Treatment patterns and factors associated with adherence in pulmonary arterial hypertension.

OBJECTIVE: Improving understanding of actual pulmonary hypertension (PH) treatment adherence patterns is crucial to properly treating these patients. We aimed to primarily assess adherence to treatments used for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) specific therapies, identify potential factors related to it and secondly describe its treatment patterns. METHODS: A 6-month observational cross-sectional study in a tertiary care hospital was conducted. Patients with PH-targeted therapy who picked it up in the ambulatory hospital pharmacy and who had been on treatment with the same drug for at least 1 year were included. Adherence was assessed as: 1) Proportion of days covered (PDC); and 2) Simplified Medication Adherence Questionnaire (SMAQ). PDC ≥80% was considered adherent. Statistical analyses were performed to evaluate the study outcomes. Logistic regressions were estimated to identify the association between baseline characteristics and factors associated with adherence. P < 0.05 indicated statistical significance. RESULTS: A total of 63 patients with 127 different treatments were included, 71.4% were females with a mean age (SD) of 59 (15) years. PAH was the most common diagnosis (74.6%). Double therapy was used in 39.7% of patients, being the combination of Macitentan + Tadalafil and Ambrisentan + Tadalafil the most prescribed. Endothelin receptor antagonists were the most used treatment (40.2%). Adherence according to PDC was 93.7%, showing no great differences depending on the targeted drug used, and according to SMAQ 61.9%. The agreement degree of both methods was slight (65.1%; Kappa 0.12). Only female sex (OR: 0.23, 95% CI: 0.06-0.90; p = 0.035) was associated with worse adherence in the SMAQ method but not in the PDC. Adverse events were reported by a 55.6% of participants and the perception of effective treatment was high (95.2%). CONCLUSIONS: Adherence to PH therapy differs depending on the assessment method; PDC showed greater adherence rate than SMAQ. According to SMAQ, female sex may have a negative impact on adherence in this cohort, but PDC revealed no factors influencing it. No notable differences in adherence between treatment types were found and generally patients felt the treatments were effective in controlling their disease.

Fisiopatología de la hernia diafragmática congénita en el recién nacido / Pathophysiology of congenital diaphramatic hernia in the newborn

La hernia diafragmática congénita es una discontinuidad del diafragma con herniación de los órganos abdominales a la cavidad torácica, actualmente se postula una hipótesis dual para su origen. Su fisiopatología está determinada por la hipoplasia pulmonar, la hipertensión pulmonar y la disfunción ventricular, entender estos elementos es necesario para un adecuado manejo y la mejoría del pronóstico.

Congenital diaphragmatic hernia is a discontinuity of the diaphragm with herniation of the abdominal organs into the thoracic cavity, currently a dual hypothesis for its origin is postulated. Its pathophysiology is determined by pulmonary hypoplasia, pulmonary hypertension and ventricular dysfunction, understanding these elements is necessary for adequate management and improve prognosis.

Cierre de conducto arterioso persistente con dispositivo OcclutechTM, experiencia en un país andino / Closure of patent ductus arteriosus with OcclutechTM device, experience in an andean country

Resumen Objetivo: Presentar la experiencia en un país andino con el dispositivo OcclutechTM Duct Occluder para el cierre del conducto arterioso persistente. Método: Estudio observacional, retrospectivo, de corte transversal con análisis estadístico básico. Periodo: diciembre/2014 a diciembre/2022. Datos: historia clínica, informes de laboratorio de cateterismo. Resultados: Cuarenta y seis pacientes; de sexo femenino 71.3%, de sexo masculino 28.7%; edad: 0.6-38 años (mediana [Me]: 5.2); peso: 6.3-60 kg (Me: 16.5). Procedencia: andina 91.3%, costa 8.7%. Tipos de conducto arterioso persistente: E 54.4%, A 32.6%, D 13%. Diámetro ductal mínimo: 1.8-11.8 mm (Me: 3.5). Presión media de la arteria pulmonar previo a la oclusión: 14-67 mmHg (Me: 27). Índice de resistencias vasculares pulmonares previo a la oclusión: 0.28-4.9 UW/m2 (Me: 1.3). Fueron catalogados como conductos arteriosos persistentes hipertensivos seis de ellos. Tasa de oclusión: inmediata el 47.8%, a las 24 horas el 81%, a los seis meses el 100%. Tiempo de fluoroscopia: 2-13.8 minutos (Me: 4). Complicaciones: un dispositivo migrado. Seguimiento: 1-6.5 años. Conclusiones: El dispositivo OcclutechTM Duct Occluder fue efectivo y seguro para el cierre de conducto arterioso persistente tipo E, A y D en habitantes de baja y alta altitud, ya sea que estos hubieran sido niños o adultos, incluso cuando estos conductos arteriosos fueron hipertensivos.

Abstract Objective: To communicate the experience in an Andean country with the OcclutechTM Duct Occluder device for the closure of patent ductus arteriosus. Method: Observational, retrospective, cross-sectional study with basic statistical analysis. Period: December/2014 to December/2022. Data: medical chart, reports of catheterization. Results: Forty-six patients, female 71.3%, male 28.7%; age: 0.6-38 years-old (median [Me]: 5.2); weight: 6.3-60 kg (Me: 16.5). Origin: andean 91.3%, coast 8.7%. Types of patent ductus arteriosus: E 54.4%, A 32.6%, D 13%. Minimum ductal diameter: 1.8-11.8 mm (Me: 3.5). Mean pulmonary artery pressure prior to occlusion: 14-67 mmHg (Me: 27). Pulmonary vascular resistance index prior to occlusion: 0.28-4.9 WU/m2 (Me: 1.3). Six of them were classified as hypertensive patent ductus arteriosus. Occlusion rate: 47.8% immediate, 81% at 24 hours, 100% after six months. Fluoroscopy time: 2-13.8 minutes (Me: 4). Complications: a migrated device. Follow-up: 1-6.5 years. Conclusions: OcclutechTM Duct Occluder device was effective and safe for the closure of patent ductus arteriosus type E, A and D in low-altitude and high-altitude dwellers, whether they were children or adults, even when these ductus arteriosus were hypertensive.

Cardiopulmonary phenotype in systemic sclerosis associated pulmonary hypertension.

INTRODUCTION: Pulmonary hypertension (PH) associated with systemic sclerosis (SSc) increases morbidity and mortality. Cardiopulmonary comorbidities, as per the 2021 PH consensus, play a role in the choice of therapy between monotherapy and combination therapy. METHODS: A cross-sectional study was conducted in patients with SSc based on the 2013 ACR/EULAR criteria or very early disease (VEDOSS 2011). PH was considered if they met the following criteria: pulmonary artery systolic pressure (PASP)>39mmHg or peak tricuspid regurgitation velocity (PTRV)>3.4m/s, PASP between 33 and 39mmHg or PTRV between 2.9 and 3.4m/s plus two additional findings suggestive of PH. PH was classified as type 2 if LVEF<50% or moderate to severe diastolic dysfunction was present; type 3 if extensive interstitial disease on tomography>20% or forced vital capacity (FVC)<75%; type 4 if abnormalities related to embolism were detected on scintigraphy or tomography. If patients did not meet these criteria, they were classified as type 1 PH. Complete data on cardiopulmonary risk factors and other factors were required. The frequency of these factors in the population and differences between groups based on risk factors were estimated. RESULTS: A total of 228 patients were selected. Three had type 2 PH, 24 had type 3, and 40 had type 1 PH, with the majority (75%) having at least one cardiopulmonary risk factor, and 47.5% having more than one. Mild diastolic dysfunction (25%) and hypertension (35%) were the most prevalent. In the type 1 PH group, those with risk factors experienced an increase in the number of years with Raynaud's phenomenon, anticentromere antibodies, and gastrointestinal symptoms (p<0.05). CONCLUSION: In patients with PH, 75% have one, and 45% have two or more risk factors.

Chronic thromboembolic pulmonary hypertension treatment and sex: Systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart failure and death. While pulmonary endarterectomy is the treatment of choice, some patients might benefit from medical therapy or balloon pulmonary angioplasty. Sex differences in outcomes of these therapies are not well characterized. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis to investigate sex differences in outcomes of various therapies for CTEPH. We searched MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library databases between January 1, 2010 and April 30, 2021, published in English. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I2 statistic. We assessed publication bias using Begg's and Egger's tests. This study is registered in PROSPERO, CRD42021268504. RESULTS: A total of 19 studies met the eligibility criteria, but only 3 trials provided separate outcomes for women and men. Two studies evaluated the efficacy of BPA, and one study evaluated the efficacy of riociguat (129 patients). Overall, 57.3% of patients were women and 62.6% were in functional class III. Mean time of follow-up was 55.5 (SD 26.1) weeks. Women showed a significantly better response in cardiac index (mean difference [MD], 0.10L/min/m2; 95% confidence interval [CI], 0.04-0.16; I2=0%; P=0.001). Alternatively, the reduction of pulmonary vascular resistances was significantly higher for men than for women (MD, 161.17dynscm-5; 95% CI, 67.99-254.35; I2=0%; P=0.0007). CONCLUSIONS: Women and men might show different hemodynamic responses to riociguat or BPA for CTEPH.

[The role of nursing in right heart catheterization. Advantages from peripheral venous access]. / Papel de enfermería en el cateterismo cardiaco derecho. Ventajas del acceso venoso periférico.

INTRODUCTION: Pulmonary hypertension (PH) is a serious disease that requires early diagnosis to achieve a better patient prognosis. Right heart catheterization (RHC) has become the main diagnostic test for this disease, measuring the pressures from the right heart chambers invasively, using a catheter placed through venous access. Nursing performance has an important role in RHC through peripheral venous access due to its well-done skills for canalization and knowledge about the management and care of these accesses. RHC performed through peripheral venous access provide advantages over those performed through central venous access. OBJECTIVE: To analyze the benefits from RHC through peripheral venous access compared to those performed through central venous access, as well as highlighting the role of nursing during this type of procedures. METHOD: A retrospective, descriptive, and observational study was performed for patients who underwent RHC in our center between January 2019 to January 2023. We analyzed clinical characteristics, access, fluoroscopy parameters, periprocedural complications, and hospital admissions. RESULT: A total of 115 patients were included. The average age was 65±12 years, with 58.1% of females. Risk stratification of PH was the reason for conducting RHC in 82.9%. The anterocubital veins became the main approach (72.2%), performed by hemodynamics nurses, while the central venous ones composed the rest (27.8%), which were done by cardiology specialized doctors. We observed a significant reduction in radiation dose in RHC via anterocubital route compared to central venous access (4.4Gycm2 vs 12.5Gycm2 [IQR: 4.5]; P<.001), and it does also in fluoroscopy times (2.3minutes vs 4.6minutes [IQR: 2.6]; P<.001). No complications were recorded, independently of the approach. Patients who underwent a scheduled catheterization were discharged more frequently on the same day of the procedure whether a peripheral approach was performed (77.2%, 44 of 57 patients), in comparison with the central one (28.6%) (P=.001). CONCLUSIONS: The RHC is an essential tool for the diagnosis of PH, achieving nursing such an important role for those performed by peripheral venous access. Peripheral venous access provides benefits and advantages like the reduction of radiation exposure and scan times, reduced hospital stay. All this could bring greater comfort, safety and better quality of care to the patient.

Hipertensión pulmonar y leiomiomas uterinos, ¿existe relación causal? Serie de casos y revisión fisiopatológica / Pulmonary Hypertension and Uterine Leiomyomas, Is there a Causal Relationship? Case Series and Pathophysiological Review

Introducción: Los leiomiomas uterinos son un tipo de neoplasia benigna de frecuente aparición en mujeres de edad reproductiva, relacionados con enfermedad tromboem- bólica venosa. Este vínculo surge del efecto producido por la compresión de fibromas que genera estasis venosa en la región pelviana. Sin embargo, este pareciera no ser el único factor que lo relaciona con el desarrollo posterior de hipertensión pulmonar, sino que su presencia es gatillo de una serie de fenómenos que influyen sobre la vasculatu - ra pulmonar y también a nivel sistémico. Método: Revisión de una serie de casos (seis) atendidos en nuestra unidad, seguido de una revisión sobre la relación entre leiomio- mas y distintas formas de hipertensión pulmonar con una revisión desde la fisiopatología. Resultado y conclusiones: Encontramos sustento bibliográfico en los múltiples caminos fisiopatológicos que relacionan los mediadores vasculares comunes, que parecieran ser el punto clave en la relación entre estas dos patologías.

Introduction: Uterine leiomyomas are a type of benign neoplasm that frequently appears in women of reproductive age, related to venous thromboembolic disease. This link arises from the effect produced by the compression of fibroids, which generates venous stasis in the pelvic region. However, this seems not to be the only factor that re- lates it to the subsequent development of pulmonary hypertension, but rather its presence is a trigger for a series of phenomena that influence the pulmonary vasculature and also at a systemic level. Method: Review of a series of cases (six) cared for in our unit, followed by a review on the relationship between leiomyomas and different forms of pulmonary hypertension with a review from the pathophysiology. Result and conclusions: We found bibliographic support in the multiple pathophysiological paths that relate the common vascular mediators, which appear to be the key point in the relationship between these two pathologies.

[The importance of data in Pulmonary Arterial Hypertension: from international registries to Machine Learning]. / La importancia de los datos en la hipertensión arterial pulmonar: de los registros internacionales al machine learning.

Real-world registries have been critical to building the scientific knowledge of rare diseases, including Pulmonary Arterial Hypertension (PAH). In the past 4 decades, a considerable number of registries on this condition have allowed to improve the pathology and its subgroups definition, to advance in the understanding of its pathophysiology, to elaborate prognostic scales and to check the transferability of the results from clinical trials to clinical practice. However, in a moment where a huge amount of data from multiple sources is available, they are not always taken into account by the registries. For that reason, Machine Learning (ML) offer a unique opportunity to manage all these data and, finally, to obtain tools that may help to get an earlier diagnose, to help to deduce the prognosis and, in the end, to advance in Personalized Medicine. Thus, we present a narrative revision with the aims of, in one hand, summing up the aspects in which data extraction is important in rare diseases -focusing on the knowledge gained from PAH real-world registries- and, on the other hand, describing some of the achievements and the potential use of the ML techniques on PAH.

Value of exercise right heart catheterization in the differential diagnosis of chronic thromboembolic pulmonary disease.

INTRODUCTION AND OBJECTIVES: Chronic thromboembolic disease refers to the presence of chronic thrombotic pulmonary vascular thrombosis without pulmonary hypertension (PH) at rest but with exercise limitation after pulmonary embolism (PE). Our aim was to evaluate the hemodynamic response to exercise in these patients and its correlation with the values reached in cardiopulmonary exercise testing. METHODS: We included symptomatic patients with persistent pulmonary thrombosis after PE. We excluded patients with left heart disease or significant PH (mean pulmonary arterial pressure [mPAP] >25mmHg, pulmonary vascular resistance >3 WU, and pulmonary capillary wedge pressure [PCWP] >15mmHg). Cardiopulmonary exercise testing and exercise right heart catheterization were performed. Exercise-induced precapillary PH was defined as mPAP/CO slope >3 and PCWP/CO slope <2mmHg/l/min. The hemodynamic response and the values obtained in cardiopulmonary exercise testing were compared between patients with and without exercise-induced precapillary PH. RESULTS: We studied 36 patients; 4 were excluded due to incomplete hemodynamic data. Out of the 32 patients analyzed; 3 developed a pathological increase in PCWP. Among the remaining 29 patients (mean age, 49.4±13.7 years, 34.5% women), 13 showed exercise-induced PH. Resting mPAP was higher in those who developed exercise-induced PH (23.3±5.4 vs 19.0±3.8mmHg; P=.012), although CO was similar in the 2 groups. Patients with exercise-induced PH exhibited data of ventilatory inefficiency with reduced values of end-tidal CO2 pressure at the anaerobic threshold (32.8±3.0 vs 36.2±3.3mmHg; P=.021) and a higher Ve/VCO2 slope (34.2±4.8 vs 30.7±5.0; P=.049). CONCLUSIONS: Exercise limitation and ventilatory inefficiency could be attributable to exercise-induced precapillary PH in a subgroup of patients with persistent pulmonary thrombosis and dyspnea.

[Update in the management of chronic thrombo-embolic pulmonary hypertension]. / Actualización del abordaje de la hipertensión pulmonar tromboembólica crónica.

Chronic thrombo-embolic pulmonary hypertension (CTEPH) is a potentially curable form of pulmonary hypertension (PH) that develops in up to 3% of patients after pulmonary embolism (PE). In these patients, PE does not resolve, leading to organized fibrotic clots, with the development of precapillary PH as a result of the proximal obstruction of the pulmonary arteries. In addition, a distal microvasculopathy may also develop, contributing to the increase of pulmonary vascular resistance. Transthoracic echocardiography is the diagnostic tool that allows to establish the suspicion of PH. Ventilation-perfusion lung scintigraphy is the fundamental tool in the study of patients with suspected CTEPH; if it is normal, virtually rules out the diagnosis. Right heart catheterization is mandatory for the diagnosis of these patients. CTEPH is defined as the existence of symptoms, residual perfusion defects and precapillary PH after a minimum period of three months of anticoagulation. Pulmonary angiography helps determine the extent and surgical accessibility of thromboembolic lesions. CTEPH patients are candidates for long-term anticoagulation. Pulmonary endarterectomy is the treatment of choice, resulting in significant clinical and hemodynamic improvement. About 25% of patients have residual PH post-endarterectomy. Balloon pulmonary angioplasty is an endovascular technique that targets more distal lesions, being potentially useful for patients with inoperable CTEPH or persistent/recurrent PH post-endarterectomy. Both types of patients may also benefit from pharmacological treatment for PH. These three therapies are the cornerstone of CTEPH treatment, which has evolved towards a multimodal approach.

Tromboendarterectomía pulmonar en hipertensión pulmonar tromboembólica crónica. Experiencia binacional Uruguay-Argentina / Pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension. Binational experience Uruguay-Argentina / Tromboendarterectomia pulmonar na hipertensão pulmonar tromboembólica crônica. Experiência binacional Uruguai-Argentina

Introducción: La tromboendarterectomía pulmonar (TEA) es la principal herramienta terapéutica en hipertensión pulmonar tromboembólica crónica (HPTEC), potencialmente curativa. Se analiza la experiencia de 13 años de TEAs de pacientes uruguayos en el marco del convenio con el Hospital Universitario Fundación Favaloro (HUFF-Argentina). Metodología: Estudio analítico, observacional y retrospectivo de todas las TEAs realizadas entre 2011 y 2023. Resultados: Se realizaron 15 TEAs. 46 ± 17 años, 67% hombres. Diez pacientes tenían antecedentes de enfermedad tromboembólica previa y 8 hipercoagulabilidad. El tiempo desde el inicio de los síntomas al diagnóstico fue de 36 (22-78) meses. Ochenta por ciento se encontraba en CF III, con una distancia total recorrida en la prueba de la marcha de 6 minutos de 375 (272-458) metros, severidad ecocardiográfica (TAPSE/PAPs 0,22 ± 0,08 mm/mmHg) y hemodinámica (RVP 11 ± 5 UW) que mejoraron significativamente en el posoperatorio temprano. La mortalidad intrahospitalaria fue del 20% que se mantuvo en el seguimiento de 34 (7-97) meses excepto un paciente que murió por una nueva embolia de pulmón a los 3 años. Todos los fallecidos tenían una hemodinamia preoperatoria significativamente más grave (RVP 19 ± 6 UW, índice cardíaco 1,5 ± 0,4 L/min/m2). Seis sobrevivientes (50%) presentaron HP residual asociada a una mayor PAPm y RVP preoperatorias y menor recuperación funcional y ecocardiográfica a corto plazo (P <0,05), dos de los cuales recibieron terapia específica posterior al procedimiento. Conclusiones: La TEA determinó mejoría clínica, ecocardiográfica y hemodinámica. Seis supervivientes (50%) normalizaron la hemodinamia de reposo. La severidad hemodinámica preoperatoria dado por las lesiones obstructivas y microangiopatía distales se asoció con una alta tasa de complicaciones y mortalidad perioperatorias. La reducción del retardo en el diagnóstico y tratamiento junto con una mayor tasa de TEAs/año podrían reducir las complicaciones y mejorar el pronóstico.

Summary Introduction: Pulmonary thromboendarterectomy (PTE) is the main therapeutic tool for chronic thromboembolic pulmonary hypertension (CTEPH), and is potentially curative. The experience of 13 years of PTEs on Uruguayan patients under the agreement with the University Hospital Fundación Favaloro (HUFF-Argentina) is analyzed. Methodology: Analytical, observational, and retrospective study of all PTEs performed between 2011 and 2023. Results: Fifteen PTEs were performed. Age was 46 ± 17 years, 67% male. Ten patients had a history of prior thromboembolic disease, and 8 had hypercoagulability. The time from symptom onset to diagnosis was 36 (22-78) months. Eighty percent were in NYHA Functional Class III, with a total distance walked in the 6-minute walk test of 375 (272-458) meters, echocardiographic severity (TAPSE/sPAP 0,22 ± 0,08 mm/mmHg), and hemodynamic severity (PVR 11 ± 5 WU) which significantly improved in the early postoperative period. In-hospital mortality was 20% and remained at a follow-up of 34 (7-97) months, except for one patient who died from a new pulmonary embolism at 3 years. All deceased patients had significantly more severe preoperative hemodynamics (PVR 19 ± 6 WU, cardiac index 1,5 ± 0,4 L/min/m²). Six survivors (50%) presented with residual PH associated with higher preoperative mPAP and PVR and lower short-term functional and echocardiographic recovery (P <0,05), two of whom received specific therapy post-procedure. Conclusions: PTE resulted in clinical, echocardiographic, and hemodynamic improvement. Six survivors (50%) normalized resting hemodynamics. Preoperative hemodynamic severity due to distal obstructive lesions and microangiopathy was associated with a high rate of perioperative complications and mortality. Reducing the delay in diagnosis and treatment and a higher rate of PTEs/year could reduce complications and improve prognosis.

Introdução: A tromboendarterectomia pulmonar (TEP) é a principal ferramenta terapêutica na hipertensão pulmonar tromboembólica crônica (HPTEC), potencialmente curativa. Analisa-se a experiência de 13 anos de TEPs em pacientes uruguaios no âmbito do convênio com o Hospital Universitário Fundação Favaloro (HUFF-Argentina). Metodologia: Estudo analítico, observacional e retrospectivo de todas as TEPs realizadas entre 2011 e 2023. Resultados: Foram realizadas 15 TEPs. Idade de 46 ± 17 anos, 67% homens. Dez pacientes tinham antecedentes de doença tromboembólica prévia e 8 hipercoagulabilidade. O tempo desde o início dos sintomas até o diagnóstico foi de 36 (22-78) meses. Oitenta por cento encontravam-se em Classe Funcional III, com uma distância total percorrida no teste de caminhada de 6 minutos de 375 (272-458) metros, gravidade ecocardiográfica (TAPSE/sPAP 0,22 ± 0,08 mm/mmHg) e hemodinâmica (RVP 11 ± 5 UW) que melhoraram significativamente no pós-operatório precoce. A mortalidade intra-hospitalar foi de 20% e manteve-se no seguimento de 34 (7-97) meses, exceto um paciente que faleceu por uma nova embolia pulmonar aos 3 anos. Todos os falecidos apresentavam hemodinâmica pré-operatória significativamente mais grave (RVP 19 ± 6 UW, índice cardíaco 1,5 ± 0,4 L/min/m²). Seis sobreviventes (50%) apresentaram HP residual associada a maior PAPm e RVP pré-operatórias e menor recuperação funcional e ecocardiográfica a curto prazo (P <0,05), dois dos quais receberam terapia específica pós-procedimento. Conclusões: A TEP resultou em melhora clínica, ecocardiográfica e hemodinâmica. Seis sobreviventes (50%) normalizaram a hemodinâmica de repouso. A gravidade hemodinâmica pré-operatória devido a lesões obstrutivas e microangiopatia distal foi associada a uma alta taxa de complicações e mortalidade perioperatória. A redução do atraso no diagnóstico e tratamento juntamente com uma maior taxa de TEPs/ano poderia reduzir as complicações e melhorar o prognóstico.

External validation of the InShape II study algorithm for exclusion of chronic thromboembolic pulmonary hypertension in patients with pulmonary thromboembolism.

BACKGROUND AND AIM: The most severe long-term complication of pulmonary embolism (PE) is chronic thromboembolic pulmonary hypertension (CTEPH), and its early diagnosis often requires numerous diagnostic tests. The InShape II study proposes an early screening algorithm that aims to reduce the number of echocardiographic studies. The objective of our study is to validate this algorithm in our patient cohort. MATERIALS AND METHODS: We retrospectively analyzed patients admitted to Hospital Rey Juan Carlos between November 2017 and February 2020, who were diagnosed with PE based on computed tomography angiography (CTA). Patients were followed for at least one year, and clinical, laboratory, and complementary test data were collected at three months and one year. The InShape II algorithm was applied to these patients to validate its results. RESULTS: During the study period, 236 patients were diagnosed with PE, of which 137 were excluded. The algorithm was validated in 99 patients. Applying the InShape II score, 19 echocardiograms would have been performed (three of them with intermediate-high probability of CTEPH), while 80 echocardiograms would have been avoided (two of them with intermediate-high probability). This yielded a sensitivity of 60% and a specificity of 83% for the score, with an area under the curve (AUC) of 0.715 (95% CI: 0.472-0.958). CONCLUSIONS: Our results support the notion that the InShape II algorithm could be a useful tool for initial screening of CTEPH in low-incidence settings, as it would avoid unnecessary echocardiograms that do not provide additional value.

Análisis ecocardiográfico de la variabilidad de la presión sistólica arterial pulmonar en la hipertensión pulmonar / Echocardiographic analysis of pulmonary arterial systolic pressure in pulmonary hypertension

Resumen Introducción: La confiabilidad de la presión sistólica arterial pulmonar por ecocardiografía transtorácica se encuentra limitada por su variabilidad para definir la hipertensión pulmonar. Objetivo: Conocer la variabilidad en la presión sistólica arterial pulmonar estimada por ecocardiografía en la hipertensión pulmonar. Métodos: En el periodo 2016-2020 se captaron sujetos con hipertensión pulmonar que tuvieron estimada la presión sistólica de la arteria pulmonar por ecocardiografía transtorácica y por cateterismo cardiaco derecho. Se obtuvieron sus variables demográficas. Los datos se analizaron con el estadístico descriptivo de Bland-Altman y el coeficiente de correlación intraclase (intervalo de confianza al 95%). Resultados: Se estudiaron 152 sujetos, edad 60 ± 12 años. Índice de masa corporal 27.64 ± 4.69 kg/m2. La presión sistólica de la arteria pulmonar por ecocardiografía transtorácica 58.99 ± 18.62 vs. cateterismo cardiaco 55.43 ± 16.79. Diferencia media (sesgo) -3.6 (29.1, -36.2) y coeficiente de correlación intraclase 0.717 (0.610, 0.794). Conclusiones: La variabilidad es amplia y el acuerdo es sustancial con la presión sistólica de la arteria pulmonar. Se aconseja estimarla solo como tamizaje de la hipertensión pulmonar.

Abstract Introduction: The reliability of pulmonary arterial systolic pressure by transthoracic echocardiography is limited by its variability to define pulmonary hypertension. Objective: To know the variability of pulmonary arterial systolic pressure estimated by echocardiography in pulmonary hypertension. Their demographic variables were obtained. Methods: From 2016-2020 subjects with pulmonary hypertension were recruited, with pulmonary artery systolic pressure estimated by transthoracic echocardiography and by right heart catheterization. Data were analyzed using the Bland-Altman descriptive statistic and the intraclass correlation coefficient (95% confidence interval). Results: 152 subjects, age 60 ± 12 years, were studied. Body mass index 27.64 ± 4.69 kg/m2. The pulmonary artery systolic pressure estimated by transthoracic echocardiography 58.99 ± 18.62 vs. cardiac catheterization 55.43 ± 16.79 mmHg. Mean difference (bias) -3.6 (29.1, -36.2) and intraclass correlation coefficient 0.717 (0.610, 0.794). Conclusions: Variability is wide, and agreement is substantial for pulmonary artery systolic pressure. It is recommended to estimate only as screening for pulmonary hypertension.

Echocardiographic analysis of pulmonary arterial systolic pressure in pulmonary hypertension.

INTRODUCTION: The reliability of pulmonary arterial systolic pressure by transthoracic echocardiography is limited by its variability to define pulmonary hypertension. OBJECTIVE: To know the variability of pulmonary arterial systolic pressure estimated by echocardiography in pulmonary hypertension. Their demographic variables were obtained. METHODS: From 2016-2020 subjects with pulmonary hypertension were recruited, with pulmonary artery systolic pressure estimated by transthoracic echocardiography and by right heart catheterization. Data were analyzed using the Bland-Altman descriptive statistic and the intraclass correlation coefficient (95% confidence interval). RESULTS: 152 subjects, age 60 ± 12 years, were studied. Body mass index 27.64 ± 4.69 kg/m2. The pulmonary artery systolic pressure estimated by transthoracic echocardiography 58.99 ± 18.62 vs. cardiac catheterization 55.43 ± 16.79 mmHg. Mean difference (bias) -3.6 (29.1, -36.2) and intraclass correlation coefficient 0.717 (0.610, 0.794). CONCLUSIONS: Variability is wide, and agreement is substantial for pulmonary artery systolic pressure. It is recommended to estimate only as screening for pulmonary hypertension.

INTRODUCCIÓN: La confiabilidad de la presión sistólica arterial pulmonar por ecocardiografía transtorácica se encuentra limitada por su variabilidad para definir la hipertensión pulmonar. OBJETIVO: Conocer la variabilidad en la presión sistólica arterial pulmonar estimada por ecocardiografía en la hipertensión pulmonar. MÉTODOS: En el periodo 2016-2020 se captaron sujetos con hipertensión pulmonar que tuvieron estimada la presión sistólica de la arteria pulmonar por ecocardiografía transtorácica y por cateterismo cardiaco derecho. Se obtuvieron sus variables demográficas. Los datos se analizaron con el estadístico descriptivo de Bland-Altman y el coeficiente de correlación intraclase (intervalo de confianza al 95%). RESULTADOS: Se estudiaron 152 sujetos, edad 60 ± 12 años. Índice de masa corporal 27.64 ± 4.69 kg/m2. La presión sistólica de la arteria pulmonar por ecocardiografía transtorácica 58.99 ± 18.62 vs. cateterismo cardiaco 55.43 ± 16.79. Diferencia media (sesgo) ­3.6 (29.1, ­36.2) y coeficiente de correlación intraclase 0.717 (0.610, 0.794). CONCLUSIONES: La variabilidad es amplia y el acuerdo es sustancial con la presión sistólica de la arteria pulmonar. Se aconseja estimarla solo como tamizaje de la hipertensión pulmonar.

Pulmonary artery obstruction index, pulmonary artery diameter and right ventricle strain as prognostic CT findings in patient with acute pulmonary embolism.

OBJECTIVE: This study was designed to determine predictors of pulmonary hypertension and signs of right heart dysfunction caused by pulmonary embolism (PE) that may lead to early detection of high-risk patients. So the predictive value of pulmonary artery obstruction index (PAOI), measured by pulmonary CT angiography (PCTA) in the acute setting, in predicting the patients susceptible to PE cardiac complications was evaluated. Also two other PCTA indices, pulmonary artery diameter (PAD), and right ventricle (RV) strain, in these patients were investigated and their predictive value for cardiac complications on follow up echocardiography were demonstrated. MATERIALS AND METHODS: In the study 120 patients with a definite diagnosis of PE were included. The PAOI, PAD and RV strain were measured using PCTA at the time of the initial diagnosis. Transthoracic echocardiography was done 6 months after the diagnosis of PE and RV echocardiographic indices were measured. Pearson correlation was used to investigate correlation between PAOI, PAD, RV strain and signs of right heart dysfunction. RESULTS: PAOI was strongly correlated with systolic pulmonary artery pressure (SPAP) (r=0.83), RV systolic pressure (r=0.78) and RV wall thickness (r=0.61) in long-term follow up echocardiography. A higher rate of RV dysfunction and RV dilation was detected among the patients with higher PAOI (P<0.001). PAOI≥18 was strongly predictive for development of RV dysfunction. Also developments of pulmonary hypertension, RV systolic hypertension, RV dilation, RV dysfunction, and RV hypertrophy were significantly more common among patients with higher PAD and RV strain (P<0.001). CONCLUSIONS: PAOI, PAD and RV strain are sensitive and specific PCTA indices that can predict the development of long-term complications such as pulmonary hypertension and right heart dysfunction, at the time of initial PE diagnosis.

La prueba cardiopulmonar de ejercicio contribuye a determinar con precisión el riesgo en pacientes con hipertensión pulmonar de bajo riesgo / Cardiopulmonary Exercise Testing Contributes to Accurate Risk Assessment in Patients with Low-risk Pulmonary Hypertension

RESUMEN Introducción : Las guías europeas de hipertensión arterial pulmonar (HAP) estratifican el riesgo valiéndose de características clínicas y estudios complementarios entre los cuales está la prueba cardiopulmonar de ejercicio (PCPE), de la cual toma en cuenta 3 parámetros: el consumo de O2 (VO2) pico, su porcentaje respecto del predicho y la pendiente ventilación minuto/ producción de dióxido de carbono (VE/VCO2). Sin embargo, ninguno de los modelos que validaron esta forma de estratificar el riesgo incluyeron la PCPE entre sus variables. Objetivos : Determinar qué proporción de pacientes con HAP del grupo I considerados de bajo riesgo y que caminan >440 metros en la prueba de caminata de 6 minutos (PC6M) tienen en la PCPE parámetros considerados de riesgo moderado o alto. Material y métodos : Se incluyeron pacientes >18 años con diagnóstico de HAP del grupo I considerados de bajo riesgo con una PC6M >400 metros a los que se les realizó una PCPE en la que se registró el VO2 pico, su porcentaje respecto del VO2 predicho y la pendiente VE/VCO2. Se determinó qué proporción de pacientes presentaban estos parámetros en un estrato de riesgo mayor a bajo riesgo (VO2 pico <15 ml/kg/min, su porcentaje respecto del predicho <65% y la pendiente VE/VCO2 >36). Resultados : Se incluyeron 18 pacientes. A pesar de ser pacientes de bajo riesgo y con buena clase funcional todos presentaron un VO2 pico menor al 85% del predicho, lo cual determina un deterioro al menos leve de la capacidad funcional. Un único paciente (6%) presentó los tres parámetros evaluados en bajo riesgo, 8 pacientes (44%) tuvieron al menos un parámetro alterado, 7 pacientes (39%) presentaron 2 parámetros alterados y en 2 pacientes (11%) todos los parámetros estuvieron alterados. Los parámetros que más frecuentemente se vieron alterados fueron el porcentaje respecto del VO2 predicho y la pendiente VE/VCO2, en el 67% de los casos. Solo 4 pacientes presentaron un VO2 pico <15 ml/k/m. Ningún paciente presentó valores de VO2 pico o porcentaje respecto del predicho en la categoría de alto riesgo. Sin embargo, 6 pacientes (33%) presentaron una pendiente VE/VCO2 considerada de alto riesgo. Conclusión : El 94% de los pacientes considerados de bajo riesgo presentaron al menos una variable en la PCPE que no corresponde a un perfil de riesgo bajo. La pendiente VE/VCO2 y el porcentaje de VO2 pico respecto del predicho fueron las variables más frecuentemente alteradas. La pendiente VE/VCO2 fue la única que mostró valores considerados de alto riesgo. La PCPE podría tener un lugar en la estratificación de precisión de pacientes de bajo riesgo. El valor de este hallazgo deberá ser evaluado en estudios prospectivos, al tiempo que genera las bases para el planteo de hipótesis respecto de la estratificación de riesgo y la intensidad del tratamiento en pacientes que aparentan estar en bajo riesgo.

ABSTRACT Background : European guidelines for pulmonary arterial hypertension (PAH) stratify the risk using clinical characteristics and complementary studies, including the cardiopulmonary exercise test (CPET). This takes into account 3 parameters: peak O2 consumption (peak VO2), its percentage with respect to the predicted VO2, and the minute ventilation/carbon dioxide production (VE/VCO2) slope. However, none of the models that validated this way of stratifying risk included PCPE among their variables. Objectives : To determine what proportion of patients with group I PAH considered to be at low risk and who walk >440 meters in the 6-minute walk test (6MWT) have parameters considered to be of moderate or high risk in the PCPE. Methods : Patients >18 years of age, diagnosed with group I PAH at low risk of events, who walked >440 meters in the 6MWT and had NT-proBNP value <300 pg/dL were included. A CPET was performed in which the peak VO2, its percentage with respect to the predicted VO2, and the VE/VCO2 slope were recorded. It was determined what proportion of patients presented these parameters in a higher than low risk stratum (peak VO2 consumption ≤15 ml/min/Kg, its percentage with respect to the predicted VO2 ≤65% and the VE/VCO2 slope ≥36). Results : Eighteen patients were included. Despite being low-risk patients with a good functional class, all patients presented a peak VO2 less than 85% of predicted, which determines a deterioration of functional capacity. A single patient (6%) presented the three parameters evaluated at low risk, 8 patients (44%) had at least one altered parameter, 7 patients (39%) presented 2 altered parameters and in 2 patients (11%) all parameters were altered. The parameters that were most frequently altered were the percentage of predicted peak VO2 and the VE/VCO2 slope in 67% of the cases. Only 4 patients presented a peak VO2 <15 ml/kg/m. No patient presented peak VO2 values or percentage of predicted VO2 in the high-risk category. However, 6 patients (33%) presented a high-risk VE/VCO2 slope. Conclusion : Majority (92%) of the patients considered low risk and who walk more than 440 meters in 6 minutes presented at least one altered variable in the CPET. The VE/VCO2 slope and the percentage of predicted peak VO2 consumption were the most frequently altered variables. The VE/VCO2 slope was the only one that showed values considered high risk. CPET could have a place in the precision stratification of low-risk patients. The value of this finding should be evaluated in prospective studies.

Hipertensión pulmonar: señalización mediada por canales de calcio, dianas farmacológicas presentes y futuras / Pulmonary hypertension: calcium channel-mediated signaling, present and future pharmacological targets

La hipertensión arterial pulmonar se caracteriza por una presión arterial pulmonar media y resistencia vascular pulmonar elevadas y remodelado patológico de las arterias pulmonares. La entrada de calcio desde el espacio extracelular al intracelular a través de canales dependientes e independientes de voltaje juega un rol fundamental en el aumento de la contractilidad de las arterias pulmonares y la pérdida de regulación del comportamiento proliferativo de las células de las distintas capas de la pared de las arterias pulmonares. De esta manera, estos canales contribuyen con la vasoconstricción exacerbada de las arterias pulmonares y a su remodelado patológico. El objetivo de esta revisión es recapitular la evidencia obtenida desde modelos celulares y animales respecto a la contribución de los principales canales de calcio de membrana plasmática en estos mecanismos fisiopatológicos claves en el desarrollo de la hipertensión pulmonar, discutiendo su valor potencial como diana farmacológica para terapias presentes y futuras.

Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.

Outcome of moderate-severe tricuspid regurgitation after pulmonary endarterectomy or balloon pulmonary angioplasty.

INTRODUCTION AND OBJECTIVES: The management of persistent moderate-severe tricuspid regurgitation (TR) in patients with chronic thromboembolic pulmonary hypertension after treatment with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) is not well defined. This study aimed to analyze the progression and predictors of significant persistent postintervention TR and its prognostic impact. METHODS: This single-center observational study included 72 patients undergoing PEA and 20 who completed a BPA program with a previous diagnosis of chronic thromboembolic pulmonary hypertension and moderate-to-severe TR. RESULTS: The postintervention prevalence of moderate-to-severe TR was 29%, with no difference between the PEA- or BPA-treated groups (30.6% vs 25% P=.78). Compared with patients with absent-mild postprocedure TR, those with persistent TR had higher mean pulmonary arterial pressure (40.2±1.9 vs 28.5±1.3mmHg P <.001), pulmonary vascular resistance (472 [347-710] vs 282 [196-408] dyn.s/cm5; P <.001), and right atrial area (23.0 [21-31] vs 16.0 [14.0-20.0] P <.001). The variables independently associated with persistent TR were pulmonary vascular resistance> 400 dyn.s/cm5 and postprocedure right atrial area> 22cm2. No preintervention predictors were identified. The variables associated with increased 3-year mortality were residual TR and mean pulmonary arterial pressure> 30mmHg. CONCLUSIONS: Residual moderate-to-severe TR following PEA-PBA was associated with persistently high afterload and unfavorable postintervention right chamber remodeling. Moderate-to-severe TR and residual pulmonary hypertension were associated with a worse 3-year prognosis.

Role of the femoral vein doppler in acute heart failure patients: results from a prospective multicentric study.

BACKGROUND AND OBJECTIVE: The aim of our study is to define the role of Pulsed-Doppler (PW-Doppler) Ultrasound of the Common Femoral Vein (CFV) in the assessment of dilatation Inferior Vena Cava (IVC), probability of Pulmonary Hypertension (PH), Tricuspid Regurgitation (TR), and Tricuspid annular plane systolic excursion (TAPSE). METHODS: This is a prospective two-hospital study in 74 patients admitted with acute heart failure (AHF). We performed PW-Doppler ultrasound of the common femoral vein, Point of Care (POC) cardiac ultrasonography and assessment of the IVC at the time of admission, as well as PW-Doppler and ultrasound of the IVC at hospital discharge. RESULTS: The detection of a pulsatile flow (138 scans) had an excellent ROC curve for the detection of IVC greater than 2cm (AUC 0.931, Sn 95%, Sp 90%, PPV 93%, NPV 94%) with an Odds Ratio (OR) of 211.2 (95% confidence interval 48.13-926.72). The pulsatility of the flow also had the highest performance in the detection of PH (AUC 0.8, Sn 95%, Sp 64%, PPV 84%, NPV 84%) and in the detection of moderate-severe TR (AUC 0.79, Sn 95%, Sp 67%, PPV 88%, NPV 78%). If the flow is continuous, we can reasonably rule out diminished TAPSE (NPV 89%). CONCLUSSION: Detection of PW-Doppler flow of the CFV may be an alternative window for the detection of an IVC dilation of 2cm, significant TR, and the likelihood of high PH in acute heart failure. It also allows us to reasonably rule out dysfunction of the right ventricle in cases of normality in these patients.