RESUMEN
OBJECTIVE: The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events. METHODS: STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated. RESULTS: A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2 ± 9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr < 33.45% had more adverse long-term outcomes (log rank p < .0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p = .010). CONCLUSION: Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis.
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Ecocardiografía , Atrios Cardíacos , Lupus Eritematoso Sistémico , Humanos , Femenino , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Pronóstico , Ecocardiografía/métodos , Persona de Mediana Edad , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/sangre , Función del Atrio Derecho/fisiología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/etiología , Estudios de SeguimientoRESUMEN
OBJECTIVE: This study aims to assess the tricuspid annular plane systolic excursion (TAPSE)/PASP ratio as a potential indicator for predicting the probability of developing pulmonary arterial hypertension (PAH) in hyperthyroidism patients. A nomogram model will be developed based on our findings, as well as the receiver operating characteristic (ROC) curve. METHODS: The study involved 166 hyperthyroid patients treated at Yijishan Hospital, and the period covered August 2021 to August 2022. Patients were divided into two groups according to pulmonary artery systolic pressure ≥35 mmHg. Univariate and multivariate logistic analyses were performed on the two groups' demographic and laboratory data to identify potential diagnostic markers. These parameters were evaluated using ROC curves to determine their precision in forecasting PAH. The findings were validated by plotting a calibration curve based on a line chart model. RESULTS: In the study, eventually, 80 patients were enrolled: 30 in the PAH group and 50 in the No PAH group. Multipleistic regression analysis predicted the occurrence risk of developing PAH. When paired with other conventional echocardiographic parameters (such as TAPSE, MPI, and SV) and serological markers (such as FT3 and FT4), the developed model demonstrated outstanding predictive performance with an area under the ROC curve of 0.985, a Youden index of 0.971, a sensitivity of 100%, and a specificity of 97.1%. CONCLUSIONS: The nomogram model constructed by combining the TAPSE/PASP ratio with FT3 and FT4 serum markers, as well as conventional ultrasound parameters SV and MPI in hyperthyroidism patients, demonstrates robust discriminatory ability and consistency.
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Hipertiroidismo , Humanos , Hipertiroidismo/complicaciones , Hipertiroidismo/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Ecocardiografía/métodos , Adulto , Nomogramas , Valor Predictivo de las Pruebas , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico , Curva ROC , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/fisiopatología , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Medición de Riesgo/métodosRESUMEN
Arrhythmias are increasingly recognized as severe complications of precapillary pulmonary hypertension, encompassing pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Despite their significant contribution to symptoms, morbidity, in-hospital mortality, and potentially sudden death in PAH/CTEPH, there remains a lack of comprehensive data on epidemiology, pathophysiology, and outcomes to inform the management of these patients. This review provides an overview of the latest evidence on this subject, spanning from the molecular mechanisms underlying arrhythmias in the hypertrophied or failing right heart to the clinical aspects of epidemiology, diagnosis, and treatment.
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Arritmias Cardíacas , Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/complicaciones , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/complicaciones , Enfermedad Crónica , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicacionesRESUMEN
BACKGROUND: Accurately stratifying patients with pulmonary arterial hypertension (PAH) is very important, and traditional risk scores still have internal heterogeneity. This study aimed to construct a risk stratification model that can accurately identify clinical worsening (CW) events in conventional low-intermediate risk patients with pulmonary hypertension under targeted drug treatment by using echocardiographic parameters. METHODS: This study is a single-center, prospective study, including 105 PAH patients who underwent regular follow-up at Guangdong Provincial People's Hospital from October 2021 to April 2023. The primary endpoint was the occurrence of CW, including death, hospitalization due to pulmonary hypertension, escalation of targeted drug therapy, and worsening of PAH. The predictive value of the echocardiography-based three-strata risk model was assessed using Kaplan-Meier curves and COX regression analysis. RESULTS: A total of 98 PAH patients were ultimately included in this study. The median follow-up duration was 26 months (range 7-28 months). The echocardiography-based three-strata model included the ratio of tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (TAPSE/PASP) and inferior vena cava (IVC). The echocardiography-based three-strata model had higher diagnostic value (C-index = .76) compared to the 2022 ESC/ERS three-strata model and four-strata model (C-index = .66 and C-index = .61, respectively). PAH patients with lower TAPSE/PASP and wider IVC showed a higher CW rate compared to patients with higher TAPSE/PASP and normal IVC (HR = 15.1, 95%CI:4.4-51.9, p < .001). CONCLUSION: The echocardiography-based three-strata model based on TAPSE/PASP and IVC can effectively improve the stratification of low-intermediate risk PAH patients under targeted treatment.
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Ecocardiografía , Ventrículos Cardíacos , Arteria Pulmonar , Vena Cava Inferior , Humanos , Masculino , Femenino , Ecocardiografía/métodos , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/fisiopatología , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Estudios de SeguimientoAsunto(s)
Pulmón , Humanos , Pulmón/diagnóstico por imagen , Ultrasonografía/métodos , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Edema Pulmonar/etiología , Edema Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/diagnóstico por imagenRESUMEN
BACKGROUND: The consequences of tricuspid regurgitation (TR) for right ventricular (RV) function and prognosis in pulmonary arterial hypertension (PAH) are poorly described and effects of tricuspid valve repair on the RV are difficult to predict. METHODS: In 92 PAH patients with available cardiac magnetic resonance (CMR) studies, TR volume was calculated as the difference between RV stroke volume and forward stroke volume, i.e. pulmonary artery (PA) stroke volume. Survival was estimated from the time of the CMR scan to cardiopulmonary death or lung transplantation. In a subgroup, pressure-volume loop analysis including two-parallel elastances was applied to evaluate effective elastances, including net afterload (effective arterial elastance (E a)), forward afterload (effective pulmonary arterial elastance (E pa)) and backward afterload (effective tricuspid regurgitant elastance (E TR)). The effects of tricuspid valve repair were simulated using the online software package Harvi. RESULTS: 26% of PAH patients had a TR volume ≥30â mL. Greater TR volume was associated with increased N-terminal pro-brain natriuretic peptide (p=0.018), mean right atrial pressure (p<0.001) and RV end-systolic and -diastolic volume (both p<0.001). TR volume ≥30â mL was associated with a poor event-free survival (p=0.008). In comparison to E a, E pa correlated better with indices of RV dysfunction. Lower end-systolic elastance (E es) (p=0.002) and E TR (p=0.030), higher E pa (p=0.001) and reduced E es/E pa (p<0.001) were found in patients with a greater TR volume. Simulations predicted that tricuspid valve repair increases RV myocardial oxygen consumption in PAH patients with severe TR and low E es unless aggressive volume reduction is accomplished. CONCLUSIONS: In PAH, TR has prognostic significance and is associated with low RV contractility and RV-PA uncoupling. However, haemodynamic simulations showed detrimental consequences of tricuspid valve repair in PAH patients with low RV contractility.
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Hipertensión Arterial Pulmonar , Insuficiencia de la Válvula Tricúspide , Función Ventricular Derecha , Humanos , Insuficiencia de la Válvula Tricúspide/fisiopatología , Insuficiencia de la Válvula Tricúspide/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Volumen Sistólico , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Pronóstico , Anciano , Válvula Tricúspide/fisiopatología , Válvula Tricúspide/diagnóstico por imagen , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/diagnóstico por imagen , Imagen por Resonancia Magnética , Hipertensión Pulmonar/fisiopatología , Péptido Natriurético Encefálico/sangreRESUMEN
BACKGROUND: Portopulmonary hypertension (PoPH), associated with increased mortality, can limit treatment options for liver diseases. Data on the continuum of clinical risk related to cardiopulmonary hemodynamics in PoPH are lacking. METHODS AND RESULTS: As part of the United States national Veterans Affairs Clinical Assessment, Reporting, and Tracking database, we performed a retrospective cohort study of adults with cirrhosis undergoing right heart catheterization between October 1, 2017, and September 30, 2022. Pulmonary hypertension (mean pulmonary arterial pressure [mPAP] >20 mm Hg without PoPH) and PoPH (mPAP >20 mm Hg+pulmonary artery wedge pressure ≤15 mm Hg+pulmonary vascular resistance ≥3 WU) were defined by right heart catheterization hemodynamics. Multivariable Cox proportional hazards using natural splines for hemodynamic variables were used to evaluate the association between cardiopulmonary hemodynamics and mortality following right heart catheterization. A total of 4409 patients were included in the final analysis, predominantly men (96.3%), with a mean age of 68.5 years. Pulmonary hypertension and PoPH were observed in 71.6% and 10.2% of the cohort, respectively. Compared with a reference cardiac index of 2.5 L/min per m2, the hazard for mortality increased progressively with decreasing cardiac index, even after adjustment for mPAP and pulmonary vascular resistance. The minority of patients with PoPH (N=65, 14.5%) were prescribed pulmonary vasodilator therapy. CONCLUSIONS: These data suggest that pulmonary hypertension and PoPH are prevalent in veterans with chronic liver disease, but low use of targeted PoPH therapy persists. Cardiac function discriminated mortality risk across a wide range of mPAP and pulmonary vascular resistance values and may diagnose and clarify prognosis in this patient population.
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Hipertensión Portal , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Veteranos , Masculino , Adulto , Humanos , Anciano , Femenino , Estudios Retrospectivos , Hipertensión Portal/complicaciones , Hipertensión Portal/terapia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Hemodinámica , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/complicacionesAsunto(s)
Enfermedades del Tejido Conjuntivo , Hipertensión Arterial Pulmonar , Humanos , Enfermedades del Tejido Conjuntivo/complicaciones , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatologíaRESUMEN
Pulmonary arterial hypertension (PAH) is a common complication of systemic lupus erythematosus (SLE), and PAH can cause right ventricle (RV) remodel and dyssynchrony. The aim of this study was to explore the value of RV dyssynchrony in predicting adverse clinical events in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension (SLE-PAH) using two-dimensional speckle tracking echocardiography (2D-STE). A total of 53 patients with SLE-PAH were enrolled in this study. The dyssynchrony of the RV (RV-SD6) was evaluated by 2D-STE. The clinical data of all participants were collected, and routine cardiac function parameters were measured by two-dimensional echocardiography, and analyzed for their correlation with RV-SD6. The predictive value of RV-SD6 in clinical adverse event was evaluated. RV-SD6 was negatively correlated with RV-FLS, RV-FAC, and TAPSE (r = - 0.788, r = - 0.363 and r = - 0.325, respectively, all P < 0.01), while the correlation with RV-FLS was the strongest. linear regression analysis showed that RV-FLS was an independent risk factor for RV-SD6 (ß = - 1.40, 95% CI - 1.65 ~ - 1.14, P < 0.001). Cox regression analysis showed that RV-SD6 was a predictor with clinical adverse events (HR = 1.03, 95% CI 1 ~ 1.06, P < 0.05). RV-SD6 was highly discriminative in predicting clinical adverse events (AUC = 0.764), at a cutoff of 51.10 ms with a sensitivity of 83.3% and specificity of 68.3%. RV-FLS was negatively correlated with RV-SD6 and was an independent risk factor for it. RV-SD6 can serve as an indicator for predicting the occurrence of adverse clinical events in SLE-PAH patients, with high sensitivity and specificity.
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Lupus Eritematoso Sistémico , Valor Predictivo de las Pruebas , Hipertensión Arterial Pulmonar , Disfunción Ventricular Derecha , Función Ventricular Derecha , Humanos , Femenino , Masculino , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/etiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Adulto , Persona de Mediana Edad , Pronóstico , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Arterial Pulmonar/diagnóstico , Factores de Riesgo , Ecocardiografía , Reproducibilidad de los Resultados , Medición de Riesgo , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/diagnóstico por imagen , Remodelación VentricularRESUMEN
Pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with left-sided heart and lung diseases are most commonly easily discriminated and treated accordingly. With the changing epidemiology of PAH, however, a growing proportion of patients at the time of diagnosis present with comorbidities of varying severity. In addition to classical PAH, two distinct phenotypes have emerged: a heart failure with preserved ejection fraction-like phenotype and a lung phenotype. Importantly, the evidence supporting the currently proposed treatment algorithm for PAH has been generated mainly from PAH trials in which patients with cardiopulmonary comorbidities have been underrepresented or excluded. As a consequence, the best therapeutic approach for patients with common PAH with cardiopulmonary comorbidities remains largely unknown and requires further investigation. The present article reviews the relevant literature on the topic and describes the authors' views on the current therapeutic approach for these patients.
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Cardiopatías , Insuficiencia Cardíaca , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/epidemiología , Hipertensión Arterial Pulmonar/terapia , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar Primaria Familiar/complicaciones , Cardiopatías/complicaciones , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapiaRESUMEN
BACKGROUND: Bone morphogenetic proteins 9 and 10 (BMP9 and BMP10), encoded by GDF2 and BMP10, respectively, play a pivotal role in pulmonary vascular regulation. GDF2 variants have been reported in pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). However, the phenotype of GDF2 and BMP10 carriers remains largely unexplored. METHODS: We report the characteristics and outcomes of PAH patients in GDF2 and BMP10 carriers from the French and Dutch pulmonary hypertension registries. A literature review explored the phenotypic spectrum of these patients. RESULTS: 26 PAH patients were identified: 20 harbouring heterozygous GDF2 variants, one homozygous GDF2 variant, four heterozygous BMP10 variants, and one with both GDF2 and BMP10 variants. The prevalence of GDF2 and BMP10 variants was 1.3% and 0.4%, respectively. Median age at PAH diagnosis was 30â years, with a female/male ratio of 1.9. Congenital heart disease (CHD) was present in 15.4% of the patients. At diagnosis, most of the patients (61.5%) were in New York Heart Association Functional Class III or IV with severe haemodynamic compromise (median (range) pulmonary vascular resistance 9.0 (3.3-40.6)â WU). Haemoptysis was reported in four patients; none met the HHT criteria. Two patients carrying BMP10 variants underwent lung transplantation, revealing typical PAH histopathology. The literature analysis showed that 7.6% of GDF2 carriers developed isolated HHT, and identified cardiomyopathy and developmental disorders in BMP10 carriers. CONCLUSIONS: GDF2 and BMP10 pathogenic variants are rare among PAH patients, and occasionally associated with CHD. HHT cases among GDF2 carriers are limited according to the literature. BMP10 full phenotypic ramifications warrant further investigation.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Telangiectasia Hemorrágica Hereditaria , Humanos , Masculino , Femenino , Adulto , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Hipertensión Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Pulmonar Primaria Familiar , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/genética , Fenotipo , Factor 2 de Diferenciación de Crecimiento/genética , Estudios Multicéntricos como AsuntoRESUMEN
The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of randomized controlled trials (RCTs). Thus, we performed a meta-analysis of RCTs that reported outcomes for CTD-PAH. PubMed and EMBASE were searched for CTD-PAH treatment. The selected outcomes were functional class (FC) change, survival rates, 6-min walk distance (6-MWD), clinical worsening (CW), N-terminal prohormone BNP (NT-proBNP), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), and cardiac index (CI). The meta-analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42020153560). Twelve RCTs conducted with 1837 patients were included. The diagnoses were systemic sclerosis in 59%, SLE in 20%, and other CTDs in 21%. The pharmacological interventions were epoprostenol, treprostinil, sildenafil, tadalafil, bosentan, macitentan, ambrisentan, riociguat, and selexipag. There was a significant difference between interventions and placebo in FC, 6MWD, CW, PVR, RAP, and CI that favored intervention. Our analysis showed a 39% reduction in the CW risk with PAH treatment. The short-term survival rates and mean serum NT-proBNP changes were similar between the study and control groups. Treatment for CTD-PAH had favorable effects on clinical and hemodynamic outcomes but not on survival and NT-proBNP levels. Different from the previous meta-analyses that focused on 6-MWD, time to clinical worsening, and CW as outcomes, this meta-analysis additionally reports the pooled analysis of change in FC, hemodynamic measurements (RAP, PVR, CI), and NT-proBNP, some of which have prognostic value for PAH.
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Enfermedades del Tejido Conjuntivo , Hipertensión Arterial Pulmonar , Humanos , Antihipertensivos/uso terapéutico , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/fisiopatología , Fragmentos de Péptidos/sangre , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
This study aimed to investigate the causal role of diabetes mellitus (DM), glycemic traits, and sodium-glucose cotransporter 2 (SGLT2) inhibition in pulmonary arterial hypertension (PAH). Utilizing a two-sample two-step Mendelian randomization (MR) approach, we determined the causal influence of DM and glycemic traits (including insulin resistance, glycated hemoglobin, and fasting insulin and glucose) on the risk of PAH. Moreover, we examined the causal effects of SGLT2 inhibition on the risk of PAH. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Results showed that genetically inferred DM demonstrated a causal correlation with an increased risk of PAH, exhibiting an odds ratio (OR) of 1.432, with a 95% confidence interval (CI) of 1.040-1.973, and a p-value of 0.028. The multivariate MR analysis revealed comparable outcomes after potential confounders (OR = 1.469, 95%CI = 1.021-2.115, p = 0.038). Moreover, genetically predicted SGLT2 inhibition was causally linked to a reduced risk of PAH (OR = 1.681*10-7, 95%CI = 7.059*10-12-0.004, p = 0.002). Therefore, our study identified the suggestively causal effect of DM on the risk of PAH, and SGLT2 inhibition may be a potential therapeutic target in patients with PAH.
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Diabetes Mellitus Tipo 2 , Hipertensión Arterial Pulmonar , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Glucemia , Hipertensión Arterial Pulmonar/complicaciones , Análisis de la Aleatorización Mendeliana , Transportador 2 de Sodio-Glucosa/genética , Transportador 2 de Sodio-Glucosa/uso terapéutico , Hemoglobina Glucada , Polimorfismo de Nucleótido SimpleRESUMEN
Pulmonary hypertension encompasses a range of conditions directly or indirectly leading to elevated pressures within the pulmonary arteries. Five main groups of pulmonary hypertension are recognized, all defined by a mean pulmonary artery pressure of >20 mmHg: pulmonary arterial hypertension (rare), pulmonary hypertension associated with left-sided heart disease (very common), pulmonary hypertension associated with lung disease (common), pulmonary hypertension associated with pulmonary artery obstructions, usually related to thromboembolic disease (rare), and pulmonary hypertension with unclear and/or multifactorial mechanisms (rare). At least 1% of the world's population is affected, with a greater burden more likely in low-income and middle-income countries. Across all its forms, pulmonary hypertension is associated with adverse vascular remodelling with obstruction, stiffening and vasoconstriction of the pulmonary vasculature. Without proactive management this leads to hypertrophy and ultimately failure of the right ventricle, the main cause of death. In older individuals, dyspnoea is the most common symptom. Stepwise investigation precedes definitive diagnosis with right heart catheterization. Medical and surgical treatments are approved for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. There are emerging treatments for other forms of pulmonary hypertension; but current therapy primarily targets the underlying cause. There are still major gaps in basic, clinical and translational knowledge; thus, further research, with a focus on vulnerable populations, is needed to better characterize, detect and effectively treat all forms of pulmonary hypertension.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Anciano , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/etiología , Hipertensión Arterial Pulmonar/complicaciones , Arteria Pulmonar , PulmónRESUMEN
Pulmonary arterial hypertension (PAH) is a complex and fatal cardio-pulmonary vascular disease. Decompensated right ventricular hypertrophy (RVH) caused by cardiomyocyte hypertrophy often leads to fatal heart failure, the leading cause of mortality among patients. Sodium butyrate (SB), a compound known to reduce cardiac hypertrophy, was examined for its potential effect and the underlying mechanism of SB on PAH-RVH. The in vivo study showed that SB alleviated RVH and cardiac dysfunction, as well as improved life span and survival rate in MCT-PAH rats. The in vivo and in vitro experiments showed that SB could attenuate cardiomyocyte hypertrophy by reversing the expressions of H19, let-7g-5p, insulin-like growth factor 1 receptor (IGF1 receptor), and pERK. H19 inhibition restored the level of let-7g-5p and prevented the overexpression of IGF1 receptor and pERK in hypertrophic cardiomyocytes. In addition, dual luciferase assay revealed that H19 demonstrated significant binding with let-7g-5p, acting as its endogenous RNA. Briefly, SB attenuated PAH-RVH by inhibiting the H19 overexpression, restoring the level of let-7g-5p, and hindering IGF1 receptor/ERK activation.
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Hipertensión Pulmonar , MicroARNs , Hipertensión Arterial Pulmonar , Humanos , Ratas , Animales , Hipertrofia Ventricular Derecha , Hipertensión Arterial Pulmonar/complicaciones , Ácido Butírico/farmacología , Ácido Butírico/uso terapéutico , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar Primaria Familiar , MicroARNs/genética , MicroARNs/metabolismo , Factor I del Crecimiento Similar a la InsulinaRESUMEN
OBJECTIVES: End-stage lung disease from primary pulmonary hypertension (PPHTN) and pulmonary venous-occlusive disease (PVOD) may require lung transplantation (LT). While medical therapies exist for the palliation of PPHTN, no therapies exist for PVOD. The study's objective is to compare outcomes of LT in these patients. METHODS: Patients with PPHTN and PVOD who had undergone LT were identified in the UNOS database (2005-2022). Univariable analyses compared differences between groups in demographic, clinical, and post-transplant outcomes. Multivariable logistic regression examined the association between the diagnosis group and survival. Overall survival time between groups was compared using the Kaplan-Meier method. RESULTS: Six hundred and ninety-six PPHTN and 78 PVOD patients underwent LT during the study period. Patients with PVOD had lower pulmonary artery mean pressure (47 vs. 53 mmHg, p < .001), but higher cardiac output (4.51 vs. 4.31 L/min, p = .04). PVOD patients were more likely to receive lungs from donation after cardiac death donors (7.7 vs. 2.9%, p = .04). There were no differences in postoperative complications or length of stay. PVOD was associated with superior survival at 30-day (100 vs. 93%, p = .02) and 90-day post-transplant (93 vs. 83%, p = .03), but not at later time points. In multivariable analyses, PVOD and brain death donor use were associated with better survival up to 90-day mark. CONCLUSIONS: Patients undergoing LT for PVOD had better initial survival, which disappeared after 1 year of transplantation. Donation after circulatory death donor use had a short-term survival disadvantage.
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Hipertensión Pulmonar , Trasplante de Pulmón , Hipertensión Arterial Pulmonar , Enfermedad Veno-Oclusiva Pulmonar , Humanos , Hipertensión Arterial Pulmonar/complicaciones , Enfermedad Veno-Oclusiva Pulmonar/complicaciones , Enfermedad Veno-Oclusiva Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/cirugía , Hipertensión Pulmonar/diagnóstico , PulmónRESUMEN
BACKGROUND: Pulmonary involvement is the leading cause of death in systemic sclerosis (SSc) and may manifest as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), or in combination of both (ILD with pulmonary hypertension [ILD-PH]). The aim of this analysis was to determine prevalence, clinical characteristics, and survival of these different forms within the registry of the German Network for Systemic Sclerosis. RESEARCH QUESTION: Does SSc-associated ILD-PH or ILD without PH affect survival differently, and are there any risk factors that have an additional impact? STUDY DESIGN AND METHODS: Clinical data of 5,831 patients with SSc were collected in the German Network for Systemic Sclerosis registry. Kaplan-Meier estimates were used to compare overall survival in patients with SSc-associated ILD-PH and ILD without PH with patients without pulmonary involvement and those with PAH. The Cox proportional hazard model was used to analyze the influence of pulmonary involvement and other potential predictors on patient survival. RESULTS: Clinical data of 3,257 patients with a mean follow-up time of 3.45 ± 1.63 years have been included in our analysis. At baseline, ILD was present in 34.5%, whereas PH without ILD had a lower prevalence with 4.5%. At the end of follow-up, 47.6% of patients with SSc had ILD, 15.2% had ILD-PH, and 6.5% had PAH. ILD was more frequent in the diffuse cutaneous form (57.3%), whereas PAH did not differ significantly between SSc subtypes. Significant differences in baseline characteristics between PAH vs ILD-PH vs ILD without PH were found for age at diagnosis, sex, SSc subsets, antibody status, FVC, diffusing capacity of the lung for carbon monoxide, and therapy. Overall survival at 5 years was 96.4% for patients without pulmonary involvement and differed significantly between patients with ILD without PH, PAH, and being worst in patients with ILD-PH. Female sex (hazard ratio [HR], 0.3), higher BMI (HR, 0.9), and higher diffusing capacity of the lung for carbon monoxide values (HR, 0.98) were associated with a lower mortality risk. INTERPRETATION: ILD is the most prevalent pulmonary involvement in SSc, whereas the combination of ILD and PH is associated with the most detrimental survival.
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Hipertensión Pulmonar , Enfermedades Pulmonares Intersticiales , Hipertensión Arterial Pulmonar , Esclerodermia Sistémica , Humanos , Femenino , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/tratamiento farmacológico , Estudios de Cohortes , Monóxido de Carbono , Esclerodermia Sistémica/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Hipertensión Pulmonar Primaria Familiar/complicaciones , Hipertensión Arterial Pulmonar/complicacionesRESUMEN
OBJECTIVE: Regular clinical assessment for complications of systemic sclerosis (SSc) such as pulmonary arterial hypertension (PAH) is essential for early institution of therapy and improved outcomes. The objective of this study was to determine the impact of COVID-19 pandemic-related restrictions on health care access of patients with SSc, including screening for PAH. METHODS: South Australian and Victorian patients enrolled in the Australian Scleroderma Cohort Study were surveyed about their perceptions of the impact of the pandemic on mental well-being, access to medications, investigations, and management of SSc. Frequency of annual rheumatology assessments, pulmonary function tests (PFT), and transthoracic echocardiography (TTE) to screen for PAH were compared with rates from before the pandemic. RESULTS: A total of 312 of 810 patients with SSc responded (38.5% response); 273 were female (87.5%), the median age was 64.7 years, 77.2% had limited disease, the median illness duration was 15.6 years, 15.7% were immunosuppressed, 32.1% had interstitial lung disease, and 6.4% had PAH. A total of 65.7% of consultations were by telehealth, of which 81.2% were by telephone. Compared with respondents in South Australia (n = 109), Victorian respondents (n = 203) experiencing prolonged lockdown, reported reduced access to their rheumatologist (49.3% vs 27.9%; P = 0.004), greater use of consultation by video (17.3% vs 2.1%; P = 0.008), greater health care disruption (49.0% vs 23.2%; P < 0.001), and worse mental health (P = 0.002). Respondents reported reduced access to PFT and TTE (31.7% and 22.5%, respectively). Annual visits, PFT, TTE, and new diagnoses of PAH were reduced in 2020 to 2022 compared with 2011 to 2019. CONCLUSION: The COVID-19 pandemic-related disruption to health care for patients with SSc was associated with worse mental health and reduced screening and diagnosis of PAH, which may impact long-term outcomes.
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COVID-19 , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Esclerodermia Sistémica , Humanos , Femenino , Persona de Mediana Edad , Masculino , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/epidemiología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Pulmonar/etiología , Pandemias , Estudios de Cohortes , Australia/epidemiología , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/epidemiología , Accesibilidad a los Servicios de Salud , Prueba de COVID-19RESUMEN
OBJECTIVES: Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH. METHODS: We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes. RESULTS: This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34) they were 97%, 77% and 61%; for MCTD-PAH (n = 33) they were 97%, 70% and 59%; for UCTD-PAH (n = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P = 0.001). In these patients, the survival estimates were significantly better with initial ERA-PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P = 0.016 and P = 0.012, respectively). CONCLUSIONS: Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA-PDE5i combination therapy compared with initial monotherapy.
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Enfermedades del Tejido Conjuntivo , Hipertensión Pulmonar , Lupus Eritematoso Sistémico , Enfermedad Mixta del Tejido Conjuntivo , Hipertensión Arterial Pulmonar , Esclerodermia Sistémica , Humanos , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/complicaciones , Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Enfermedad Mixta del Tejido Conjuntivo/tratamiento farmacológico , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Enfermedades del Tejido Conjuntivo/diagnóstico , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar Primaria Familiar/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Esclerodermia Sistémica/complicacionesRESUMEN
Autoimmune diseases can express pathologies in specific organs (e.g. thyroid, pancreas, skin) or generate systemic pathologies (generalized lupus erythematosus, rheumatoid arthritis, systemic sclerosis), the latter usually present systemic inflammatory phenomena. Some studies have reported alterations in right ventricular contractility in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and juvenile idiopathic arthritis, which may contribute to the known outcome of increased cardiovascular risk. However, there is not much information available on the causes that generate these alterations, the most likely being small vessel damage and fibrosis due to subclinical inflammation.1-5 In this sense, the disease in which the alterations of the right ventricle have been more studied is systemic sclerosis, specifically at the changes induced due to pulmonary arterial hypertension, this being one of the main causes of death in this group of patients after the significant decrease in mortality associated with the sclerodermic renal crisis with the treatment of angiotensin-converting enzyme inhibitors. In this review, we will focus on explaining the structural and functional changes that occur in the right ventricle of patients with systemic sclerosis, from early alterations to late complications. In this context, it is necessary to distinguish between right heart alterations that occur in patients with systemic sclerosis and pulmonary arterial hypertension and those that occur without pulmonary arterial hypertension and that can be attributed to other causes such as microvascular damage or myocardial fibrosis.