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1.
PLoS One ; 15(9): e0235824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881898

RESUMO

Pulmonary hypertension due to left heart disease (PH-LHD) is a momentous pulmonary hypertension disease, and left heart disease is the most familiar cause. Mechanical stretching may be a crucial cause of vascular remodeling. While, the underlining mechanism of mechanical stretching-induced in remodeling of pulmonary vein in the early stage of PH-LHD has not been completely elucidated. In our study, the PH-LHD model rats were successfully constructed. After 25 days, doppler echocardiography and hemodynamic examination were performed. In addition, after treatment, the levels of matrix metalloproteinase-9 (MMP-9) and transforming growth factor-ß1 (TGF-ß1) were determined by ELISA, immunohistochemistry and western blot assays in the pulmonary veins. Moreover, the pathological change of pulmonary tissues was evaluated by H&E staining. Our results uncovered that left ventricular insufficiency and interventricular septal shift could be observed in PH-LHD model rats, and the right ventricular systolic pressure (RVSP) and mean left atrial pressure (mLAP) were also elevated in PH-LHD model rats. Meanwhile, we found that MMP-9 and TGF-ß1 could be highly expressed in PH-LHD model rats. Besides, we revealed that stretch-activated channel (SAC)/mitogen-activated protein kinases (MAPKs) signaling pathway could be involved in the upregulations of MMP-9 and TGF-ß1 mediated by mechanical stretching in pulmonary vein. Therefore, current research revealed that mechanical stretching induced the increasing expressions of MMP-9 and TGF-ß1 in pulmonary vein, which could be mediated by activation of SAC/MAPKs signaling pathway in the early stage of PH-LHD.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Sistema de Sinalização das MAP Quinases , Metaloproteinase 9 da Matriz/metabolismo , Veias Pulmonares/fisiopatologia , Fator de Crescimento Transformador beta1/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Animais , Fenômenos Biomecânicos , Modelos Animais de Doenças , Ativação Enzimática , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Masculino , Veias Pulmonares/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , Remodelação Vascular , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/metabolismo
3.
Ann Am Thorac Soc ; 17(8): 918-921, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32735170

RESUMO

Amid efforts to care for the large number of patients with coronavirus disease (COVID-19), there has been considerable speculation about whether the lung injury seen in these patients is different than acute respiratory distress syndrome from other causes. One idea that has garnered considerable attention, particularly on social media and in free open-access medicine, is the notion that lung injury due to COVID-19 is more similar to high-altitude pulmonary edema (HAPE). Drawing on this concept, it has also been proposed that treatments typically employed in the management of HAPE and other forms of acute altitude illness-pulmonary vasodilators and acetazolamide-should be considered for COVID-19. Despite some similarities in clinical features between the two entities, such as hypoxemia, radiographic opacities, and altered lung compliance, the pathophysiological mechanisms of HAPE and lung injury due to COVID-19 are fundamentally different, and the entities cannot be viewed as equivalent. Although of high utility in the management of HAPE and acute mountain sickness, systemically delivered pulmonary vasodilators and acetazolamide should not be used in the treatment of COVID-19, as they carry the risk of multiple adverse consequences, including worsened ventilation-perfusion matching, impaired carbon dioxide transport, systemic hypotension, and increased work of breathing.


Assuntos
Doença da Altitude , Infecções por Coronavirus , Hipertensão Pulmonar , Pandemias , Pneumonia Viral , Síndrome do Desconforto Respiratório do Adulto , Acetazolamida/farmacologia , Doença da Altitude/fisiopatologia , Doença da Altitude/terapia , Betacoronavirus/isolamento & purificação , Inibidores da Anidrase Carbônica/farmacologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Lesão Pulmonar/etiologia , Lesão Pulmonar/fisiopatologia , Lesão Pulmonar/terapia , Nifedipino/farmacologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Vasodilatadores/farmacologia
4.
Lancet Respir Med ; 8(9): 873-884, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32730752

RESUMO

BACKGROUND: In pulmonary hypertension subgroups, elevated pulmonary vascular resistance (PVR) of 3·0 Wood units or more is associated with poor prognosis. However, the spectrum of PVR risk in pulmonary hypertension is not known. To address this area of uncertainty, we aimed to analyse the relationship between PVR and adverse clinical outcomes in pulmonary hypertension. METHODS: We did a retrospective cohort study of all patients undergoing right heart catheterisation (RHC) in the US Veterans Affairs health-care system (Oct 1, 2007-Sep 30, 2016). Patients were included in the analyses if data from a complete RHC and at least 1 year of follow-up were available. Both inpatients and outpatients were included, but individuals with missing mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure, or cardiac output were excluded. The primary outcome measure was time to all-cause mortality assessed by the Veteran Affairs vital status file. Cox proportional hazards models were used to assess the association between PVR and outcomes, and the mortality hazard ratio was validated in a RHC cohort from Vanderbilt University Medical Center (Sept 24, 1998-June 1, 2016). FINDINGS: The primary cohort (N=40 082; 38 751 [96·7%] male; median age 66·5 years [IQR 61·1-73·5]; median follow-up 1153 days [IQR 570-1971]), included patients with a history of heart failure (23 201 [57·9%]) and chronic obstructive pulmonary disease (13 348 [33·3%]). We focused on patients at risk for pulmonary hypertension based on a mPAP of at least 19 mm Hg (32 725 [81·6%] of 40 082). When modelled as a continuous variable, the all-cause mortality hazard for PVR was increased at around 2·2 Wood units compared with PVR of 1·0 Wood unit. Among patients with a mPAP of at least 19 mm Hg and pulmonary artery wedge pressure of 15 mm Hg or less, the adjusted hazard ratio (HR) for mortality was 1·71 (95% CI 1·59-1·84; p<0·0001) and for heart failure hospitalisation was 1·27 (1·13-1·43; p=0·0001), when comparing PVR of 2·2 Wood units or more to less than 2·2 Wood units. The validation cohort (N=3699, 1860 [50·3%] male, median age 60·4 years [49·5-69·2]; median follow-up 1752 days [IQR 1281-2999]) included 2870 patients [77·6%] with mPAP of at least 19 mm Hg (1418 [49·4%] male). The adjusted mortality HR for patients in the mPAP of 19 mm Hg or more group and with PVR of 2·2 Wood units or more and pulmonary artery wedge pressure of 15 mm or less Hg (1221 [42·5%] of 2870) was 1·81 (95% CI 1·33-2·47; p=0·0002). INTERPRETATION: These data widen the continuum of clinical risk for mortality and heart failure in patients referred for RHC with elevated pulmonary artery pressure to include PVR of around 2.2 Wood units and higher. Testing the generalisability of these findings in at-risk populations with fewer cardiopulmonary comorbidities is warranted. FUNDING: None.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Resistência Vascular , Idoso , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/terapia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resistência Vascular/fisiologia
5.
J Cardiovasc Magn Reson ; 22(1): 50, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32698897

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) associated with pulmonary hypertension (PH) is a significant source of morbidity and mortality in premature infants. Recent advances have allowed the use of cardiovascular magnetic resonance (CMR) in the assessment of respiratory and cardiac disease in infants with BPD. In adults and older pediatric patients, decreased CMR interventricular septal curvature correlates with increased mean pulmonary artery pressure and pulmonary vascular resistance. The current study sought to determine the relationship of CMR derived septal curvature in neonates with BPD and BPD-PH with a need for PH therapy. METHODS: Forty moderate or severe BPD and 12 mild BPD or control infants were imaged without contrast between 38 and 47 weeks post-menstrual age on a neonatal-sized, neonatal intensive care unit-sited 1.5 T CMR scanner. CMR indices including eccentricity index (CMR-EI) and septal curvature were measured and compared to BPD severity and clinical outcomes including hospital length of stay (LOS), duration of respiratory support, respiratory support level at discharge and PH therapy. RESULTS: CMR-EI was directly associated and septal curvature was inversely associated with BPD severity. In a univariate analysis, CMR-EI and septal curvature were associated with increased hospital LOS, duration of respiratory support, respiratory support at hospital discharge, and need for PH therapy. In multivariable analysis CMR-EI was associated with hospital LOS and duration of respiratory support and septal curvature was associated with respiratory support at hospital discharge. Septal curvature was the only clinical or CMR variable associated with need for PH therapy (R2 = 0.66, p = 0.0014) in multivariable analysis demonstrating improved discrimination beyond CMR-EI. CONCLUSIONS: CMR derived septal curvature correlates significantly with clinical outcomes including hospital LOS, duration of respiratory support, respiratory support level at hospital discharge, and PH therapy in neonates with BPD and BPD-PH. Further, CMR derived septal curvature demonstrated improved discrimination of need for PH therapy and respiratory support at discharge compared to clinical variables and other CMR indices, supporting septal curvature as a non-invasive marker of PH in this population with potential to guide management strategies.


Assuntos
Pressão Arterial , Displasia Broncopulmonar/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Artéria Pulmonar/fisiopatologia , Resistência Vascular , Septo Interventricular/diagnóstico por imagem , Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/terapia , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Recém-Nascido , Tempo de Internação , Masculino , Valor Preditivo dos Testes , Artéria Pulmonar/efeitos dos fármacos , Terapia Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacos , Septo Interventricular/efeitos dos fármacos , Septo Interventricular/fisiopatologia
6.
Cardiol Young ; 30(9): 1358-1359, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32624054

RESUMO

A 16-year-old girl with history of treated congenital mitral valve disease and signs of respiratory infection was admitted to our paediatric cardiology department. She was tested positive for severe acute respiratory syndrome coronavirus 2. Despite her severe pre-existing cardiac conditions with pulmonary hypertension, atrial arrhythmias and mitral valve stenosis, the infection did not lead to any cardiac or pulmonary deterioration. In adults, cardiac co-morbidities are known risk factors for a severe course of coronavirus disease 2019 infections. This case illustrates that in children even severe cardiac disease is not necessarily associated with a severe course of coronavirus disease 2019.


Assuntos
Infecções por Coronavirus , Átrios do Coração , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Estenose da Valva Mitral , Pandemias , Pneumonia Viral , Falha de Prótese/efeitos adversos , Adolescente , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Ecocardiografia/métodos , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Valva Mitral/patologia , Valva Mitral/fisiopatologia , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/congênito , Insuficiência da Valva Mitral/cirurgia , Estenose da Valva Mitral/complicações , Estenose da Valva Mitral/congênito , Estenose da Valva Mitral/cirurgia , Tamanho do Órgão , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Resultado do Tratamento
7.
J Comput Assist Tomogr ; 44(4): 578-585, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649425

RESUMO

OBJECTIVE: The objective of this study was to assess the correlation between dual-energy computed tomography quantitative parameters and hemodynamics in patients with chronic thromboembolic pulmonary hypertension. METHODS: Dual-energy computed tomography of 52 chronic thromboembolic pulmonary hypertension patients were evaluated retrospectively. The mean lung perfused blood volume (lung PBV) and the mean pulmonary artery (PA) enhancement measured at pulmonary parenchymal phase were compared with the hemodynamics by Spearman rank correlation coefficient (rs) and receiver operating characteristic analysis. RESULTS: Lung PBV was correlated with mean pulmonary arterial pressure (rs = 0.47, P < 0.001). Pulmonary artery enhancement was correlated with cardiac index (rs = -0.49, P < 0.001) and pulmonary vascular resistance (rs = 0.48, P < 0.001). The areas under the curves were 0.86 for lung PBV to predict mean pulmonary arterial pressure of >50 mm Hg and 0.86 for PA enhancement to predict pulmonary vascular resistance of >1000 dyne·s/cm. CONCLUSIONS: Lung PBV and PA enhancement could be indicators of hemodynamics.


Assuntos
Hipertensão Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Volume Sanguíneo , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/fisiopatologia , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
9.
J Vis Exp ; (160)2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32568218

RESUMO

Pulmonary Hypertension (PH) is a pathophysiological condition, defined by a mean pulmonary arterial pressure exceeding 25 mm Hg at rest, as assessed by right heart catheterization. A broad spectrum of diseases can lead to PH, differing in their etiology, histopathology, clinical presentation, prognosis, and response to treatment. Despite significant progress in the last years, PH remains an uncured disease. Understanding the underlying mechanisms can pave the way for the development of new therapies. Animal models are important research tools to achieve this goal. Currently, there are several models available for recapitulating PH. This protocol describes a two-hit mouse PH model. The stimuli for PH development are hypoxia and the injection of SU5416, a vascular endothelial growth factor (VEGF) receptor antagonist. Three weeks after initiation of Hypoxia/SU5416, animals develop pulmonary vascular remodeling imitating the histopathological changes observed in human PH (predominantly Group 1). Vascular remodeling in the pulmonary circulation results in the remodeling of the right ventricle (RV). The procedures for measuring RV pressures (using the open chest method), the morphometrical analyses of the RV (by dissecting and weighing both cardiac ventricles) and the histological assessments of the remodeling (both pulmonary by assessing vascular remodeling and cardiac by assessing RV cardiomyocyte hypertrophy and fibrosis) are described in detail. The advantages of this protocol are the possibility of the application both in wild type and in genetically modified mice, the relatively easy and low-cost implementation, and the quick development of the disease of interest (3 weeks). Limitations of this method are that mice do not develop a severe phenotype and PH is reversible upon return to normoxia. Prevention, as well as therapy studies, can easily be implemented in this model, without the necessity of advanced skills (as opposed to surgical rodent models).


Assuntos
Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Indóis/farmacologia , Pirróis/farmacologia , Animais , Hipóxia Celular/efeitos dos fármacos , Modelos Animais de Doenças , Fibrose , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Concentração de Íons de Hidrogênio , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/complicações , Masculino , Camundongos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Remodelação Vascular/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
10.
Clin Imaging ; 66: 147-152, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32531708

RESUMO

PURPOSE: We did a comparative analysis of matched and mismatched defects in pre- and post-operative V/Q scans in CTEPH patients. We correlated the number of these defects with pre-operative clinical and hemodynamic parameters. METHODS: This was a retrospective study on 27 patients with CTEPH who underwent surgery. Pre- and post-operative V/Q scans were graded for each lung segment as normal, matched or mismatched defect. Additional pre- and post-operative clinical and hemodynamic parameters that were collected include New York Heart Association functional class, six-minute walk distance in feet, N-terminal pro b-type natriuretic peptide, forced expiratory volume in one second/forced vital capacity, diffusing capacity of the lung for carbon monoxide, pulmonary arterial pressure (systolic, diastolic and mean), right atrial pressure, cardiac output and cardiac index. Pulmonary vascular resistance was then calculated. RESULTS: On a segmental basis, 176 mismatched defects were noted in 27 patients, of which 111 improved post-surgery (63%). 22 of the 34 matched defects improved following surgery (64%). 31 new mismatched defects were observed. The number of pre-operative matched defects per patient ranged from 0 to 6. No statistically significant associations were observed between the number of pre-operative matched defects and pre-operative clinical parameters. No statistically significant associations were observed between the number of improved matched defects and the change in clinical parameters (pre- to post-surgery). CONCLUSION: Both matched and mismatched defects on preoperative V/Q scans can show normalization post-surgery. The extent of matched defects on a preoperative V/Q scan does not correlate significantly with other clinical and hemodynamic parameters.


Assuntos
Hipertensão Pulmonar/diagnóstico por imagem , Cintilografia de Ventilação/Perfusão , Doença Crônica , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Embolia Pulmonar , Estudos Retrospectivos
11.
Vet Res Commun ; 44(2): 73-81, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32500313

RESUMO

BACKGROUND: Sildenafil improves autonomic dysfunction caused by pulmonary hypertension (PH) in humans, but its effect is unknown in dogs with PH. This prospective study aimed to evaluate the autonomic nervous system function of a canine model of chronic embolic PH (CEPH) and the autonomic nervous system function of a canine model of CEPH in which sildenafil was administered. METHODS: This study used five clinically healthy female beagle dogs. Evaluation parameters included hemodynamic parameters, heart rate (HR) and heart rate variability (HRV). Each evaluation parameter was compared before and after creating the CEPH model (before, BL; after, CEPHBL) and between the CEPHBL model and after the administration of sildenafil (1 mg/kg, BID) in the CEPH model dogs (CEPHSil). RESULTS: In the CEPHBL model, the hemodynamic parameters indicated cardiac hypofunction, and HR was significantly increased and HRV was significantly decreased compared with BL. Further, in the CEPHSil model, the hemodynamic parameters suggested improvement in cardiac function, and HRV was significantly increased. CONCLUSIONS: From the results of the CEPH model dogs, autonomic dysfunction was shown to occur in PH dogs. In addition, the administration of 1 mg/kg of sildenafil to CEPH model dogs may improve autonomic dysfunction.


Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/farmacologia , Animais , Sistema Nervoso Autônomo/fisiopatologia , Doença Crônica , Modelos Animais de Doenças , Cães , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/fisiopatologia
12.
PLoS One ; 15(5): e0233176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32421724

RESUMO

INTRODUCTION: Levosimendan is approved for acute heart failure. Within this context, pulmonary hypertension represents a frequent co-morbidity. Hence, the effects of levosimendan on segmental pulmonary vascular resistance (PVR) are relevant. So far, this issue has been not studied. Beyond that the relaxant effects of levosimendan in human pulmonary vessel are unknown. We addressed these topics in rats' isolated perfused lungs (IPL) and human precision-cut lung slices (PCLS). MATERIAL AND METHODS: In IPL, levosimendan (10 µM) was perfused in untreated and endothelin-1 pre-contracted lungs. The pulmonary arterial pressure (PPA) was continuously recorded and the capillary pressure (Pcap) was determined by the double-occlusion method. Thereafter, segmental PVR, expressed as precapillary (Rpre) and postcapillary resistance (Rpost) and PVR were calculated. Human PCLS were prepared from patients undergoing lobectomy. Levosimendan-induced relaxation was studied in naïve and endothelin-1 pre-contracted PAs and PVs. In endothelin-1 pre-contracted PAs, the role of K+-channels was studied by inhibition of KATP-channels (glibenclamide), BKCa2+-channels (iberiotoxin) and Kv-channels (4-aminopyridine). All changes of the vascular tone were measured by videomicroscopy. In addition, the increase of cAMP/GMP due to levosimendan was measured by ELISA. RESULTS: Levosimendan did not relax untreated lungs or naïve PAs and PVs. In IPL, levosimendan attenuated the endothelin-1 induced increase of PPA, PVR, Rpre and Rpost. In human PCLS, levosimendan relaxed pre-contracted PAs or PVs to 137% or 127%, respectively. In pre-contracted PAs, the relaxant effect of levosimendan was reduced, if KATP- and Kv-channels were inhibited. Further, levosimendan increased cGMP in PAs/PVs, but cAMP only in PVs. DISCUSSION: Levosimendan reduces rats' segmental PVR and relaxes human PAs or PVs, if the pulmonary vascular tone is enhanced by endothelin-1. Regarding levosimendan-induced relaxation, the activation of KATP- and Kv-channels is of impact, as well as the formation of cAMP and cGMP. In conclusion, our results suggest that levosimendan improves pulmonary haemodynamics, if PVR is increased as it is the case in pulmonary hypertension.


Assuntos
Hipertensão Pulmonar , Pulmão , Artéria Pulmonar , Veias Pulmonares , Simendana/farmacologia , Resistência Vascular/efeitos dos fármacos , Animais , Feminino , Humanos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Perfusão , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Veias Pulmonares/metabolismo , Veias Pulmonares/fisiopatologia , Ratos , Ratos Wistar
13.
J Cardiovasc Magn Reson ; 22(1): 28, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32354373

RESUMO

BACKGROUND: Pulmonary hypertension (PH) conveys a worse prognosis in heart failure (HF), in particular when right ventricular (RV) dysfunction ensues. Cardiovascular magnetic resonance (CMR) non-invasively estimates pulmonary vascular resistance (PVR), which has shown prognostic value in HF. Importantly, RV to pulmonary artery (PA) coupling is altered early in HF, before significant rise in PV resistance occurs. The aim of this study was to assess the prognostic value of mean velocity at the pulmonary artery (mvPA), a novel non-invasive parameter determined by CMR, in HF with reduced ejection fraction (HFrEF) with and without associated PH. METHODS: Prospective inclusion of 238 patients admitted for new-onset HFrEF. MvPA was measured with CMR during index admission. The primary endpoint was defined as a composite of HF readmissions and all-cause mortality. RESULTS: During a median follow-up of 25 months, 91 patients presented with the primary endpoint. Optimal cut-off value of mvPA calculated by the receiver operator curve for the prediction of the primary endpoint was 9 cm/s. The primary endpoint occurred more frequently in patients with mvPA≤9 cm/s, as indicated by Kaplan-Meier survival curves; Log Rank 16.0, p <  0.001. Importantly, mvPA maintained its prognostic value regardless of RV function and also when considering mortality and HF readmissions separately. On Cox proportional hazard analysis, reduced mvPA≤9 cm/s emerged as an independent prognostic marker, together with NYHA III-IV/IV class, stage 3-4 renal failure and ischemic cardiomyopathy. CONCLUSIONS: In our HFrEF cohort, mvPA emerged as an independent prognostic indicator independent of RV function, allowing identification of a higher-risk population before structural damage onset. Moreover, mvPA emerged as a surrogate marker of the RV-PA unit coupling status.


Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Artéria Pulmonar/diagnóstico por imagem , Volume Sistólico , Função Ventricular Esquerda , Idoso , Velocidade do Fluxo Sanguíneo , Progressão da Doença , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Artéria Pulmonar/fisiopatologia , Fatores de Risco , Fatores de Tempo , Função Ventricular Direita
14.
PLoS One ; 15(5): e0232544, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396557

RESUMO

This study examined the impact of septal flattening on left ventricular (LV) torsion in patients with precapillary pulmonary hypertension (PH). Fifty-two patients with proven precapillary PH and 13 healthy controls were included. Ventricular function was assessed including 4D-measurements, tissue velocity imaging, and speckle tracking analysis. Increased eccentricity index (1.39 vs. 1.08, p<0.001), systolic pulmonary artery pressure (64 vs. 29mmHg, p<0.001) and right ventricular Tei index (0.55 vs. 0.28, p = 0.007), and reduced tricuspid annular plane systolic excursion (19.0 vs. 26.5mm, p<0.001) were detected in PH patients as compared to controls. With increasing eccentricity of left ventricle, LV torsion was both decreased and delayed. Torsion rate paralleled this pattern of change during systole, but not during diastole. In conclusion, right ventricular pressure overload directly affects LV torsion mechanics. The echocardiographic methodology applied provides novel insights in the interrelation of right- and left ventricular function.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Direita/fisiologia , Pressão Ventricular/fisiologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Ecocardiografia , Humanos , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Torção Mecânica , Disfunção Ventricular Esquerda/etiologia
15.
Pediatr Cardiol ; 41(6): 1115-1124, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32388668

RESUMO

Elective closure of atrial septal defect (ASD) is usually recommended during preschool ages. However, ASD may contribute to deteriorating health in the presence of significant comorbidity and, thus, may need earlier closure. There is a lack of clarity regarding the indications for and outcomes after ASD closure in infancy and early childhood. We investigated the benefits and safety of surgical ASD closure in symptomatic patients under 2 years of age. Retrospective chart review was conducted in patients who underwent surgical ASD closure within the first 2 years of life. Of 31 symptomatic ASD patients, 22 had persistent respiratory symptoms, 24 failure to thrive, and 9 pulmonary hypertension. Overall, 26 patients (84.0%) showed clinical improvement after ASD closure, including improved respiratory status (17/22; 77.3%), resumption of normal growth (15/24; 62.5%), and resolution of pulmonary hypertension (7/7; 100%, 2 patients unable to assess postoperatively). Two medically complicated patients died a few months after surgery unrelated to surgical complications. Four out of 8 ventilator-dependent patients were weaned from mechanical ventilation within 1 month after ASD closure. Closure of ASD did not improve those patients with highly advanced lung disease and/or medically complex conditions including underlying genetic abnormalities. Surgical complications were uncommon. Postoperative hospital stay was 4 to 298 days (median 8 days). The majority of our patients demonstrated significant clinical improvement after ASD closure. Early ASD closure is safe and beneficial for symptomatic infants and young children with associated underlying pulmonary abnormalities, especially bronchopulmonary dysplasia.


Assuntos
Comunicação Interatrial/cirurgia , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/fisiopatologia , Cateterismo Cardíaco/métodos , Pré-Escolar , Feminino , Comunicação Interatrial/complicações , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/fisiopatologia , Lactente , Tempo de Internação , Masculino , Estudos Retrospectivos , Resultado do Tratamento
17.
Int J Cardiovasc Imaging ; 36(10): 1831-1843, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32462450

RESUMO

Noninvasive estimation of systolic pulmonary artery pressure (SPAP) during exercise stress echocardiography (ESE) is recommended for pulmonary hemodynamics evaluation but remains flow-dependent. Our aim was to assess the feasibility of pulmonary vascular reserve index (PVRI) estimation during ESE combining SPAP with cardiac output (CO) or exercise-time and compare its value in three group of patients: with invasively confirmed pulmonary hypertension (PH), at risk of PH development (PH risk) mainly with systemic sclerosis and in controls (C) without clinical risk factors for PH, age-matched with PH risk patients. We performed semisupine ESE in 171 subjects: 31 PH, 61 PH at risk and 50 controls as well as in 29 young, healthy normals. Rest and stress assessment included: tricuspid regurgitant flow velocity (TRV), pulmonary acceleration time (ACT), CO (Doppler-estimated). SPAP was calculated from TRV or ACT when TRV was not available. We estimated PVRI based on CO (peak CO/SPAP*0.1) or exercise-time (ESE time/SPAP*0.1). During stress, TRV was measurable in 44% patients ACT in 77%, either one in 95%. PVRI was feasible in 65% subjects with CO and 95% with exercise-time (p < 0.0001). PVRI was lower in PH compared to controls both for CO-based PVRI (group 1 = 1.0 ± 0.95 vs group 3 = 4.28 ± 2.3, p < 0.0001) or time-based PVRI estimation (0.66 ± 0.39 vs 3.95 ± 2.26, p < 0.0001). The proposed criteria for PH detection were for CO-based PVRI ≤ 1.29 and ESE-time based PVRI ≤ 1.0 and for PH risk ≤ 1.9 and ≤ 1.7 respectively. Noninvasive estimation of PVRI can be obtained in near all patients during ESE, without contrast administration, integrating TRV with ACT for SPAP assessment and using exercise time as a proxy of CO. These indices allow for comparison of pulmonary vascular dynamics in patients with varied exercise tolerance and clinical status.


Assuntos
Ecocardiografia Doppler , Ecocardiografia sob Estresse , Teste de Esforço , Hemodinâmica , Hipertensão Pulmonar/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Circulação Pulmonar , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Arterial , Débito Cardíaco , Estudos de Casos e Controles , Europa (Continente) , Tolerância ao Exercício , Estudos de Viabilidade , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Artéria Pulmonar/fisiopatologia , Fatores de Tempo , Adulto Jovem
18.
Int J Cardiovasc Imaging ; 36(8): 1497-1505, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32350704

RESUMO

Pulmonary hypertension (PH) is a well-recognised complication of sarcoidosis. Non-invasive diagnosis is challenging due to limited accuracy of echocardiography in interstitial lung disease. This study evaluates the value of echocardiographic PH probability for diagnosing PH in pulmonary sarcoidosis. All consecutive patients between August 2015 and November 2018 were prospectively screened for PH, and classified as low, intermediate or high PH probability. Patients with intermediate or high PH probability were referred for right heart catheterisation. PH was defined as a mean pulmonary artery pressure of ≥ 25 mm Hg. Additional data on pulmonary function and chest-CT was collected. Of all 479 patients, PH was present in 17 and absent in 19 patients. Six patients refused right heart catheterisation. PH was present in 33% and 75% of patients with intermediate and high PH probability respectively (n = 36). TRV max was measurable in 46% of all patients. Measurability did not correlate with FVC% predicted or presence of significant fibrosis. In intermediate and high PH probability, TRV max < 2.9 m/s successfully ruled out PH whereas a TRV max > 3.4 confirmed PH in all patients. If TRV max was absent or in between 2.9 and 3.4, secondary echocardiographic signs were not able to improve the diagnostic accuracy. PH is unlikely in patients with a TRV max < 2.9 m/s on echocardiography, whereas PH is highly suspected in a TRV max > 3.4 m/s. Discrimination is challenging if the TRV max is between 2.9-3.4 m/s or absent. Additional secondary signs do not improve discrimination. Decision making for further investigations should be made by an expert team.


Assuntos
Ecocardiografia , Hipertensão Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/diagnóstico por imagem , Adulto , Idoso , Pressão Arterial , Função do Átrio Direito , Progressão da Doença , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Fatores de Risco , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/fisiopatologia , Função Ventricular Direita
19.
Int J Cardiovasc Imaging ; 36(9): 1699-1709, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32440796

RESUMO

Measurement of pulmonary venous flow (PVF) parameters can be used to estimate left ventricular end-diastolic pressure (LVEDP) on transthoracic echocardiography. Despite that, 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) algorithm gave a secondary role to PVF to assess left ventricular filling pressure. We aimed to test correlations between several PVF parameters, including novel measurements, with LVEDP and to analyze whether PVF parameters have an incremental usefulness over ASE/EACVI algorithm to estimate LVEDP. Seventy-two patients that underwent left and right cardiac catheterization for assessment of heart failure or pulmonary hypertension were enrolled. All patients had a detailed echocardiographic study immediately before catheterization. Patients were categorized into those with an LVEDP < 15 mmHg vs. LVEDP ≥ 15 mmHg to analyze data. Patients with an elevated LVEDP had significantly lower peak S/D velocity ratio, S wave deceleration time, D wave acceleration time and D wave deceleration time (DWDT), as well as higher D wave acceleration rate (DWAR), but only peak S/D velocity ratio (ß = - 0.28, p = 0.01), DWDT (ß = - 0.33, p = 0.001) and DWAR (ß = 0.23, p = 0.03) were independent predictors for an elevated LVEDP. ASE/EACVI algorithm had a sensitivity of 71% and specificity of 74% to predict an elevated LVEDP. When PVF parameters were adjusted for ASE/EACVI algorithm; DWDT and DWAR remained as independent predictors. Sensitivity and specificity of ASE/EACVI algorithm increased to 79% and 96%, respectively, if either DWDT or DWAR was also suggestive of an elevated LVEDP. DWDT and DWAR have incremental usefulness over existing algorithm to determine LVEDP.


Assuntos
Ecocardiografia Doppler de Pulso , Insuficiência Cardíaca/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico por imagem , Circulação Pulmonar , Veias Pulmonares/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Pressão Ventricular , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Cateterismo Cardíaco , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Veias Pulmonares/fisiopatologia , Reprodutibilidade dos Testes , Disfunção Ventricular Esquerda/fisiopatologia
20.
Respir Med ; 167: 105966, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32421542

RESUMO

BACKGROUND: Macitentan treatment for chronic thromboembolic pulmonary hypertension (CTEPH) in the routine clinical setting is increasing. However, 'real world' macitentan experience is scarce and is needed to differentiate from controlled clinical trial settings. OBJECTIVE: We describe our outcomes and clinical 'real world' experience of macitentan mono- and combination therapy with riociguat or sildenafil in CTEPH. METHODS: We included all consecutive CTEPH patients, either non-operated or with residual PH after pulmonary endarterectomy (PEA), treated with macitentan in the St. Antonius hospital in Nieuwegein, the Netherlands, between 01-2014 and 11-2019. We describe clinical outcomes and adverse events (AEs) until 2 years after macitentan initiation. RESULTS: In total 73 CTEPH patients on macitentan were included, of which 18 patients were clinically inoperable (n = 7 declined PEA, n = 11 nonacceptable risk-benefit) and 55 had technically inoperable CTEPH (n = 48)/residual PH (n = 7). Clinically inoperable patients (mean age 72.4 ± 10.2 years, 61% female, 28% macitentan monotherapy, observation period 2.0 (1.9-2.0) years) had a survival of 100% and clinical worsening (CW)-free survival of 88% at 2-year follow-up respectively, with a significant increased 6-min walking distance (6MWD). Technically inoperable/residual PH patients (mean age 62.1 ± 14.1 years, 60% female, 27% macitentan monotherapy, observation period 2.0 (1.0-2.0) years) had a 2-year survival and CW-free survival of 86% and 68% respectively, with significant improved 6MWD and NT-proBNP. Nonsevere AEs were reported in 30% of all patients. CONCLUSION: Macitentan mono- and combination therapy in non-operated CTEPH and residual PH is safe and improves clinical outcomes till 2-year follow-up.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Embolia Pulmonar/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Embolia Pulmonar/mortalidade , Embolia Pulmonar/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Teste de Caminhada , Caminhada
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