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Rationale: von Willebrand factor (vWF) mediates platelet adhesion during thrombosis. While chronic thromboembolic pulmonary hypertension (CTEPH) is associated with increased plasma levels of vWF, the role of this protein in CTEPH has remained enigmatic. Objectives: To identify the role of vWF in CTEPH. Methods: CTEPH-specific patient plasma and pulmonary endarterectomy material from patients with CTEPH were used to study the relationship between inflammation, vWF expression, and pulmonary thrombosis. Cell culture findings were validated in human tissue, and proteomics and chromatin immunoprecipitation were used to investigate the underlying mechanism of CTEPH. Measurements and Main Results: vWF is increased in plasma and the pulmonary endothelium of CTEPH patients. In vitro, the increase in vWF gene expression and the higher release of vWF protein upon endothelial activation resulted in elevated platelet adhesion to CTEPH endothelium. Proteomic analysis revealed that nuclear factor (NF)-κB2 was significantly increased in CTEPH. We demonstrate reduced histone tri-methylation and increased histone acetylation of the vWF promoter in CTEPH endothelium, facilitating binding of NF-κB2 to the vWF promoter and driving vWF transcription. Genetic interference of NFκB2 normalized the high vWF RNA expression levels and reversed the prothrombotic phenotype observed in CTEPH-pulmonary artery endothelial cells. Conclusions: Epigenetic regulation of the vWF promoter contributes to the creation of a local environment that favors in situ thrombosis in the pulmonary arteries. It reveals a direct molecular link between inflammatory pathways and platelet adhesion in the pulmonary vascular wall, emphasizing a possible role of in situ thrombosis in the development or progression of CTEPH.
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Hipertensão Pulmonar , Fator de von Willebrand , Células Endoteliais/metabolismo , Endotélio Vascular , Epigênese Genética , Humanos , Agregação Plaquetária , Proteômica , Fator de von Willebrand/análise , Fator de von Willebrand/genética , Fator de von Willebrand/metabolismoRESUMO
Tyrosine kinase inhibitors (TKI) are known to be highly effective in the treatment of various cancers with kinase-domain mutations such as chronic myelogenous leukemia. However, they have important side effects such as increased vascular permeability and pulmonary hypertension. In patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest, these side effects may exacerbate postoperative complications such as reperfusion edema and persistent pulmonary hypertension. We report on a simple modification of the perfusion strategy to increase intravascular oncotic pressure by retrograde autologous priming and the addition of packed cells and albumin in a patient treated with a TKI.
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Neoplasias Hematológicas , Hipertensão Pulmonar , Embolia Pulmonar , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/cirurgia , Perfusão/efeitos adversos , Endarterectomia/métodos , Neoplasias Hematológicas/complicações , Embolia Pulmonar/complicaçõesRESUMO
INTRODUCTION: Pulmonary endarterectomy requires cardiopulmonary bypass and deep hypothermic circulatory arrest, which may prolong the activated clotting time. We investigated whether activated clotting time-guided anticoagulation under these circumstances suppresses hemostatic activation. METHODS: Individual heparin sensitivity was determined by the heparin dose-response test, and anticoagulation was monitored by the activated clotting time and heparin concentration. Perioperative hemostasis was evaluated by thromboelastometry, platelet aggregation, and several plasma coagulation markers. RESULTS: Eighteen patients were included in this study. During cooling, tube-based activated clotting time increased from 719 (95% confidence interval = 566-872 seconds) to 1,273 (95% confidence interval = 1,136-1,410 seconds; p < 0.01) and the cartridge-based activated clotting time increased from 693 (95% confidence interval = 590-796 seconds) to 883 (95% confidence interval = 806-960 seconds; p < 0.01), while thrombin-antithrombin showed an eightfold increase. The heparin concentration showed a slightly declining trend during cardiopulmonary bypass. After protamine administration (protamine-to-heparin bolus ratio of 0.82 (0.71-0.90)), more than half of the patients showed an intrinsically activated coagulation test and intrinsically activated coagulation test without heparin effect clotting time >240 seconds. Platelet aggregation through activation of the P2Y12 (adenosine diphosphate test) and thrombin receptor (thrombin receptor activating peptide-6 test) decreased (both -33%) and PF4 levels almost doubled (from 48 (95% confidence interval = 42-53 ng/mL) to 77 (95% confidence interval = 71-82 ng/mL); p < 0.01) between weaning from cardiopulmonary bypass and 3 minutes after protamine administration. CONCLUSION: This study shows a wide variation in individual heparin sensitivity in patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest. Although activated clotting time-guided anticoagulation management may underestimate the level of anticoagulation and consequently result in a less profound inhibition of hemostatic activation, this study lacked power to detect adverse outcomes.
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Ponte Cardiopulmonar , Parada Circulatória Induzida por Hipotermia Profunda , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Coagulação Sanguínea , Ponte Cardiopulmonar/efeitos adversos , Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Endarterectomia , Heparina/farmacologia , Heparina/uso terapêutico , HumanosRESUMO
AIM: Haemodynamic normalisation is the ultimate goal of pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). However, whether normalisation of haemodynamics translates into normalisation of exercise capacity is unknown. The incidence, determinants and clinical implications of exercise intolerance after PEA are unknown. We performed a prospective analysis to determine the incidence of exercise intolerance after PEA, assess the relationship between exercise capacity and (resting) haemodynamics and search for preoperative predictors of exercise intolerance after PEA. METHODS: According to clinical protocol all patients underwent cardiopulmonary exercise testing (CPET), right heart catheterisation and cardiac magnetic resonance (CMR) imaging before and 6â months after PEA. Exercise intolerance was defined as a peak oxygen consumption (V'O2 ) <80% predicted. CPET parameters were judged to determine the cause of exercise limitation. Relationships were analysed between exercise intolerance and resting haemodynamics and CMR-derived right ventricular function. Potential preoperative predictors of exercise intolerance were analysed using logistic regression analysis. RESULTS: 68 patients were included in the final analysis. 45 (66%) patients had exercise intolerance 6â months after PEA; in 20 patients this was primarily caused by a cardiovascular limitation. The incidence of residual pulmonary hypertension was significantly higher in patients with persistent exercise intolerance (p=0.001). However, 27 out of 45 patients with persistent exercise intolerance had no residual pulmonary hypertension. In the multivariate analysis, preoperative transfer factor of the lung for carbon monoxide (T LCO) was the only predictor of exercise intolerance after PEA. CONCLUSIONS: The majority of CTEPH patients have exercise intolerance after PEA, often despite normalisation of resting haemodynamics. Not all exercise intolerance after PEA is explained by the presence of residual pulmonary hypertension, and lower preoperative T LCO was a strong predictor of exercise intolerance 6â months after PEA.
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Endarterectomia , Hipertensão Pulmonar , Embolia Pulmonar , Doença Crônica , Tolerância ao Exercício , Humanos , Hipertensão Pulmonar/cirurgia , Pulmão , Estudos Prospectivos , Artéria Pulmonar/cirurgia , Embolia Pulmonar/complicações , Resultado do TratamentoRESUMO
OBJECTIVE: Little is known about the prevalence and degree of deformation of surgically implanted aortic biological valve prostheses (bio-sAVRs). We assessed bio-sAVR deformation using multidetector-row computed tomography (MDCT). METHODS: Three imaging databases were searched for patients with MDCT performed after bio-sAVR implantation. Minimal and maximal valve ring diameters were obtained in systole and/or diastole, depending on the acquired cardiac phase(s). The eccentricity index (EI) was calculated as a measure of deformation as (1 - (minimal diameter/maximal diameter)) × 100%. EI of < 5% was considered none or trivial deformation, 5-10% mild deformation, and > 10% non-circular. Indications for MDCT and implanted valve type were retrieved. RESULTS: One hundred fifty-two scans of bio-sAVRs were included. One hundred seventeen measurements were performed in systole and 35 in diastole. None or trivial deformation (EI < 5%) was seen in 67/152 (44%) of patients. Mild deformation (EI 5-10%) was seen in 59/152 (39%) and non-circularity was found in 26/152 (17%) of cases. Overall, median EI was 5.5% (IQR 3.4-7.8). In 77 patients, both systolic and diastolic measurements were performed from the same scan. For these scans, the median EI was 6.5% (IQR 3.4-10.2) in systole and 5.1% (IQR3.1-7.6) in diastole, with a significant difference between both groups (p = 0.006). CONCLUSIONS: Surgically implanted aortic biological valve prostheses show mild deformation in 39% of cases and were considered non-circular in 17% of studied valves. KEY POINTS: ⢠Deformation of surgically implanted aortic valve bioprostheses (bio-sAVRs) can be adequately assessed using MDCT. ⢠Bio-sAVRs show at least mild deformation (eccentricity index > 5%) in 56% of studied cases and were considered non-circular (eccentricity index > 10%) in 17% of studied valves. ⢠The higher deformity rate found in bio-sAVRs with (suspected) valve pathology could suggest that geometric deformity may play a role in leaflet malformation and thrombus formation similar to that of transcatheter heart valves.
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Valva Aórtica/diagnóstico por imagem , Bioprótese , Próteses Valvulares Cardíacas , Valva Aórtica/cirurgia , Diástole , Implante de Prótese de Valva Cardíaca , Humanos , Tomografia Computadorizada Multidetectores , Falha de Prótese , Sístole , Resultado do TratamentoRESUMO
Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients (N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls (N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast-twitch muscle fibers of CTEPH patients, resulting in a â¼40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 µM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients.
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Diafragma/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Idoso , Sinalização do Cálcio , Diafragma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Lenta/fisiologia , Debilidade Muscular , Embolia Pulmonar/fisiopatologiaRESUMO
OBJECTIVES: Recent studies have proposed additional multidetector-row CT (MDCT) for prosthetic heart valve (PHV) dysfunction. References to discriminate physiological from pathological conditions early after implantation are lacking. We present baseline MDCT findings of PHVs 6 weeks post implantation. METHODS: Patients were prospectively enrolled and TTE was performed according to clinical guidelines. 256-MDCT images were systematically assessed for leaflet excursions, image quality, valve-related artefacts, and pathological and additional findings. RESULTS: Forty-six patients were included comprising 33 mechanical and 16 biological PHVs. Overall, MDCT image quality was good and relevant regions remained reliably assessable despite mild-moderate PHV-artefacts. MDCT detected three unexpected valve-related pathology cases: (1) prominent subprosthetic tissue, (2) pseudoaneurysm and (3) extensive pseudoaneurysms and valve dehiscence. The latter patient required valve surgery to be redone. TTE only showed trace periprosthetic regurgitation, and no abnormalities in the other cases. Additional findings were: tilted aortic PHV position (n = 3), pericardial haematoma (n = 3) and pericardial effusion (n = 3). Periaortic induration was present in 33/40 (83 %) aortic valve patients. CONCLUSIONS: MDCT allowed evaluation of relevant PHV regions in all valves, revealed baseline postsurgical findings and, despite normal TTE findings, detected three cases of unexpected, clinically relevant pathology. KEY POINTS: ⢠Postoperative MDCT presents baseline morphology relevant for prosthetic valve follow-up. ⢠83 % of patients show periaortic induration 6 weeks after aortic valve replacement. ⢠MDCT detected three cases of clinically relevant pathology not found with TTE. ⢠Valve dehiscence detection by MDCT required redo valve surgery in one patient. ⢠MDCT is a suitable and complementary imaging tool for follow-up purposes.
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Insuficiência da Valva Aórtica/cirurgia , Falha de Prótese/efeitos adversos , Adulto , Idoso , Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Feminino , Seguimentos , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Cuidados Pós-Operatórios/métodos , Estudos Prospectivos , Recidiva , Padrões de ReferênciaRESUMO
OBJECTIVES: Retrospective ECG-gated multidetector-row computed tomography (MDCT) is increasingly used for the assessment of prosthetic heart valve (PHV) dysfunction, but is also hampered by PHV-related artefacts/cardiac arrhythmias. Furthermore, it is performed without nitroglycerine or heart rate correction. The purpose was to determine whether MDCT performed before potential redo-PHV surgery is feasible for concomitant coronary artery stenosis assessment and can replace invasive coronary angiography (CAG). METHODS: PHV patients with CAG and MDCT were identified. Based on medical history, two groups were created: (I) patients with no known coronary artery disease (CAD), (II) patients with known CAD. All images were scored for the presence of significant (>50 %) stenosis. CAG was the reference test. RESULTS: Fifty-one patients were included. In group I (n = 38), MDCT accurately ruled out significant stenosis in 19/38 (50 %) patients, but could not replace CAG in the remaining 19/38 (50 %) patients due to non-diagnostic image quality (n = 16) or significant stenosis (n = 3) detection. In group II (n = 13), MDCT correctly found no patients without significant stenosis, requiring CAG imaging in all. MDCT assessed patency in 16/19 (84 %) grafts and detected a hostile anatomy in two. CONCLUSION: MDCT performed for PHV dysfunction assessment can replace CAG (100 % accurate) in approximately half of patients without previously known CAD. KEY POINTS: ⢠Retrospective MDCT is increasingly used for prosthetic heart valve dysfunction assessment ⢠In case of PHV reoperation, invasive coronary angiography is also required ⢠MDCT can replace CAG in 50 % of patients without coronary artery disease ⢠When conclusive for coronary assessment, MDCT stenosis rule out is highly accurate ⢠Replacing CAG saves associated risks of distant embolization of thrombi or vegetations.
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Angiografia Coronária/métodos , Análise de Falha de Equipamento/métodos , Próteses Valvulares Cardíacas , Valvas Cardíacas/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Cuidados Pré-Operatórios/métodos , Idoso , Estenose Coronária/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Prótese , Reoperação , Reprodutibilidade dos TestesAssuntos
Hipertensão Pulmonar/etiologia , Embolia Pulmonar/complicações , Disfunção Ventricular Direita/fisiopatologia , Idoso , Doença Crônica , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/fisiopatologia , Estudos Retrospectivos , Disfunção Ventricular Direita/diagnóstico por imagemRESUMO
PURPOSE: The purpose of this study was to compare multidetector-row computed tomography (MDCT) leaflet restriction measurements with fluoroscopy measurements in commonly used mechanical prosthetic heart valves (PHVs). METHODS: Four mechanical PHVs (ON-X, Carbomedics, St. Jude, and Medtronic Hall) were imaged in a pulsatile model using fluoroscopy and 64-detector-row computed tomography. Five image acquisitions of each PHV without (1) and with (4) restricted leaflet closure were made. Three observers measured closure angles on fluoroscopy and MDCT. Data were analyzed using intraclass correlation coefficient (ICC) and Bland-Altman plots. RESULTS: Interobserver agreement was high in restricted and non-restricted leaflets on both modalities (ICCs >0.995). MDCT and fluoroscopy showed high agreements (ICCs >0.989). Median MDCT closure angle measurements differed at most -2 to +2 degrees from fluoroscopy in the restricted and -1 to +2 degrees in the non-restricted leaflets. CONCLUSIONS: MDCT allows measurement of leaflet motion with a maximal median discrepancy of 2 degrees. Both MDCT and fluoroscopy detect restricted leaflet closure with great accuracy.
Assuntos
Fluoroscopia/métodos , Próteses Valvulares Cardíacas , Valvas Cardíacas/diagnóstico por imagem , Valvas Cardíacas/cirurgia , Tomografia Computadorizada Multidetectores/métodos , Imagens de Fantasmas , Análise de Falha de Equipamento/métodos , Fluoroscopia/instrumentação , Humanos , Tomografia Computadorizada Multidetectores/instrumentação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The correlation between hemodynamics and degree of pulmonary vascular obstruction (PVO) is known to be poor in chronic thromboembolic pulmonary hypertension (CTEPH), which makes the selection of patients eligible for pulmonary endarterectomy (PEA) challenging. It can be postulated that patients with similar PVO but different hemodynamic severity have different postoperative hemodynamics and exercise capacity. Therefore, we aimed to assess the effects of PEA on hemodynamics and exercise physiology in mild and severe CTEPH patients. We retrospectively studied 18 CTEPH patients with a mild hemodynamic profile (mean pulmonary arterial pressure [mPAP] between 25 and 30 mmHg at rest) and CTEPH patients with a more severe hemodynamic profile (mPAP > 30 mmHg), matched by age, gender, and PVO. Cardiopulmonary exercise testing parameters were evaluated at baseline and 18 months following PEA. At baseline, exercise capacity, defined as oxygen uptake, was less severely impaired in the mild CTEPH group compared to the severe CTEPH group. After PEA, in the mild CTEPH group, ventilatory efficiency and oxygen pulse improved significantly (p < 0.05), however, the change in ventilatory efficiency and oxygen pulse was smaller compared to the severe CTEPH group. Only in the severe CTEPH group exercise capacity improved significantly (p < 0.001). Hence, in the present study, postoperative hemodynamic outcome and the CPET-determined recovery of exercise capacity in mild CTEPH patients did not differ from a matched group of severe CTEPH patients.
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BACKGROUND: Long-term changes in exercise capacity and cardiopulmonary hemodynamics after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been poorly described. METHODS: We analyzed the data from 2 prospective surgical CTEPH cohorts in Hammersmith Hospital, London, and Amsterdam UMC. A structured multimodal follow-up was adopted, consisting of right heart catheterization, cardiac magnetic resonance imaging, and cardiopulmonary exercise testing before and after PEA. Preoperative predictors of residual pulmonary hypertension (PH; mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance ≥2 WU) and long-term exercise intolerance (VO2max <80%) at 18 months were analyzed. RESULTS: A total of 118 patients (61 from London and 57 from Amsterdam) were included in the analysis. Both cohorts displayed a significant improvement of pulmonary hemodynamics, right ventricular (RV) function, and exercise capacity 6 months after PEA. Between 6 and 18 months after PEA, there were no further improvements in hemodynamics and RV function, but the proportion of patients with impaired exercise capacity was high and slightly increased over time (52%-59% from 6 to 18 months). Long-term exercise intolerance was common and associated with preoperative diffusion capacity for carbon monoxide (DLCO), preoperative mixed venous oxygen saturation, and postoperative PH and right ventricular ejection fraction (RVEF). Clinically significant RV deterioration (RVEF decline >3%; 5 [9%] of 57 patients) and recurrent PH (5 [14%] of 36 patients) rarely occurred beyond 6 months after PEA. Age and preoperative DLCO were predictors of residual PH post-PEA. CONCLUSIONS: Restoration in exercise tolerance, cardiopulmonary hemodynamics, and RV function occurs within 6 months. No substantial changes occurred between 6 and 18 months after PEA in the Amsterdam cohort. Nevertheless, long-term exercise intolerance is common and associated with postoperative RV function.
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Hipertensão Pulmonar , Embolia Pulmonar , Humanos , Tolerância ao Exercício , Embolia Pulmonar/complicações , Embolia Pulmonar/cirurgia , Volume Sistólico , Estudos Prospectivos , Função Ventricular Direita , Hemodinâmica , Endarterectomia/métodos , Artéria Pulmonar/cirurgia , Doença CrônicaRESUMO
Background Pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension improves resting hemodynamics and right ventricular (RV) function. Because exercise tolerance frequently remains impaired, RV function may not have completely normalized after PEA. Therefore, we performed a detailed invasive hemodynamic study to investigate the effect of PEA on RV function during exercise. Methods and Results In this prospective study, all consenting patients with chronic thromboembolic pulmonary hypertension eligible for surgery and able to perform cycle ergometry underwent cardiac magnetic resonance imaging, a maximal cardiopulmonary exercise test, and a submaximal invasive cardiopulmonary exercise test before and 6 months after PEA. Hemodynamic assessment and analysis of RV pressure curves using the single-beat method was used to determine load-independent RV contractility (end systolic elastance), RV afterload (arterial elastance), RV-arterial coupling (end systolic elastance-arterial elastance), and stroke volume both at rest and during exercise. RV rest-to-exercise responses were compared before and after PEA using 2-way repeated-measures analysis of variance with Bonferroni post hoc correction. A total of 19 patients with chronic thromboembolic pulmonary hypertension completed the entire study protocol. Resting hemodynamics improved significantly after PEA. The RV exertional stroke volume response improved 6 months after PEA (79±32 at rest versus 102±28 mL during exercise; P<0.01). Although RV afterload (arterial elastance) increased during exercise, RV contractility (end systolic elastance) did not change during exercise either before (0.43 [0.32-0.58] mm Hg/mL versus 0.45 [0.22-0.65] mm Hg/mL; P=0.6) or after PEA (0.32 [0.23-0.40] mm Hg/mL versus 0.28 [0.19-0.44] mm Hg/mL; P=0.7). In addition, mean pulmonary artery pressure-cardiac output and end systolic elastance-arterial elastance slopes remained unchanged after PEA. Conclusions The exertional RV stroke volume response improves significantly after PEA for chronic thromboembolic pulmonary hypertension despite a persistently abnormal afterload and absence of an RV contractile reserve. This may suggest that at mildly elevated pulmonary pressures, stroke volume is less dependent on RV contractility and afterload and is primarily determined by venous return and conduit function.
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Hipertensão Pulmonar , Disfunção Ventricular Direita , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/cirurgia , Função Ventricular Direita , Estudos Prospectivos , Doença Crônica , Endarterectomia/efeitos adversos , Artéria Pulmonar/cirurgiaAssuntos
Endarterectomia , Hipertensão Pulmonar/cirurgia , Artéria Pulmonar , Calcificação Vascular/cirurgia , Adulto , Angiografia por Tomografia Computadorizada , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Calcificação Vascular/complicações , Calcificação Vascular/diagnóstico por imagemRESUMO
OBJECTIVES: Multidetector computed tomography (MDCT) has diagnostic value for the evaluation of prosthetic heart valve (PHV) dysfunction but it is hampered by artefacts. We hypothesised that image acquisition using prospective triggering instead of retrospective gating would reduce artefacts related to pulsating PHV. METHODS: In a pulsatile in vitro model, a mono- and bileaflet PHV were imaged using 256 MDCT at 60, 75 and 90 beats per minute (BPM) with either retrospective gating (120 kV, 600 mAs, pitch 0.2, CTDI(vol) 39.8 mGy) or prospective triggering (120 kV, 200 mAs, CTDI(vol) 13.3 mGy). Two thresholds (>175 and <-45HU), derived from the density of surrounding structures, were used for quantification of hyper- and hypodense artefacts. Image noise and artefacts were compared between protocols. RESULTS: Prospective triggering reduced hyperdense artefacts for both valves at every BPM (P = 0.001 all comparisons). Hypodense artefacts were reduced for the monoleaflet valve at 60 (P = 0.009), 75 (P = 0.016) and 90 BPM (P = 0.001), and for the bileaflet valves at 60 (P = 0.001), 90 (P = 0.001) but not at 75 BPM (P = 0.6). Prospective triggering reduced image noise at 60 (P = 0.001) and 75 (P < 0.03) but not at 90 BPM. CONCLUSIONS: Compared with retrospective gating, prospective triggering reduced most artefacts related to pulsating PHV in vitro. KEY POINTS: ⢠Computed tomographic images are often degraded by prosthetic heart valve-induced artefacts ⢠Prospective triggering reduces prosthetic heart valve-induced artefacts in vitro ⢠Artefact reduction at 90 beats per minute occurs without image noise reduction ⢠Prospective triggering may improve CT image quality of moving hyperdense structures.
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Artefatos , Técnicas de Imagem de Sincronização Cardíaca/métodos , Eletrocardiografia/métodos , Próteses Valvulares Cardíacas , Valvas Cardíacas/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Valvas Cardíacas/cirurgia , Humanos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/instrumentaçãoRESUMO
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by elevated pulmonary arterial pressure and organized thrombi within pulmonary arteries. Riociguat is a soluble guanylate cyclase stimulator and is approved for patients with inoperable CTEPH or residual pulmonary hypertension after pulmonary endarterectomy (PEA). Previous work suggested that riociguat treatment is associated with an increased risk of bleeding, although the mechanism is unclear. The aim of this study is to assess how riociguat affects primary hemostasis by studying its effect on the interaction between platelets and endothelial cells derived from CTEPH patients. Pulmonary artery endothelial cells (PAECs) were isolated from thrombus-free regions of PEA material. Purified PAECs were cultured in flow chambers and were stimulated with 0.1 and 1 µM riociguat for 24 h before flow experiments. After stimulation with histamine, PAECs were exposed to platelets under shear stress. Platelet adhesion and expression of von Willebrand Factor (VWF) were evaluated to assess the role of riociguat in hemostasis. Under dynamic conditions, 0.1 and 1.0 µM of riociguat suppressed platelet adhesion on the surface of PAECs. Although riociguat did not affect intracellular expression and secretion of VWF, PAECs stimulated with riociguat produced fewer VWF strings than unstimulated PAECs. Flow cytometry suggested that decreased VWF string formation upon riociguat treatment may be associated with suppressed cell surface expression of P-selectin, a protein that stabilizes VWF anchoring on the endothelial surface. In conclusion, Riociguat inhibits VWF string elongation and platelet adhesion on the surface of CTEPH-PAECs, possibly by reduced P-selectin cell surface expression.
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Chronic thromboembolic pulmonary hypertension (CTEPH) has a poor prognosis if left untreated but can be cured by pulmonary endarterectomy (PEA). Massive endobronchial pulmonary hemorrhage is a potentially fatal complication of PEA, occurring in 0.5%of patients. We describe the use of an endobronchial blocker (EBB) as an additional method to successfully treat massive, focal pulmonary hemorrhage during PEA.
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Oxigenação por Membrana Extracorpórea , Hipertensão Pulmonar , Embolia Pulmonar , Doença Crônica , Endarterectomia/métodos , Oxigenação por Membrana Extracorpórea/métodos , Hemorragia/etiologia , Hemorragia/cirurgia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/cirurgia , Recém-Nascido , Artéria Pulmonar/cirurgia , Embolia Pulmonar/complicações , Embolia Pulmonar/cirurgia , Resultado do TratamentoRESUMO
Background: The success of pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is usually evaluated by performing a right heart catheterisation (RHC). Here, we investigate whether residual pulmonary hypertension (PH) can be sufficiently excluded without the need for a RHC, by making use of early post-operative haemodynamics, or N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiopulmonary exercise testing (CPET) and transthoracic echocardiography (TTE) 6â months after PEA. Methods: In an observational analysis, residual PH after PEA measured by RHC was related to haemodynamic data from the post-operative intensive care unit time and data from a 6-month follow-up assessment including NT-proBNP, TTE and CPET. After dichotomisation and univariate analysis, sensitivity, specificity, positive predictive value, negative predictive value (NPV) and likelihood ratios were calculated. Results: Thirty-six out of 92 included patients had residual PH 6â months after PEA (39%). Correlation between early post-operative and 6-month follow-up mean pulmonary artery pressure was moderate (Spearman rho 0.465, p<0.001). Early haemodynamics did not predict late success. NT-proBNP >300â ng·L-1 had insufficient NPV (0.71) to exclude residual PH. Probability for PH on TTE had a moderate NPV (0.74) for residual PH. Peak oxygen consumption (V'O2 ) <80% predicted had the highest sensitivity (0.85) and NPV (0.84) for residual PH. Conclusions: CPET 6â months after PEA, and to a lesser extent TTE, can be used to exclude residual CTEPH, thereby safely reducing the number of patients needing to undergo re-RHC after PEA.
RESUMO
OBJECTIVES: Multidetector computed tomography (MDCT) can detect the cause of prosthetic heart valve (PHV) dysfunction but is hampered by valve-induced artifacts. We quantified artifacts of four PHV using a pulsatile in-vitro model and assessed the relation to leaflet motion and valve design. METHODS: A Medtronic Hall tilting disc (MH), and Carbomedics (CM), St Jude (SJM), and ON-X bileaflet valves underwent CT in an in-vitro model using retrospective gating with a 64 detector CT system in stationary and pulsatile conditions. Artifacts and radiopaque component volumes were quantified with thresholds based on surrounding structures and valvular components. RESULTS: Hypodense artifacts volumes (mm³) were 1,029 ± 147, 535 ± 53, 371 ± 16, and 366 ± 18 for the SJM, MH, CM and ON-X valves (p < 0.001 except for the latter two valves p = 0.43). Hyperdense artifact volumes were 3,546 ± 141, 2,387 ± 103, 2,003 ± 102, and 3,033 ± 31 for the SJM, MH, CM and ON-X valve, respectively (all differences p < 0.001). Leaflet motion affected hypodense (F = 41.5, p < 0.001) and hyperdense artifacts (F = 53.7, p < 0.001). Closed and moving leaflets were associated with the least and the most artifacts respectively (p < 0.001, both artifact types). CONCLUSION: Both valve design and leaflet motion affect PHV-induced artifacts. Best imaging results may be expected for the CM valve during phases in which the leaflets are closed.
Assuntos
Cardiologia/métodos , Próteses Valvulares Cardíacas , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada Multidetectores/métodos , Algoritmos , Artefatos , Eletrocardiografia/métodos , Humanos , Modelos Estatísticos , Modelos Teóricos , Movimento (Física) , Desenho de Prótese , Fluxo PulsátilRESUMO
OBJECTIVES: Multidetector CT (MDCT) has shown potential for prosthetic heart valve (PHV) assessment. We assessed the image quality of different PHV types to determine which valves are suitable for MDCT evaluation. METHODS: All ECG-gated CTs performed in our institutions since 2003 were reviewed for the presence of PHVs. After reconstruction in 3 specific PHV planes, image quality of the supravalvular, perivalvular, subvalvular and valvular regions was scored on a four-point scale (1 = non-diagnostic, 2 = moderate, 3 = good and 4 = excellent) by two independent observers. RESULTS: Eighty-four CT examinations (66 cardiac, 18 limited-dose aortic protocols) of 83 patients with a total of 91 PHVs in the aortic (n = 71), mitral (n = 17), pulmonary (n = 1) and tricuspid (n = 2) position were included. CT was performed on a 16-slice (n = 4), 64-slice (n = 28) or 256-slice (n = 52) MDCT system. Median image quality scores for the supra-, peri- and subvalvular regions and valvular detail were (3.5, 3.3, 3.5 and 3.5, respectively) for bileaflet PHV; (3.0, 3.0, 3.5 and 3.0, respectively) for Medtronic Hall PHV; (1.0, 1.0, 1.0 and 1.0, respectively) for Björk-Shiley and Sorin monoleaflet PHV and (3.5, 3.5, 4.0 and 2.0 respectively) for biological PHV. CONCLUSION: Currently implanted PHVs have good image quality on MDCT and are suitable for MDCT evaluation.