Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era.

BACKGROUND: The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH. METHODS: We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e. monotherapy versus combination therapy). RESULTS: There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53). CONCLUSIONS: There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.

Evaluation of Lung Glucose Uptake with Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/CT in Patients with Pulmonary Arterial Hypertension and Pulmonary Hypertension Due to Left Heart Disease.

Aim: Previous studies have demonstrated increased glucose uptake by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in lung parenchyma in animal models or small pulmonary arterial hypertension (PAH) cohorts. However, it is not well known whether increased FDG uptake in the lung is a unique phenomenon in PAH or whether elevated pulmonary artery pressure (PAP) induces FDG uptake. Methods and results: Nineteen patients with PAH, 8 patients with pulmonary hypertension due to left heart disease (PH-LHD), and 14 age matched control subjects were included. All PH patients underwent right heart catheterization and FDG-PET. The mean standard uptake value (SUV g/mL) of FDG in each lung was obtained and average values of both lungs were calculated as mean lung FDG SUV. The correlation between hemodynamics and mean lung FDG SUV was also analyzed in PH patients. Mean PAP (mPAP) was not significantly different between PAH and PH-LHD (45±11 vs 43±5 mmHg, p=0.51). PAH patients demonstrated significantly increased mean lung FDG SUV compared with PH-LHD and controls (PAH: 0.76±0.26 vs PH-LHD: 0.51±0.12 vs controls: 0.53±0.16, p=0.0025). The mean lung FDG SUV did not correlate with mPAP either in PAH or PH-LHD. Conclusion: PAH is associated with increased lung FDG uptake indicating increased glucose utilization in the lung. This may represent metabolic shift to glycolysis and/or active inflammation in the remodeled pulmonary vasculature, and is observed to a greater extent in PAH than in patients with PH secondary to LHD and control subjects without PH.

Incorporation of renal function in mortality risk assessment for pulmonary arterial hypertension.

BACKGROUND: Risk assessment is important for prognostication and individualized treatment decisions for patients with pulmonary arterial hypertension (PAH). The purpose was (1) to compare contemporary risk assessment tools and (2) to determine the prognostic significance of risk parameters of kidney function and whether they can further improve risk prediction for patients with PAH. METHODS: We identified a cohort of treatment-naive patients (n = 211) who received an incident diagnosis of PAH at the University of Ottawa Heart Institute. Using demographics, disease characteristics, and hemodynamic data at diagnosis, we categorized patients as low, intermediate, or high risk according to current European guidelines (European Society of Cardiology [ESC]) and registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL) risk scores. The primary end-point was transplant-free survival (TFS). RESULTS: Patients were predominantly women (64.6%) with World Health Organization function Class III symptoms (66.5%). The median TFS was 7.09 years. There was little agreement between ESC- and REVEAL-based risk estimates (weighted kappa = 0.21-0.34). Although both the ESC (log-rank, p = 0.0002) and REVEAL algorithms stratified TFS risk (p < 0.0001), the REVEAL score provided superior discrimination (C-statistic = 0.70 vs 0.59, p = 0.004). Renal function at diagnosis (p < 0.0001) and Δ renal function at 6 months (p < 0.0001) were identified as novel risk parameters and served to reclassify some patients in the intermediate-risk category to a lower or higher risk stratum (p < 0.0001). CONCLUSION: REVEAL-based strategies provide superior TFS risk discrimination to ESC/European Respiratory Society-based approaches. However, the classification of intermediate-risk patients varied significantly across tools. We demonstrate the importance of renal function, which further improved the stratification of risk in patients with PAH, particularly in patients who are considered intermediate risk.

Effects of Riociguat on Right Ventricular Remodelling in Chronic Thromboembolic Pulmonary Hypertension Patients: A Prospective Study.

BACKGROUND: The effects of riociguat treatment on right ventricular (RV) metabolism, perfusion, and output in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are unknown. In this study, RV changes associated with riociguat therapy were investigated. METHODS: Six patients with CTEPH received riociguat for 6 months. Right heart catheterization (only baseline), cardiac magnetic resonance imaging, and positron emission tomography using tracers for myocardial glucose uptake (18F-fluorodeoxyglucose [18F-FDG]) and perfusion (13N-ammonia) were performed at baseline and follow-up time points. RESULTS: At baseline, median RV ejection fraction (RVEF) was 47% (22%-53%) with a mean pulmonary artery pressure (PAP) of 42 mm Hg (27-57 mmHg). Two patients were New York Heart Association functional class III and the rest were class II. Baseline RV 18F-FDG uptake was inversely correlated with RVEF (rs = -0.82; P = 0.04) and positively correlated with mean PAP (rs = 0.94; P = 0.004). Riociguat treatment was associated with a significant increase in RV stroke volume index by 13.5 mL/m2 (6.8-17.5 mL/m2; P = 0.03) and a trend of improved RVEF by 5% (1%-9%; P = 0.09). Myocardial fibrosis indicated by the volume of myocardium exhibiting late gadolinium enhancement was reduced by 4.4 mL (0.2-5.2 mL; P = 0.09). 18F-FDG (metabolism) and 13N-ammonia (perfusion) positron emission tomography did not show a significant difference over the follow-up period. The studied patients (except for 1) had a reduction in the ratio of RV 18F-FDG uptake to RV perfusion, suggesting improved RV metabolism-flow relationships. CONCLUSIONS: Riociguat treatment was associated with increased RV stroke volume index and trends for improvement in myocardial remodelling in patients with CTEPH. A larger clinical study is warranted to observe the therapeutic benefits of riociguat on RV remodelling.

Shifts in myocardial fatty acid and glucose metabolism in pulmonary arterial hypertension: a potential mechanism for a maladaptive right ventricular response.

AIMS: We investigated the role of metabolic alterations in the development of a maladaptive right ventricular (RV) response in pulmonary arterial hypertension (PAH), which has not previously been undertaken. This study evaluated relationships between glucose and fatty acid metabolism obtained using PET with invasive pulmonary haemodynamics, RV measurements, and RV function to gain insight into the mechanism of RV maladaptation. METHODS AND RESULTS: Seventeen consecutive PAH patients (mean age 56 ± 15) who underwent right heart catheterization [mean pulmonary arterial pressure (mPAP) 43 ± 12 mmHg] had cardiac 18F-fluoro-2-deoxyglucose (FDG) and (18)F-fluoro-6-thioheptadecanoic acid (FTHA) PET imaging. RV and left ventricular (LV) FDG and FTHA uptake standard uptake values (SUVs) were measured. The SUV was corrected for the partial volume effect (SUVPVE) based on cardiac magnetic resonance imaging (CMR). Right ventricular ejection fraction (RVEF) was determined by CMR. There was a significant positive correlation between mPAP and RV/LV FDG SUVPVE (r = 0.68, P = 0.003), and the ratio of RV/LV FDG SUV : RV/LV FTHA SUV (r = 0.60, P = 0.02). RVEF was negatively correlated with RV/LV FDG SUVPVE uptake (r = -0.56, P = 0.02) and RV/LV FTHA SUVPVE (r = -0.62, P = 0.019). CONCLUSION: Increased pulmonary arterial pressures are associated with increases in the ratio of FDG/FTHA uptake in the RV. Inverse correlation between the uptake of the metabolic tracers and RV function may reflect a shift towards increased fatty acid oxidation and glycolysis associated with RV failure in maladaptive remodelling.

Pulmonary hypertension due to fibrosing mediastinitis treated successfully with stenting of pulmonary vein stenoses.

We describe a patient with fibrosing mediastinitis after childhood histoplasmosis who presented with severe pulmonary hypertension secondary to pulmonary vein stenoses. Stenting of 2 stenosed pulmonary veins via a transseptal approach resulted in an immediate decrease in systolic pulmonary artery pressure from 90 to 68 mm Hg and improvement in dyspnea and cardiac index, which was sustained at 6 months. This case highlights the importance of routinely assessing the pulmonary veins during workup for pulmonary hypertension.

[All-trans retinoic acid syndrome. Case report and a review of the literature]. / Síndrome del ácido transretinoico. Reporte de un caso y revisión de la literatura.

We described a patient with acute promyelocytic leukemia (APL) who developed all-trans retinoic acid syndrome (ATRAS) and reviewed the literature. ATRAS presents in patients with APL treated with all-trans retinoic acid (ATRA). It has an incidence from 5%-27% with mortality of 29%. It is secondary to ATRA effect on promyelocyte differentiation, which causes systemic inflammatory response syndrome, endothelium damage with increase in capillary permeability, microcirculation obstruction, and tissue infiltration. ATRAS clinical manifestations are fever, hypotension, respiratory, renal and hepatic insufficiency, lung infiltrates, pleural and pericardic effusion, and generalized edema. Treatment is based on ATRA suspension, support measures, and steroids.

[Pseudothrombocytopenia induced by ethylenediaminetetraacetic acid in burned patients]. / Pseudotrombocitopenia inducida por ácido etilendiamino-tetracético en paciente con quemaduras.

The EDTA-dependent pseudothrombocytopenia is a false decrease in the number of platelets below the normal value when analyzed with automated devices. There is an incidence of 0.09 to 0.21% in hospitalized patients. Pseudothrombocytopenia is secondary to platelet clumping induced by antibodies in the presence of EDTA and has been associated with sepsis, cancer, cardiac surgery and drugs. We report the first case of pseudothrombocytopenia induced by EDTA in a burn patient.

[Persistent left superior vena cava: infrequent localization of central venous catheter]. / Vena cava superior izquierda persistente: localización infrecuente del catéter venoso central.

OBJECTIVE: Our objective was to report a Persistent Left Superior Vena Cava in a critically ill patient. DESIGN: Case report. PLACE: Intensive care unit of a referral center. PATIENT: A 52 years-old male without previous cardiovascular disease was admitted to the intensive care unit due to cranial trauma. A central left subclavian vein catheter was placed at his arrival at the center chest X-ray showed the catheter in the left of the cardiac silhohuete without hemo-pneumothorax. A angiographic evaluation through central venous catheter showed persistent left superior vena cava draining to the coronary sinus and right atrium with normal permeability of right superior vena cava. Other congenital alterations were excluded. Chest computed tomography confirmed the diagnosis. Persistent left superior vena cava is a congenital vascular abnormality. The intensive care unit staff must be aware of this vascular abnormality because it can complicate central venous catheterization.

[Non-hypothermic J wave in subarachnoid hemorrhage]. / Onda J no hipotérmica en hemorragia subaracnoidea.

Incidence of electrocardiographic abnormalities in subarachnoid hemorrhage secondary to aneurysm rupture is 50-100%. The most frequent electrocardiographic abnormalities described include acuminated, inverted or flat T waves, inverted T waves associated with prolonged QT interval, positive or negative ST segment levels, prominent U waves, PR segment enlargement, acuminated P waves, and pathologic Q waves. J point is the isoelectric union of QRS complex with ST segment. It represents the end of depolarization and the beginning of repolarization. Prominent and positive J point level is named J wave, considered pathognomonic of severe hypothermia, although it has also been described in other clinical entities not associated with hypothermia, such as hypercalcemia, Brugada syndrome, acute brain injury, cardiac arrest, and dysfunction of cervical sympathetic system. Non-hypothermic J wave is an infrequent electrocardiographic manifestation of subarachnoid hemorrhage. We describe a clinical case of non-hypothermic J wave in a patient with subarachnoid hemorrhage.

Síndrome del ácido transretinoico: Reporte de un caso y revisión de la literatura / All-Trans retinoic acid Syndrome: Case Report and a Review of the Literature

Se describe el caso de una enferma con leucemia aguda promielocítica (LAP) que desarrolló síndrome del ácido transretinoico (SATRA) y se revisa la literatura. El SA TRA se presenta en enfermos con LAP tratados con ácido transretinoico (ATRA). Tiene incidencia de 5% a 27% con mortalidad de hasta 29%. Es secundario al efecto del ATRA sobre la diferenciación de los promielocitos, lo que desencadena respuesta inflamatoria sistémica, daño endotelial con síndrome de fuga capilar y obstrucción de la microcirculación e infiltración tisular. Clínicamente se manifiesta con fiebre, hipotensión, insuficiencia respiratoria, renal y hepática, infiltrados pulmonares, derrame pleural y pericárdico, y edema generalizado. El tratamiento es a base de suspensión del ATRA, medidas de apoyo y esferoides.

We described a patient with acute promyelocytic leukemia (APL) who developed all-trans retinoic acid syndrome (ATRAS) and reviewed the literature. ATRAS presents in patients with APL treated with all-trans retinoic acid (ATRA). It has an incidence from 5%-27% with mortality of 29%. It is secondary to ATRA effect on promyelocyte differentiation, which causes systemic inflammatory response syndrome, endothelium damage with increase in capillary permeability, microcirculation obstruction, and tissue infiltration. ATRAS clinical manifestations are fever, hypotension, respiratory, renal and hepatic insufficiency, lung infiltrates, pleural and pericardic efussion, and generalized edema. Treatment is based on ATRA suspension, support measures, and steroids.