed their career status during the study; and 6,251 were non-early career. Overall, 514,540 patients were treated by early-career and 2,296,576 patients by non-early-career operators. The median annual case volume per operator was 59 (Q1-Q3: 31-97) for early-career and 57 (Q1-Q3: 28-100) for non-early-career operators. Early-career operators were more likely to treat patients presenting with ST-segment elevation myocardial infarction and urgent indications for PCI (both P < 0.001). The median predicted mortality risk was 2.0% (Q1-Q3: 1.5%-2.7%) for early-career and 1.8% (Q1-Q3: 1.2%-2.4%) for non-early-career operators. The median predicted bleeding risk was 4.9% (Q1-Q3: 4.2%-5.7%) for early-career and 4.4% (Q1-Q3: 3.7%-5.3%) for non-early-career operators. After adjustment, an increased risk of mortality (OR: 1.08; 95% CI: 1.05-1.17; P < 0.0001) and bleeding (OR: 1.08; 95% CI: 1.05-1.12; P < 0.0001) were associated with early-career status. CONCLUSIONS: Early-career operators are caring for patients with more acute presentations and higher predicted risk of mortality and bleeding compared with more experienced colleagues, with modestly worse outcomes. These data should inform institutional practices to support the development of early-career proceduralists.
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Cardiólogos , Intervención Coronaria Percutánea , Sistema de Registros , Humanos , Estados Unidos/epidemiología , Intervención Coronaria Percutánea/estadística & datos numéricos , Femenino , Masculino , Persona de Mediana Edad , Cardiólogos/estadística & datos numéricos , Anciano , Competencia ClínicaRESUMEN
Depression commonly co-occurs with chronic pain and can worsen pain outcomes. Recent theoretical work has hypothesized that pain localized to the left hemibody is a risk factor for worse depression due to overlap in underlying neural substrates. This hypothesis has not been tested a priori. Using a large sample of treatment-seeking adults with mixed-etiology chronic pain (N = 1,185), our cross-sectional study tested whether patients with left-sided pain endorse worse depressive symptoms. We also examined differences in other pain-related functioning measures. We tested 4 comparisons based on painful body areas using the CHOIR body map: 1) only left-sided (OL) versus any right-sided pain; 2) only right-sided (OR) versus any left-sided pain; 3) OL versus OR versus bilateral pain; and 4) more left-sided versus more right-sided versus equal-sided pain. Analysis of variance models showed OL pain was not associated with worse depression (F = 5.50, P = .019). Any left-sided pain was associated with worse depression, though the effect was small (F = 8.58, P = .003, Cohens d = .29). Bilateral pain was associated with worse depression (F = 8.05, P < .001, Cohens d = .24-.33). Regardless of pain location, more body areas endorsed was associated with greater depression. Although a more rigorous assessment of pain laterality is needed, our findings do not support the hypothesis that left-lateralized pain is associated with worse depression. PERSPECTIVE: Pain lateralized to the left side of the body has been hypothesized as a risk factor for worse depression in chronic pain, despite never being tested in a large, real-world sample of patients with chronic pain. Findings showed that more widespread pain, not pain laterality, was associated with worse depression.
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BACKGROUND: Left ventricular assist device (LVAD) support offers remodeling potential in some patients. Our goal was to use noninvasively derived pressure-volume (PV) loops to understand the effect of demographic and device variables on serial changes in cardiac function under pump support. METHODS: Thirty-two consecutive Medtronic HeartWare Ventricular Assist Device (HVAD) patients (mean 55.9 ± 12.3 years, 81.3% male) were prospectively recruited. Single-cycle ventricular pressure and volume were estimated using a validated algorithm. PV loops (n = 77) and corresponding cardiac chamber dynamics were derived at predefined postimplant timepoints (1, 3, 6 months). Changes in PV loop parameters sustained across the 6-month period were characterized using mixed-effects modeling. The influence of demographic and device variables on the observed changes was assessed. RESULTS: Across a 6-month period, the mean ventricular function parameters remained stable. Significant predictors of monthly improvement of stroke work include: lower pump speeds (2400 rpm vs 2500-2800 rpm) [0.0.051 mm Hg/liter/month (p = 0.001)], high pulsatility index (>1.0 vs <1.0) [0.052 mm Hg/liter/month (p = 0.012)], and ischemic cardiomyopathy indication for LVAD implantation (vs nonischemic) [0.0387 mm Hg/liter/month (p = 0.007)]. Various other cardiac chamber function parameters including cardiac power, peak systolic pressure, and LV elastance also showed improvements in these cohorts. CONCLUSIONS: Factors associated with improvement in ventricular energetics and hemodynamics under LVAD support can be determined with noninvasive PV loops. Understanding the basis of increasing ventricular load to optimize myocardial remodeling may prove valuable in selecting eligible recovery candidates.
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Corazón Auxiliar , Función Ventricular Izquierda , Humanos , Masculino , Femenino , Miocardio , Ventrículos Cardíacos , Hemodinámica/fisiologíaRESUMEN
BACKGROUND: Current guidelines recommend initial monotherapy for pulmonary arterial hypertension (PAH) with cardiopulmonary comorbidities, despite limited available evidence to guide management. RESEARCH QUESTION: Do left heart disease (LHD) risk factors have an impact on treatment response and influence applicability of risk assessment in a real-world cohort of patients with PAH? STUDY DESIGN AND METHODS: The Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) trial criteria was used to define the phenotype of patients with PAH with risk factors for LHD. Treatment strategy, functional outcome, long-term survival, and risk discrimination were compared with a reference PAH cohort using the Pulmonary Hypertension Society of Australia and New Zealand Registry. RESULTS: A total of 487 incident patients with PAH diagnosed between 2011 and 2020 were included. Of these, 103 (21.1%) fulfilled the definition of PAH with LHD risk factors, with 384 (78.9%) remaining as the reference group. Patients in the PAH with LHD risk factors group were older (66 ± 13 vs 58 ± 19 years; P < .001), had lower pulmonary vascular resistance (393 ± 266 vs 708 ± 391 dyn.s/cm5; P = .031), and had worse 6-min walk distance (286 ± 130 vs 327 ± 136 m; P = .005) at diagnosis. The PAH with LHD risk factors group was less likely to receive initial combination therapy (27% vs 44%; P = .02). Changes in 6-min walk distance at 12 months were similar in both groups (43 ± 77 m in the PAH with LHD risk factors group and 50 ± 90 m in the reference group; P = .50), including when stratified by initial treatment strategy (PAH with LHD risk factors group vs reference PAH group: monotherapy: 40 ± 81 vs 38 ± 95 m, P = .87; combination therapy: 53 ± 78 vs 64 ± 106 m, P = .511). Functional class improvements were also similar in both groups. REVEAL Registry 2.0 risk score effectively discriminated risk in both populations (C statistic = 0.756 for the PAH with LHD risk factors group and C statistic = 0.750 for the reference PAH group). There was no difference in survival between the two groups (log-rank test, P = .29). INTERPRETATION: In a real-world cohort, patients with PAH with LHD risk factors were less likely to be exposed to initial combination therapy. Nevertheless, selected patients with PAH with LHD risk factors who were treated with initial combination therapy derived similar functional response compared with the reference group. Further studies are needed to phenotype patients with PAH with cardiopulmonary comorbidities who may benefit from initial combination therapy.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Quimioterapia Combinada , Tadalafilo/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar Primaria Familiar/complicaciones , Factores de Riesgo de Enfermedad CardiacaRESUMEN
AIMS: There is limited data describing major adverse kidney events (MAKE) in patients supported with ventricular assist devices (VAD). We aim to describe the association between MAKE and survival, risk factors for MAKE, and renal trajectory in VAD supported patients. METHODS AND RESULTS: We conducted a single-centre retrospective analysis of consecutive VAD implants between 2010 and 2019. Baseline demographics, biochemistry, and adverse events were collected for the duration of VAD support. MAKE was defined as the first event to occur of sustained drop (>50%) in estimated glomerular filtration rate (eGFR), progression to stage V chronic kidney disease, initiation or continuation of renal replacement therapy beyond implant admission or death on renal replacement therapy at any time. One-hundred and seventy-three patients were included, median age 56.8 years, 18.5% female, INTERMACS profile 1 or 2 in 75.1%. Thirty-seven patients experienced MAKE. On multivariate analysis, post-implant clinical right ventricular failure and the presence of chronic haemolysis, defined by the presence of schistocytes on blood film analysis, were significantly associated with increased risk of MAKE (adjusted odds ratio 9.88, P < 0.001 and adjusted odds ratio 3.33, P = 0.006, respectively). MAKE was associated with reduced survival (hazard ratio 4.80, P < 0.001). Patients who died or experienced MAKE did not demonstrate the expected transient 3-month improvement in eGFR, seen in other cohorts. CONCLUSIONS: MAKE significantly impacts survival. In our cohort, MAKE was predicted by post-implant right ventricular failure and chronic haemolysis. The lack of early eGFR improvement on VAD support may indicate higher risk for MAKE.
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Insuficiencia Cardíaca , Corazón Auxiliar , Humanos , Femenino , Persona de Mediana Edad , Masculino , Corazón Auxiliar/efectos adversos , Estudios Retrospectivos , Hemólisis , RiñónRESUMEN
For decades, it was considered that plasma kallikrein's (PKa) sole function within the coagulation cascade is the activation of factor (F)XII. Until recently, the two key known activators of FIX within the coagulation cascade were activated FXI(a) and the tissue factor-FVII(a) complex. Simultaneously, and using independent experimental approaches, three groups identified a new branch of the coagulation cascade, whereby PKa can directly activate FIX. These key studies identified that (1) FIX or FIXa can bind with high affinity to either prekallikrein (PK) or PKa; (2) in human plasma, PKa can dose dependently trigger thrombin generation and clot formation independent of FXI; (3) in FXI knockout murine models treated with intrinsic pathway agonists, PKa activity results in increased formation of FIXa:AT complexes, indicating direct activation of FIX by PKa in vivo. These findings suggest that there is both a canonical (FXIa-dependent) and non-canonical (PKa-dependent) pathway of FIX activation. These three recent studies are described within this review, alongside historical data that hinted at the existence of this novel role of PKa as a coagulation clotting factor. The implications of direct PKa cleavage of FIX remain to be determined physiologically, pathophysiologically, and in the context of next-generation anticoagulants in development.
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It is of increasing importance to understand and predict changes to the systemic and pulmonary circulations in pulmonary hypertension (PH). To do so, it is necessary to describe the circulation in complete quantitative terms. Characteristic impedance (Zc) expresses opposition of the circulation to pulsatile blood flow. Evaluation of systemic and pulmonary Zc relationships according to PH classification has not previously been described. Prospective study of 40 clinically indicated patients referred for CMR and RHC (56 ± 18 years; 70% females, eight mPAP ≤ 25 mmHg, 16 pre-capillary [Pre-cPH], eight combined pre- and post-capillary [Cpc-PH] and eight isolated left-heart disease [Ipc-PH]). CMR provided assessment of ascending aortic (Ao) and pulmonary arterial (PA) flow, and RHC, central Ao and PA pressure. Systemic and pulmonary Zc were expressed as the relationship of pressure to flow in the frequency domain. Baseline demographic characteristics were well-matched across PH subclasses. In those with a mPAP ≤25mHg, systemic Zc and SVR were >2 times higher than pulmonary Zc and PVR. Only Pre-cPH was associated with inverse pulsatile (systemic Zc 58 [45-69] vs pulmonary Zc 70 [58-85]), but not steady-state (SVR 1101 [986-1752] vs. PVR 483 [409-557]) relationships. Patients with CpcPH and IpcPH had concordant pulsatile and steady-state relationships (Graphical Abstract). Measurement of, and the relationship between, systemic and pulmonary Zc in patients according to PH sub-classification has not previously been described. Systemic Zc was routinely higher than pulmonary Zc, except in patients with newly diagnosed Pre-cPH, where inverse pulsatile but not steady-state relationships were observed.
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Hipertensión Pulmonar , Femenino , Humanos , Masculino , Estudios Prospectivos , Hemodinámica/fisiología , Corazón , Circulación Pulmonar , Resistencia VascularRESUMEN
BACKGROUND: The effect of pulmonary hypertension (PH) on right ventricular (RV) afterload is commonly defined by elevation of pulmonary artery (PA) pressure or pulmonary vascular resistance (PVR). In humans however, one-third to half of the hydraulic power in the PA is contained in pulsatile components of flow. Pulmonary impedance (Zc) expresses opposition of the PA to pulsatile blood flow. We evaluate pulmonary Zc relationships according to PH classification using a cardiac magnetic resonance (CMR)/right heart catheterization (RHC) method. METHODS: Prospective study of 70 clinically indicated patients referred for same-day CMR and RHC [60 ± 16 years; 77% females, 16 mPAP <25 mmHg (PVR <240 dynes.s.cm-5 /mPCWP <15 mmHg), 24 pre-capillary (PrecPH), 15 isolated post-capillary (IpcPH), 15 combined pre-capillary/post-capillary (CpcPH)]. CMR provided assessment of PA flow, and RHC, central PA pressure. Pulmonary Zc was expressed as the relationship of PA pressure to flow in the frequency domain (dynes.s.cm-5 ). RESULTS: Baseline demographic characteristics were well matched. There was a significant difference in mPAP (P < 0.001), PVR (P = 0.001), and pulmonary Zc between mPAP<25 mmHg patients and those with PH (mPAP <25 mmHg: 47 ± 19 dynes.s.cm-5 ; PrecPH 86 ± 20 dynes.s.cm-5 ; IpcPH 66 ± 30 dynes.s.cm-5 ; CpcPH 86 ± 39 dynes.s.cm-5 ; P = 0.05). For all patients with PH, elevated mPAP was found to be associated with raised PVR (P < 0.001) but not with pulmonary Zc (P = 0.87), except for those with PrecPH (P < 0.001). Elevated pulmonary Zc was associated with reduced RVSWI, RVEF, and CO (all P < 0.05), whereas PVR and mPAP were not. CONCLUSIONS: Raised pulmonary Zc was independent of elevated mPAP in patients with PH and more strongly predictive of maladaptive RV remodelling than PVR and mPAP. Use of this straightforward method to determine pulmonary Zc may help to better characterize pulsatile components of RV afterload in patients with PH than mPAP or PVR alone.
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Hipertensión Pulmonar , Disfunción Ventricular Derecha , Femenino , Humanos , Masculino , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico , Pronóstico , Disfunción Ventricular Derecha/diagnóstico , Disfunción Ventricular Derecha/etiología , Estudios Prospectivos , Impedancia EléctricaRESUMEN
Tetralogy of Fallot is a cyanotic congenital heart disease, for which various surgical techniques allow patients to survive to adulthood. Currently, the natural history of corrected tetralogy of Fallot is underlined by progressive right ventricular (RV) failure due to pulmonic regurgitation and other residual lesions. The underlying cellular mechanisms that lead to RV failure from chronic volume overload are characterized by microvascular and mitochondrial dysfunction through various regulatory molecules. On a clinical level, these cardiac alterations are commonly manifested as exercise intolerance. The degree of exercise intolerance can be objectified and aid in prognostication through cardiopulmonary exercise testing. The timing for reintervention on residual lesions contributing to RV volume overload remains controversial; however, interval assessment of cardiac function and volumes by echocardiography and magnetic resonance imaging may be helpful. In patients who develop clinically important RV failure, clinicians should aim to maintain a euvolemic state through the use of diuretics while paying particular attention to preload and kidney function. In patients who develop signs of cardiogenic shock from right heart failure, stabilization through the use of inotropes and pressor is indicated. In special circumstances, the use of mechanical support may be appropriate. However, cardiologists should pay particular attention to residual lesions that may impact the efficacy of the selected device.
De nombreuses techniques chirurgicales permettent aux patients présentant une tétralogie de Fallot (TF), une forme de cardiopathie congénitale, de survivre jusqu'à l'âge adulte. À l'heure actuelle, l'évolution naturelle de la TF corrigée est caractérisée par une insuffisance ventriculaire droite (VD) progressive attribuable à une régurgitation pulmonaire et à d'autres lésions résiduelles. Les mécanismes cellulaires sous-jacents qui mènent à l'insuffisance VD due à une surcharge volumique chronique sont caractérisés par une dysfonction microvasculaire et mitochondriale faisant intervenir diverses molécules régulatrices. Sur le plan clinique, ces atteintes cardiaques se manifestent par une intolérance à l'effort qui peut être évaluée au moyen d'une épreuve d'effort cardiorespiratoire, ce qui permet de faciliter l'établissement d'un pronostic. Le moment propice pour une réintervention en cas de lésions résiduelles contribuant à la surcharge volumique du ventricule droit demeure controversé; toutefois, il peut être utile d'évaluer régulièrement la fonction et les volumes cardiaques au moyen d'une échocardiographie et de tests d'imagerie par résonance magnétique. En présence d'une insuffisance VD cliniquement importante, les cliniciens doivent tenter de maintenir les patients dans un état euvolémique en utilisant des diurétiques, tout en accordant une attention particulière à la précharge et à la fonction rénale. Si les patients manifestent des signes de choc cardiogénique associé à une insuffisance cardiaque droite, il convient de leur administrer des inotropes et des vasopresseurs pour stabiliser leur état. Dans certains cas, l'utilisation d'un dispositif d'assistance mécanique peut être appropriée. Cependant, les cardiologues doivent être attentifs aux lésions résiduelles, car elles peuvent influencer l'efficacité de ce dispositif.
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BACKGROUND: Fibrinogen is an abundant plasma protein with an essential role in blood coagulation and haemostasis thus receiving significant research interest. However, protein purification is time consuming and commercial preparations often have protein contaminants. The aim of this study was to develop a new method to purify high quality and functional fibrinogen. METHODS: Fibrinogen-specific Affimer protein, isolated using phage display systems, was immobilised to SulfoLink resin column and employed for fibrinogen purification from plasma samples. Fibrinogen was eluted using a high pH solution. Commercial human fibrinogen was also further purified using the Affimer column. Fibrinogen purity was determined by SDS-PAGE and mass spectrometry, while functionality was assessed using turbidimetric analysis. RESULTS: Affimer-purified fibrinogen from human plasma showed purity at least comparable to commercially available preparations and was able to form physiological fibrin networks. Further purification of commercially available fibrinogen using the Affimercolumn eliminated multiple contaminant proteins, a significant number of which are key elements of the coagulation cascade, including plasminogen and factor XIII. CONCLUSIONS: The Affimercolumn represents a proof of concept novel, rapid method for isolating functional fibrinogen from plasma and for further purification of commercially available fibrinogen preparations. GENERAL SIGNIFICANCE: Our methodology provides an efficient way of purifying functional fibrinogen with superior purity without the need of expensive pieces of equipment or the use of harsh conditions.
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Fibrina , Fibrinógeno , Cromatografía de Afinidad/métodos , Fibrina/metabolismo , Fibrinógeno/metabolismo , Hemostasis , Humanos , PlasminógenoRESUMEN
Fibrinogen, one of the most abundant plasma proteins playing a key role in hemostasis, is an important modulator of wound healing and host defense against microbes. In the current review, we address the role of fibrin(ogen) throughout the process of wound healing and subsequent tissue repair. Initially fibrin(ogen) acts as a provisional matrix supporting incoming leukocytes and acting as reservoir for growth factors. It later goes on to support re-epithelialization, angiogenesis, and fibroplasia. Importantly, removal of fibrin(ogen) from the wound is essential for wound healing to progress. We also discuss how fibrin(ogen) functions through several mechanisms to protect the host against bacterial infection by providing a physical barrier, entrapment of bacteria in fibrin(ogen) networks, and by directing immune cell function. The central role of fibrin(ogen) in defense against bacterial infection has made it a target of bacterial proteins, evolved to interact with fibrin(ogen) to manipulate clot formation and degradation for the purpose of promoting microbial virulence and survival. Further understanding of the dual roles of fibrin(ogen) in wound healing and infection could provide novel means of therapy to improve recovery from surgical or chronic wounds and help to prevent infection from highly virulent bacterial strains, including those resistant to antibiotics.
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Fibrina , Fibrinógeno , Estrona/análogos & derivados , Fibrina/metabolismo , Fibrinógeno/metabolismo , Humanos , Control de Infecciones , Cicatrización de HeridasRESUMEN
PURPOSE OF THE REVIEW: The purpose of this review is to discuss the risk stratification and management of pregnancy in women with complex congenital heart disease. RECENT FINDINGS: Classifying congenital heart defects (CHD) including both anatomy and physiology is important for maternal risk stratification. Although most women with CHD can tolerate the physiological challenge of pregnancy, some may experience serious risks both to their health and that of their foetus. The WHO maternal risk classification model remains the best-validated risk measure. Ideally, women with CHD should have pre-conception assessment with a CHD cardiologist. General principles of management, such as need for expert centre delivery, a multidisciplinary team, epidural and mode of delivery are based on WHO risk in combination with expert assessment of status. CHD is increasingly prevalent in women of child-bearing age. Assessment by an adult CHD cardiologist, ideally pre-conception, is key in assessing and minimising risk to mother and foetus.
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Cardiopatías Congénitas , Insuficiencia Cardíaca , Complicaciones Cardiovasculares del Embarazo , Adulto , Femenino , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/terapia , Humanos , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Complicaciones Cardiovasculares del Embarazo/terapia , Factores de RiesgoRESUMEN
Thrombus formation remains a major cause of morbidity and mortality worldwide. Current antiplatelet and anticoagulant therapies have been effective at reducing vascular events, but at the expense of increased bleeding risk. Targeting proteins that interact with fibrinogen and which are involved in hypofibrinolysis represents a more specific approach for the development of effective and safe therapeutic agents. The antifibrinolytic proteins alpha-2 antiplasmin (α2AP), thrombin activatable fibrinolysis inhibitor (TAFI), complement C3 and plasminogen activator inhibitor-2 (PAI-2), can be incorporated into the fibrin clot by FXIIIa and affect fibrinolysis by different mechanisms. Therefore, these antifibrinolytic proteins are attractive targets for the development of novel therapeutics, both for the modulation of thrombosis risk, but also for potentially improving clot instability in bleeding disorders. This review summarises the main properties of fibrinogen-bound antifibrinolytic proteins, their effect on clot lysis and association with thrombotic or bleeding conditions. The role of these proteins in therapeutic strategies targeting the fibrinolytic system for thrombotic diseases or bleeding disorders is also discussed.
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Carboxipeptidasa B2/genética , Fibrinógeno/genética , Hemorragia/terapia , alfa 2-Antiplasmina/genética , Anticoagulantes , Complemento C3/genética , Fibrinólisis/genética , Hemorragia/genética , Humanos , Inhibidor 2 de Activador Plasminogénico/genética , Trombosis/genéticaRESUMEN
BACKGROUND AND OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious condition occurring in 2%-4% of patients after acute pulmonary embolism. Pulmonary endarterectomy (PEA) is a potential cure for technically operable disease. The epidemiology and long-term outcomes of CTEPH have not been previously described in Australia and New Zealand. METHODS: Data were extracted from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry for patients diagnosed with CTEPH between January 2004 and March 2020. Baseline characteristics, treatment strategies, outcome data and long-term survival are reported. RESULTS: A total of 386 patients were included with 146 (37.8%) undergoing PEA and 240 (62.2%) in the non-PEA group. PEA patients were younger (55 ± 16 vs. 62 ± 16 years, p < 0.001) with higher baseline 6-min walk distance (6MWD; 405 ± 122 vs. 323 ± 146 m, p = 0.021), whilst both groups had similar baseline pulmonary haemodynamics. Pulmonary hypertension-specific therapy was used in 54% of patients post-PEA and 88% in the non-PEA group. The 1-, 3- and 5-year survival rates were 93%, 87% and 84% for the PEA group compared to 86%, 73% and 62%, respectively, for the non-PEA group (p < 0.001). Multivariate survival analysis showed baseline 6MWD was an independent predictor of survival in both operated and medically managed patients. CONCLUSION: In this first multicentre report of CTEPH in Australia and New Zealand, long-term survival is comparable to that in other contemporary CTEPH registries. However, PEA was only performed in a minority of CTEPH patients (37.8%) and significantly less than overseas reports. Greater awareness of PEA and improved patient access to experienced CTEPH centres are important priorities.
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Hipertensión Pulmonar , Embolia Pulmonar , Enfermedad Crónica , Endarterectomía , Humanos , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/terapia , Nueva Zelanda/epidemiología , Arteria Pulmonar , Embolia Pulmonar/epidemiología , Embolia Pulmonar/terapia , Sistema de Registros , Resultado del TratamientoRESUMEN
BACKGROUND: End-stage Eisenmenger syndrome (ES) due to unrepaired atrial septal defect (ASD) or ventricular septal defect (VSD) is an indication for lung transplantation (LTx) or heart-lung transplantation (HLTx). Limited evidence exists as to the optimal transplant strategy for this unique population. AIM: To describe waitlist characteristics and post-transplant outcomes in patients with ES-ASD or ES-VSD. METHODS: Using the ISHLT Registry, data were extracted for all ES-ASD or ES-VSD patients who underwent transplantation between 1987 and 2018. Additional data were sought for patients listed for LTx or HLTx in the OPTN Registry during the same period. Early era was defined as 1987-2004, and current era was defined as 2005-2018. RESULTS: In the current era, patients with ES-ASD or ES-VSD represented a lessening proportion of all LTx and HLTx. Compared to LTx for other indications, the odds of transplantation were significantly less for both ES-ASD 0.18 [0.07-0.50] and ES-VSD 0.03 [0.004-0.22]. In the early era, an equivalent survival was observed for ES-ASD who underwent HLTx versus LTx (p = 0.47), and superior survival for ES-VSD (p = 0.015). In contrast, ES-ASD patients who underwent LTx from the current era displayed better survival compared with HLTx, 10-year survival 52% vs 30% p = 0.036. Similar survival were observed for ES-VSD for both transplant strategies (p = 0.68). CONCLUSION: LTx shows superior survival outcomes in the current era for ES ASD patients, and equivalent outcomes for ES-VSD. In the current era, ES-ASD or ES-VSD patients were less likely to be transplanted than other candidates for LTx.