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INTRODUCTION: Doppler-derived pulmonary pulse transit time (pPTT) is an auspicious hemodynamic marker in chronic pulmonary diseases. The aim is to compare four distinct pPTT measurements and its relation to right cardiac and pulmonary function. METHODS: Prospectively, 25 chronic obstructive pulmonary disease (COPD) patients (four patients excluded) and 32 healthy subjects underwent repeated distinct pPTT measurements, standard echocardiography, and pulmonary function testing on the same day. pPTT was defined as the interval from the R or Q-wave in the electrocardiogram to the corresponding pulse wave Doppler peak late systolic (S) 2 or diastolic (D) pulmonary vein flow velocity (pPTT R-S, Q-S, R-D, Q-D). Reproducibility was assessed using Bland-Altman analysis, coefficient of variation (COV), intraclass correlation coefficient (ICC), and power calculations. Associations with right ventricular RV tissue and pulse wave Doppler velocities (RV E', RV S', RV A', RV E, RV A, RV E/E', RV E/A), TAPSE, right ventricular fractional area change, left ventricular systolic and diastolic function (LV ejection fraction, E, A, E/A, E/E', septal E', lateral E'), LA diameters, as well as forced expiratory volume in 1 s, forced vital capacity (FVC) predicted (%), and in liters were analyzed. RESULTS: There was no significant difference and no bias between pPTT measures (p range: .1-.9). COV was in COPD 1.2%-2.3%, in healthy subjects 1.0%-3.1%. ICC ranged from .92 (COPD) to .96 (healthy subjects). In COPD significant correlations were found for pPTT R-S, Q-S and R-D with RV E`, (all > ρ: .49, < p = .0364), pPTT R-S, Q-S with RV E/E` (both > ρ: .49, < p = .0291), pPTT Q-S with RV S´ (ρ: .58, p = .0134), RV A (ρ: .59, p = .0339) and heart rate > ρ: -.39, < p = .0297). pPTT R-S, R-D showed significant correlations with FVC predicted (%) (ρ: .48 p = .0224) and FVC (l) (ρ:.47 p = .0347). CONCLUSIONS: All pPTT measures exhibited high reproducibility. In COPD patients pPTT measures correlate with diastolic right ventricular function. Defining Q as starting point seems clinically advantageous considering electromechanical desynchrony in patients with conduction disorders.
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Ecocardiografia Doppler , Doença Pulmonar Obstrutiva Crônica , Análise de Onda de Pulso , Humanos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Masculino , Feminino , Reprodutibilidade dos Testes , Análise de Onda de Pulso/métodos , Estudos Prospectivos , Ecocardiografia Doppler/métodos , Idoso , Pessoa de Meia-Idade , Testes de Função Respiratória/métodos , Velocidade do Fluxo Sanguíneo/fisiologiaRESUMO
Pulmonary vascular diseases such as pulmonary embolism and pulmonary hypertension are important and frequently under-recognised conditions. This article provides an overview of key highlights in pulmonary vascular diseases from the European Respiratory Society International Congress 2023. This includes insights into disease modification in pulmonary arterial hypertension and novel therapies such as sotatercept and seralutinib. Exciting developments in our understanding of the mechanisms underpinning pulmonary hypertension associated with interstitial lung disease are also explored. A comprehensive overview of the complex relationship between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) is provided along with our current understanding of the molecular determinants of CTEPH. The importance of multidisciplinary and holistic care cannot be understated, and this article also addresses advances beyond medication, with a special focus on exercise training and rehabilitation.
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A minimal diffusion barrier is key to the pulmonary gas exchange. In alveolar capillary dysplasia (ACD), a rare genetically driven disease of early infancy, this crucial fibrovascular interface is compromised while the underlying pathophysiology is insufficiently understood. Recent in-depth analyses of vascular alterations in adult lung disease encouraged researchers to extend these studies to ACD and compare the changes of the microvasculature. Lung tissue samples of children with ACD (n = 12), adults with non-specific interstitial pneumonia (n = 12), and controls (n = 20) were studied using transmission electron microscopy, single-gene sequencing, immunostaining, exome sequencing, and broad transcriptome profiling. In ACD, pulmonary capillary basement membranes were hypertrophied, thickened, and multilamellated. Transcriptome profiling revealed increased CDH5, COL4A1, COL15A1, PTK2B, and FN1 and decreased VIT expression, confirmed by immunohistochemistry. In contrast, non-specific interstitial pneumonia samples showed a regular basement membrane architecture with preserved VIT expression but also increased COL15A1+ vessels. This study provides insight into the ultrastructure and pathophysiology of ACD. The lack of normally developed lung capillaries appeared to cause a replacement by COL15A1+ vessels, a mechanism recently described in interstitial lung disease. The VIT loss and FN1 overexpression might contribute to the unique appearance of basement membranes in ACD. Future studies are needed to explore the therapeutic potential of down-regulating the expression of FN1 and balancing VIT deficiency.
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Doenças Pulmonares Intersticiais , Síndrome da Persistência do Padrão de Circulação Fetal , Recém-Nascido , Criança , Adulto , Humanos , Membrana Basal , Alvéolos Pulmonares , Pulmão , CapilaresRESUMO
BACKGROUND/AIMS: Conflicting results have been reported regarding the interaction between proton pump inhibitors (PPIs) and clopidogrel. We investigated whether concomitant PPI use influenced the risk of recurrence in patients with stroke and myocardial infarction (MI). METHODS: This study used two databases for two different designs, the Korean National Health Insurance Service (NHIS) database for a self-controlled case series design, and the national sample cohort of the NHIS data base converted to the Observational Medical Outcomes Partnership-Common Data Model version for a cohort study based on large-scale propensity score matching. RESULTS: In the PPI co-prescription group, recurrent hospitalization with stroke occurred in 17.6% of the 8201 patients with history of stroke, and recurrent MI occurred in 17.1% of the 1216 patients with history of MI within1 year. According to the self-controlled case series, the overall relative risk (RR) of recurrent stroke was 2.09 (95% confidence interval (CI); 1.83-2.38); the RR showed an increasing trend parallel to the time from the beginning of PPI co-prescription. In the cohort study, there was a higher incidence of recurrent stroke in the PPI co-prescription group (Hazard ratio (HR): 1.34, 95% CI: 1.01-1.76, p = 0.04). The overall RR of recurrent MI was 1.47 (95% CI; 1.02-2.11) in the self-controlled case series; however, there was no statistically significant difference in recurrent MI in the cohort study (HR:1.42, 95% CI:0.79-2.49, p = 0.23). The impact of individual PPIs on stroke and MI showed different patterns. CONCLUSIONS: A PPI co-prescription >4 weeks with clopidogrel was associated with hospitalization of recurrent stroke within 1 year of initial diagnosis; however, its association with recurrent MI remains inconclusive. The influence of individual PPIs should be clarified in the future.
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A sensitive and accurate analytical method was developed and validated to detect bambermycin, a commonly used antibiotic in animal feed and livestock. The presence of bambermycin residues in food products can pose health risks to consumers, emphasizing the need for a sensitive and accurate analytical method. A reversed-phase analytical column was utilized with a mobile phase comprising 0.005 mol/L ammonium acetate in 5% acetonitrile (A) and 0.005 mol/L ammonium acetate in 95% acetonitrile (B) to achieve effective chromatographic separation. Quantitative determination of bambermycin in various samples, including beef, pork, chicken, milk, eggs, flatfish, eel, and shrimp, was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry. Sample extraction involved a mixture of methanol and a 25% ammonium hydroxide solution, followed by low-temperature purification and phospholipid removal utilizing a Phree cartridge. The method exhibited a satisfactory recovery rate ranging from 69% to 100%. Validation results demonstrated the reliability, robustness, and accuracy of the method, exhibiting good linearity, precision, and recovery. This validated method can be applied for routine analysis of bambermycin residues, assisting in the development of effective monitoring and control measures to ensure the safety of livestock and aquatic products.
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Bambermicinas , Animais , Bovinos , Cromatografia Líquida de Alta Pressão/métodos , Gado , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Contaminação de Alimentos/análise , Inocuidade dos Alimentos , Acetonitrilas/química , Extração em Fase SólidaRESUMO
BACKGROUND: Among patients meeting diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH), there is an emerging lung phenotype characterised by a low diffusion capacity for carbon monoxide (DLCO) and a smoking history. The present study aimed at a detailed characterisation of these patients. METHODS: We analysed data from two European pulmonary hypertension registries, COMPERA (launched in 2007) and ASPIRE (from 2001 onwards), to identify patients diagnosed with IPAH and a lung phenotype defined by a DLCO of less than 45% predicted and a smoking history. We compared patient characteristics, response to therapy, and survival of these patients to patients with classical IPAH (defined by the absence of cardiopulmonary comorbidities and a DLCO of 45% or more predicted) and patients with pulmonary hypertension due to lung disease (group 3 pulmonary hypertension). FINDINGS: The analysis included 128 (COMPERA) and 185 (ASPIRE) patients with classical IPAH, 268 (COMPERA) and 139 (ASPIRE) patients with IPAH and a lung phenotype, and 910 (COMPERA) and 375 (ASPIRE) patients with pulmonary hypertension due to lung disease. Most patients with IPAH and a lung phenotype had normal or near normal spirometry, a severe reduction in DLCO, with the majority having no or a mild degree of parenchymal lung involvement on chest computed tomography. Patients with IPAH and a lung phenotype (median age, 72 years [IQR 65-78] in COMPERA and 71 years [65-76] in ASPIRE) and patients with group 3 pulmonary hypertension (median age 71 years [65-77] in COMPERA and 69 years [63-74] in ASPIRE) were older than those with classical IPAH (median age, 45 years [32-60] in COMPERA and 52 years [38-64] in ASPIRE; p<0·0001 for IPAH with a lung phenotype vs classical IPAH in both registries). While 99 (77%) patients in COMPERA and 133 (72%) patients in ASPIRE with classical IPAH were female, there was a lower proportion of female patients in the IPAH and a lung phenotype cohort (95 [35%] COMPERA; 75 [54%] ASPIRE), which was similar to group 3 pulmonary hypertension (336 [37%] COMPERA; 148 [39%] ASPIRE]). Response to pulmonary arterial hypertension therapies at first follow-up was available from COMPERA. Improvements in WHO functional class were observed in 54% of patients with classical IPAH, 26% of patients with IPAH with a lung phenotype, and 22% of patients with group 3 pulmonary hypertension (p<0·0001 for classical IPAH vs IPAH and a lung phenotype, and p=0·194 for IPAH and a lung phenotype vs group 3 pulmonary hypertension); median improvements in 6 min walking distance were 63 m, 25 m, and 23 m for these cohorts respectively (p=0·0015 for classical IPAH vs IPAH and a lung phenotype, and p=0·64 for IPAH and a lung phenotype vs group 3 pulmonary hypertension), and median reductions in N-terminal-pro-brain-natriuretic-peptide were 58%, 27%, and 16% respectively (p=0·0043 for classical IPAH vs IPAH and a lung phenotype, and p=0·14 for IPAH and a lung phenotype vs group 3 pulmonary hypertension). In both registries, survival of patients with IPAH and a lung phenotype (1 year, 89% in COMPERA and 79% in ASPIRE; 5 years, 31% in COMPERA and 21% in ASPIRE) and group 3 pulmonary hypertension (1 year, 78% in COMPERA and 64% in ASPIRE; 5 years, 26% in COMPERA and 18% in ASPIRE) was worse than survival of patients with classical IPAH (1 year, 95% in COMPERA and 98% in ASPIRE; 5 years, 84% in COMPERA and 80% in ASPIRE; p<0·0001 for IPAH with a lung phenotype vs classical IPAH in both registries). INTERPRETATION: A cohort of patients meeting diagnostic criteria for IPAH with a distinct, presumably smoking-related form of pulmonary hypertension accompanied by a low DLCO, resemble patients with pulmonary hypertension due to lung disease rather than classical IPAH. These observations have pathogenetic, diagnostic, and therapeutic implications, which require further exploration. FUNDING: COMPERA is funded by unrestricted grants from Acceleron, Bayer, GlaxoSmithKline, Janssen, and OMT. The ASPIRE Registry is supported by Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
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Hipertensão Pulmonar , Monóxido de Carbono/uso terapêutico , Hipertensão Pulmonar Primária Familiar , Feminino , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Peptídeos/uso terapêutico , Prognóstico , Sistema de RegistrosRESUMO
Alveolar capillary dysplasia (ACD) is a rare lung developmental disorder leading to persistent pulmonary arterial hypertension and fatal outcomes in newborns. The current study analyzed the microvascular morphology and the underlying molecular background of ACD. One ACD group (n = 7), one pulmonary arterial hypertension group (n = 20), and one healthy con1trol group (n = 16) were generated. Samples of histologically confirmed ACD were examined by exome sequencing and array-based comparative genomic hybridization. Vascular morphology was analyzed using scanning electron microscopy of microvascular corrosion casts. Gene expression and biological pathways were analyzed using two panels on inflammation/kinase-specific genes and a comparison analysis tool. Compartment-specific protein expression was analyzed using immunostaining. In ACD, there was an altered capillary network, a high prevalence of intussusceptive angiogenesis, and increased activity of C-X-C motif chemokine receptor 4 (CXCR4), hypoxia-inducible factor 1α (HIF1A), and angiopoietin signaling pathways compared with pulmonary arterial hypertension/healthy controls. Histologically, there was a markedly increased prevalence of endothelial tyrosine kinase receptor (TEK/TIE2)+ macrophages in ACD, compared with the other groups, whereas the CXCR4 ligand CXCL12 and HIF1A showed high expression in all groups. ACD is characterized by dysfunctional capillaries and a high prevalence of intussusceptive angiogenesis. The results indicate that endothelial CXCR4, HIF1A, and angiopoietin signaling as well as TIE2+ macrophages are crucial for the induction of intussusceptive angiogenesis and vascular remodeling. Future studies should address the use of anti-angiogenic agents in ACD, where TIE2 appears as a promising target.
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Síndrome da Persistência do Padrão de Circulação Fetal , Hipertensão Arterial Pulmonar , Angiopoietinas , Hibridização Genômica Comparativa , Humanos , Recém-Nascido , Síndrome da Persistência do Padrão de Circulação Fetal/patologia , Alvéolos Pulmonares/anormalidadesRESUMO
BACKGROUND AND AIM: Association between protonpump inhibitors (PPIs) and osteoporosis, hip fractures has not been fully elucidated. We aimed to evaluate the relationship between PPIs use and the risk of osteoporosis and hip fractures in the databases converted to a common data model (CDM) and to compare the results across the databases. METHODS: This was a population-based, propensity-matched, retrospective cohort study that included patients aged ≥ 50 years who were prescribed with PPIs for over 180 days. We compared the incidence of osteoporosis and hip fractures between new PPI user and new user of other drugs using the Cox proportional hazards model and performed meta-analysis in the electronic health record (EHR) databases. RESULTS: In the Korean National Health Insurance Service (NHIS)-CDM database, long-term PPI users had greater risk of osteoporosis [PPIs vs non-PPIs groups, 28.42/1000 person-years vs 19.29/1000 person-years; hazard ratio (HR), 1.62; 95% confidence interval (CI), 1.22-2.15; P = 0.001]. The meta-analytic results of six EHR databases also showed similar result (pooled HR, 1.57; 95% CI, 1.28-1.92). In the analysis of hip fracture, PPI use was not significantly associated with a hip fracture in the NHIS-CDM database (PPI vs non-PPI groups, 3.09/1000 person-years vs 2.26/1000 person-years; HR, 1.45; 95% CI, 0.74-2.80; P = 0.27). However, in the meta-analysis of four EHR databases, the risk of hip fractures was higher in PPI users (pooled HR, 1.82; 95% CI, 1.04-3.19). CONCLUSIONS: Long-term PPI was significantly associated with osteoporosis; however, the results of hip fractures were inconsistent. Further study based on better data quality may be needed.
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Fraturas do Quadril , Osteoporose , Estudos de Coortes , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Humanos , Estudos Multicêntricos como Assunto , Osteoporose/induzido quimicamente , Osteoporose/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: The prevalence of mental disorders, particularly adjustment disorder (AD), major depressive disorder (MDD) and panic disorder (PD) is increased in patients with pulmonary arterial hypertension (PAH). However, it is unclear which pathogenic mechanisms determine their development and could therefore be targeted in prevention or therapeutic interventions. Here, we assessed metacognitions in a sample of PAH patients with and without MDD and PD. Moreover, we reconstructed the course of mental illnesses following the PAH diagnosis. Methods: Two hundred seventeen PAH patients were included in this cross-sectional study. The prevalence of AD was assessed retrospectively using DSM-V criteria. Current mental disorders were assessed using the structured clinical interview for DSM-V. Additionally, metacognitive beliefs and processes were assessed using established questionnaires (MCQ-30, AnTI). Results: Patients with an AD consecutive to the PAH diagnosis more frequently developed MDD (37.5 vs. 13.9%, p < 0.001) and PD (26.3 vs. 8.8%, p = 0.001) later on compared to PAH patients without a former AD. Moreover, patients with current MDD/PD displayed more dysfunctional metacognitions than those without current MDD/PD (p < 0.001). Patients with current MDD/PD in the context of former AD had more dysfunctional metacognitive worries and beliefs compared to patients with current MDD/PD without former AD (p = 0.009). Conclusion: Our results suggest that in the context of PAH, dysfunctional metacognitions are associated with MDD and PD. Therefore, a metacognitive approach to treat and prevent those mental illnesses seems promising and should be investigated in future studies.
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Background: Mental disorders are common among patients with severe cardiovascular diseases (CVD). Yet, there is a lack of easily accessible evidence-based treatments. Recent research indicates elevated prevalence of dysfunctional metacognitions in patients with mental disorders following cardiovascular events. As metacognitive therapy (MCT) is an established treatment to modify metacognitions, we tested if a brief metacognitive intervention via videotelephony is effective in this patient group. Methods: A brief MCT treatment was tailored to CVD patients and designed as a face-to-face internet-based intervention. Five patients with CVDs and comorbid mental disorders underwent a psychocardiological examination and diagnostic approach. Each patient participated in eight 50 min sessions via encrypted video messenger service. Metacognitions, depression and anxiety symptoms and quality of life were assessed by self-report measures pre- and post-treatment. Patients rated dysfunctional thought processes, current psychological impairment, and treatment satisfaction after each session. Intended follow-up measures were not reported due to missing data. Results: For most patients, the brief metacognitive intervention was associated with a decrease in dysfunctional metacognitions and a reduction of symptoms of anxiety and depression post-treatment. Psychological and physiological quality of life improved. Patients reported high satisfaction with the tailored treatment. Conclusion: Our results suggest that a brief internet-based metacognitive treatment may be a promising tool for patients with CVDs and comorbid mental disorders. Feasibility and acceptance of the intervention was rated high by the patients. Further research is necessary to support the preliminary findings and to adapt and evaluate the intervention in a controlled clinical trial setting.
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Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially life-threatening condition associated with high morbidity and mortality. However, advances in medical, surgical and interventional treatment have markedly improved the outcome of patients with CTEPH. Additional factors potentially influencing quality of life (QoL) and outcome in CTEPH are yet to be defined. Child maltreatment is a major risk factor for unfavorable behavioral, mental as well as physical health outcomes and has been associated with decreased QoL. To date, no study assessed the impact of childhood trauma in patients with CTEPH. Methods: Patients with CTEPH were invited to complete the Childhood Trauma Questionnaire (CTQ). Data were compared to prevalence data from the German population. Mental well-being was assessed using the Hospital Anxiety and Depression Scale (HADS) and quality of life was measured using the WHO Quality of Life Questionnaire (WHOQOL). Furthermore, lifestyle factors and physical health parameters were studied.Logistic regression analysis was used to investigate a possible impact of child maltreatment on markers of disease severity. Results: One-hundred and seven patients with CTEPH completed the CTQ. These patients reported higher rates of emotional abuse and physical abuse and emotional neglect compared to the German population while rates of physical neglect and sexual abuse did not differ between patients and German population with prevalence of 20.6% for emotional abuse, 20% for physical abuse, 22% for emotional neglect, 46% for physical neglect, and 6% for sexual abuse in patients with CTEPH. Higher CTQ scores were associated with anxiety symptoms as well as negatively associated with QoL. No direct impact of childhood trauma on CTEPH severity was found. Conclusion: We found a higher rate of child maltreatment in patients with CTEPH in comparison to the German population. Correlations suggest moderate associations between CTQ scores and mental health and QoL. Child maltreatment had no significant impact on disease severity. Further investigation on proper interventions to support affected patients is needed.
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Introduction: Mental disorders are common in patients with pulmonary arterial hypertension (PAH) and contribute to impaired quality of life (QoL). The impact of mental disorders on access to health care, differences in clinical parameters and treatment in patients with PAH is unclear. In this study we sought to assess the impact of mental disorders and other health disparities on health-care-utilization in patients with PAH. Methods: In a cross-sectional observational study of patients with PAH, mental disorders were characterized using a structed clinical interview. In addition, patients completed a self-administered questionnaire to assess QoL, symptoms of anxiety and depression, lifestyle-factors and educational status. Number of outpatient visits and communication events per year were calculated as a surrogate for health-care-utilization and were compared by the presence of mental disorder. Linear regression analysis was conducted to assess the impact on health-care-utilization. Results: 117 patients with PAH participated in this study (70% female, median age 59 (interquartile range, 49-70) years). Significant differences between patients with or without mental disorders were found in anxiety, depression and QoL. There were no significant differences in clinical parameters. Patients with mental disorders had higher rates of outpatient visits and communication events than patients without mental disorders. Linear regression revealed a gain of 2.2 communication events per year in the presence of any mental disorders. Conclusion: Mental disorders in patients with PAH are common and significantly affect health-care-utilization. This higher demand in patients with mental disorder needs to be addressed by physicians, psychiatrists and specialized nurses offering therapeutic strategies.
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Objective: Pulmonary hypertension (PH) is a chronic and progressive pulmonary vascular disease resulting in symptoms such as shortness of breath and fatigue and leading to death from right heart failure if not adequately treated. Chronic thromboembolic pulmonary hypertension (CTEPH) is a subgroup of PH characterized by obstruction or occlusion of pulmonary arteries by post-embolic fibrotic material. To date, few studies examined symptoms of depression and anxiety in patients with CTEPH, showing depression levels as high as 37.5%. However, none of the former studies used structured expert interviews. Methods: Mental disorders were diagnosed using the Structured Clinical Interview for DSM-5 (SCID). The prevalence of mental disorders in patients with CTEPH were compared to the prevalence in patients with pulmonary arterial hypertension (PAH) and the general German population. Quality of life (QoL) was measured with World Health Organization (WHO) Quality of Life questionnaire (short form). Factors associated with QoL were analyzed with linear regression and the diagnostic value of the Hospital Anxiety and Depression Scale (HADS) was evaluated using receiver operating characteristics (ROC) curve analysis. Results: Hundred and seven patients with CTEPH were included. Almost one-third of the patients (31.8%) had current psychological disorders. Panic disorder (8.4%), specific phobia (8.4%), and major depressive disorder (6.5%) were the most prevalent mental illnesses. The prevalence of panic disorders was higher in CTEPH compared to the German population while major depressive disorder was fewer in CTEPH compared to PAH. The presence of mental disorders had a major impact on QoL. Hospital Anxiety and Depression Scale discriminated depression and panic disorder reliably. Conclusion: Mental disorders are common in patients with CTEPH and associated with an impaired QoL. The HADS may be a useful screening tool for panic and depression disorders in patients with CTEPH. Further research on therapeutic strategies targeting mental disorders in patients with CTEPH is needed.
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BACKGROUND/OBJECTIVE: Child maltreatment is associated with increased risk of psychological consequences, contributes to morbidity and has long lasting effects on mental health and quality of life. Child maltreatment has not been assessed in patients with pulmonary arterial hypertension (PAH). We examined the prevalence of child maltreatment and determined their impact on disease severity in patients with PAH. METHODS: A cross-sectional observational multicenter study at two PH centers in Germany was conducted. Patients with a confirmed diagnosis of PAH were given a self-administered questionnaire. Child maltreatment using the Childhood Trauma Questionnaire (CTQ), quality of life (QoL), anxiety, depression, and lifestyle factors were assessed and enhanced by clinical parameters 6-min walk distance (6MWD), WHO functional class (WHO FC), and serum levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). Prevalence rates of child maltreatment were compared to the general population and impact of child maltreatment on disease severity was calculated by logistic regression analysis. RESULTS: Two-hundred and seventeen patients, 71% female and a median age of 56 years were enrolled in this study. Patients with PAH had higher rates of emotional abuse and lower rates of physical neglect compared to the German population while rates of emotional neglect, physical abuse, and sexual abuse did not differ between patients and German population. Patients with any form of child maltreatment were more likely to be active smokers, had a worse QoL and more anxiety or depression. Moderate associations between child maltreatment, mental health, QoL, lifestyle factors and clinical parameters could be observed. Logistic regression analysis showed a significant impact of CTQ-total score on disease severity with an OR of 1.022 (95%-CI: 1.001-1.042, p = 0.035). CONCLUSION: We found a higher rate of child maltreatment in patients with PAH in comparison to the German population. Correlations suggest moderate associations between CTQ-scores and mental health as well as QoL. Child maltreatment had significant impact on disease severity. However, effects were moderate. We conclude that child maltreatment has effects on mental health and quality of life in patients with PAH and may have limited effect on disease severity.
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BACKGROUND: Since 2015, the European pulmonary hypertension guidelines recommend the use of combination therapy in most patients with pulmonary arterial hypertension (PAH). However, it is unclear to what extent this treatment strategy is adopted in clinical practice and if it is associated with improved long-term survival. METHODS: We analysed data from COMPERA, a large European pulmonary hypertension registry, to assess temporal trends in the use of combination therapy and survival of patients with newly diagnosed PAH between 2010 and 2019. For survival analyses, we looked at annualised data and at cumulated data comparing the periods 2010-2014 and 2015-2019. RESULTS: A total of 2531 patients were included. The use of early combination therapy (within 3â months after diagnosis) increased from 10.0% in patients diagnosed with PAH in 2010 to 25.0% in patients diagnosed with PAH in 2019. The proportion of patients receiving combination therapy 1â year after diagnosis increased from 27.7% to 46.3%. When comparing the 2010-2014 and 2015-2019 periods, 1-year survival estimates were similar (89.0% (95% CI 87.2-90.9%) and 90.8% (95% CI 89.3-92.4%), respectively), whereas there was a slight but nonsignificant improvement in 3-year survival estimates (67.8% (95% CI 65.0-70.8%) and 70.5% (95% CI 67.8-73.4%), respectively). CONCLUSIONS: The use of combination therapy increased from 2010 to 2019, but most patients still received monotherapy. Survival rates at 1â year after diagnosis did not change over time. Future studies need to determine if the observed trend suggesting improved 3-year survival rates can be confirmed.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Hipertensão Pulmonar Primária Familiar , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/epidemiologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/epidemiologia , Sistema de Registros , Taxa de SobrevidaRESUMO
BACKGROUND: Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a three-stratum model to categorise risk as low, intermediate or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on four risk categories, with intermediate risk subdivided into intermediate-low and intermediate-high risk. METHODS: We analysed data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on World Health Organization functional class, 6-min walk distance (6MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed using Kaplan-Meier analyses, log-rank testing and Cox proportional hazards models. RESULTS: Data from 1655 patients with PAH were analysed. Using the three-stratum model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined four-stratum risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the three-stratum model and in 49.2% with the four-stratum model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk. CONCLUSIONS: Modified risk stratification using a four-stratum model based on refined cut-off levels for functional class, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original three-stratum model.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Hipertensão Pulmonar Primária Familiar , Humanos , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Hipertensão Arterial Pulmonar/diagnóstico , Sistema de Registros , Medição de RiscoRESUMO
Background/Objective: Covid-19 pandemic may affect mental health and quality of life (QoL) in patients with pulmonary arterial hypertension (PAH). We assessed changes in anxiety and depression, quality of life (QoL) and self-described impact of Covid-19 in patients with PAH during the Covid-19 pandemic. Methods: This study included 152 patients with PAH from two German referral centers. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) at two different timepoints before and during the Covid-19 pandemic with a median of 232 days between baseline and follow-up. QoL was assessed using EQ-5D and emPHasis-10. Perceived impact of Covid-19 and related regulations and measures were assessed using a set of specific questions and statements. Results: More than two thirds of patients had an unsuspicious HADS-A and HADS-D. Median scores did not differ from baseline for both HADS-A and HADS-D (p = 0.202; p = 0.621). Overall, no significant changes in HADS-A or HADS-D categories from baseline to follow up were observed (p = 0.07; p = 0.13). QoL did not change between baseline and follow-up. The Covid-19 pandemic had little impact on access to medical care and established PAH therapy. Patients were in agreement with governmental measures and regulations and felt sufficiently safe. Conclusion: First waves of Covid-19 pandemic had little impact on anxiety, depression and QoL in patient with PAH. Established PAH therapy and access to medical care were not affected. Further studies on the impact of prolonged duration of the ongoing Covid-19 pandemic are needed.