Chronic thromboembolic pulmonary hypertension: A comprehensive review of pathogenesis, diagnosis, and treatment strategies.

Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist.

Pulmonary arterial hypertension: Navigating the pathways of progress in diagnosis, treatment, and patient care.

Pulmonary arterial hypertension (PAH) is a form of precapillary pulmonary hypertension caused by a complex process of endothelial dysfunction and vascular remodeling. If left untreated, this progressive disease presents with symptoms of incapacitating fatigue causing marked loss of quality of life, eventually culminating in right ventricular failure and death. Patient management is complex and based on accurate diagnosis, risk stratification, and treatment initiation, with close monitoring of response and disease progression. Understanding the underlying pathophysiology has enabled the development of multiple drugs directed at different targets in the pathological chain. Vasodilator therapy has been the mainstay approach for the last few years, significantly improving quality of life, functional status, and survival. Recent advances in therapies targeting dysfunctional pathways beyond endothelial dysfunction may address the fundamental processes underlying the disease, raising the prospect of increasingly effective options for this high-risk group of patients with a historically poor prognosis.

Cardiovascular risk assessment using SCORE2 in a population with hypertension - the reality at a primary health care unit.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Portugal, thus it is important to identify individuals at risk. Patients with hypertension have an increased risk of adverse cardiovascular (CV) events. The role of LDL cholesterol (LDL-C) in atherosclerotic CVD is well-established. SCORE2, a new CV risk calculation tool, is used to predict the 10-year risk of fatal or non-fatal CVD. The aim of this study was to understand the impact of SCORE2 on CV risk assessment in a population with hypertension from a moderate risk country, compared to the previously used SCORE. METHODS: This observational cross-sectional study analyzed a population census of 3146 patients diagnosed with hypertension without complications (K86). After applying inclusion and exclusion criteria, 654 patients were included. Data from medical records were collected to calculate and compare SCORE and SCORE2 categories and LDL-C targets. RESULTS: Patients were classified into SCORE categories: 188 (28.75%) low, 448 (68.5%) moderate, 17 (2.6%) high and 1 (0.15%) very high risk. Using SCORE2, individuals in the SCORE low risk category were reclassified, requiring new targets: 149 individuals (80%) as low to moderate and 39 (20%) as high risk. These differences became more evident when considering SCORE moderate and high-risk categories, where 358 patients (77%) received a higher CV risk categorization, and therefore a lower LDL-C target. There was a significant increase in individuals failing to meet the target when using SCORE2, compared to SCORE (p<0.001). CONCLUSION: These findings support the importance of CV risk assessment using SCORE2 algorithm in patients with hypertension.

Evaluating the efficacy and safety of rivaroxaban as a warfarin alternative in chronic thromboembolic pulmonary hypertension patients undergoing pulmonary endarterectomy: A randomized clinical trial.

BACKGROUND AND AIM: Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by the obstruction of the main pulmonary artery due to thrombosis and vascular remodeling. Regarding the need for anticoagulant therapy in CTEPH patients, this study aimed to compare rivaroxaban with warfarin in terms of its efficacy and safety in patients undergoing endarterectomy surgery. METHODS: The study was a parallel clinical trial in patients who underwent endarterectomy following CTEPH. A total of 96 patients were randomly selected and assigned to two groups: warfarin-treated (control) and rivaroxaban-treated (intervention). Patients were clinically assessed for re-thrombosis, re-admission, bleeding, and mortality in the first, third, and sixth months after surgery. RESULTS: There was no significant difference in the occurrence of thrombosis between the two groups within the first, third-, and sixth-months post-surgery (p=0.52, 1, 0.38 respectively). Moreover, the mortality rate (p=0.9), bleeding rate (p=0.06), and re-admission rate (p=0.15) showed no significant differences between the two groups. CONCLUSION: Rivaroxaban may be as effective as warfarin in treating CTEPH patients after endarterectomy in the short term and can be used as an anticoagulant in these patients. However, studies with long-term follow-ups are needed to consolidate the strategy of treating these patients with rivaroxaban.

Prevalence and predictors of chronic thromboembolic pulmonary hypertension following severe forms of acute pulmonary embolism.

INTRODUCTION AND OBJECTIVES: The true prevalence of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) in the Portuguese population remains unknown. We aimed to assess the prevalence and predictors of CTEPH two years after a symptomatic high- (HR) or intermediate-high risk (IHR) PE. METHODS: We conducted a retrospective cohort study of patients admitted with PE between 2014 and 2019 to a Portuguese referral center for pulmonary hypertension. RESULTS: In this single-center registry of 969 patients admitted with PE (annual incidence of 46/100000 population), 194 had HR (5.4%) and IHR (14.7%) PE. After excluding patients who died or had no follow-up in the first three months, 129 patients were included in the analysis. The overall prevalence of suspected CTEPH by clinical assessment, Doppler echocardiography and V/Q lung scan was 6.2% (eight patients). CTEPH was confirmed by right heart catheterization in four of these (3.1%). Increased pulmonary artery systolic pressure (PASP) at admission (OR 1.12; 95% CI 1.04-1.22; p=0.005) and the presence of varicose veins in the lower limbs (OR 7.47; 95% CI 1.53-36.41; p=0.013) were predictors of CTEPH. PASP >60 mmHg at admission identified patients with CTEPH at follow-up with sensitivity and specificity of 83.3% and 76.3%, respectively. All patients diagnosed with CTEPH had at least two radiological findings suggestive of CTEPH at the index event. CONCLUSIONS: In our cohort, the prevalence of CTEPH in survivors of severe forms of acute PE was 6.2%. PASP above 60 mmHg and supporting radiological findings on the index computed tomography scan are highly suggestive of acute-on-chronic CTEPH.

The PERInatal MYocardial Remodeling (PERIMYR) cohort study protocol: A prospective study of cardiac remodeling and "recovery" in pregnancy as a model to understand the impact of comorbidities in cardiac remodeling and reverse remodeling.

INTRODUCTION: Heart failure (HF) is among the leading causes of morbidity and mortality worldwide. Several conditions trigger left ventricular chronic pressure or volume overload, hypertrophy, systolic and diastolic dysfunction, leading to cardiac remodeling and a rapid progression toward HF. Therapeutic interventions elicit reverse remodeling (RR), a highly variable myocardial response that ranges from none to total ventricular structural/functional recovery. However, HF patients present several comorbidities and medications that mask a comprehensive molecular knowledge of RR and hinder the identification of potential biomarkers of its progression or prognosis. Therefore, instead of using this heterogeneous population or even animal models to understand myocardial remodeling, we propose studying pregnancy-induced cardiovascular remodeling and postpartum-induced RR. OBJECTIVES: To assess cardiovascular functional and structural adaptations during pregnancy and in postpartum, characterizing the associated molecular changes; as well as to explore the impact of hypertension, obesity and diabetes on these processes. METHODS: We will perform echocardiography and assess endothelial function and arterial stiffness (EndoPAT® and pulse wave velocity, respectively) and assess potential markers of remodeling and RR using plasma and urine samples from pregnant women. To translate to a HF context, we will determine the impact of risk factors (hypertension, obesity and diabetes) by studying subgroups of pregnant women with these comorbidities. RESULTS: Not applicable. CONCLUSION: We are convinced that understanding the impact of these comorbidities in such a homogeneous population, such as pregnant women, provides a valuable model to unveil the most relevant pathologic and often masked signaling pathways underlying cardiac remodeling and incomplete RR in a heterogeneous population, such as HF patients. Moreover, we expect to identify potential novel biomarkers of RR progression/prognosis more easily.

Practical approach to referral from primary health care to a cardiology hospital consultation in 2022.

In Portugal, up to 38% of the population has cardiovascular disease, which highlights the importance of primary health care (PHC) in its management. Adequate management of people with cardiovascular disease often requires hospital referral for a cardiology consultation. However, it is not always easy to ascertain which situations should be referred, especially given that PHC does not have access to all diagnostic exams recommended by international guidelines, such as natriuretic peptides in heart failure or computed tomography coronary angiogram in chronic coronary syndromes, among others. The aim of this document is to describe a practical approach to the most frequent heart diseases that may require a referral for a hospital cardiology consultation. Thus, in the different chapters, the recommendations for referral are highlighted generically according to group of disease, as well as, albeit briefly, the initial clinical approach within the scope of PHC for a differential diagnosis and more efficient follow-up. A modified Metaplan methodology was used. A panel of 4 cardiology specialists and 3 specialists in General and Family Medicine developed this document, which should not be taken as an official guideline, but as additional guidance for the correct referral of patients. It is therefore advisable to validate these recommendations locally with the referral hospital, as well as to be aware of the respective international and national guidelines.

Relationship between oxytocin receptor gene polymorphism and hypertension in Turkish population.

INTRODUCTION AND OBJECTIVES: Known to play a key role in uterine contraction and milk ejection, the neuropeptide, oxytocin, has cardiovascular effects. To date, the known cardiovascular effects of oxytocin are blood pressure lowering (caused by natriuresis and atrial natriuretic peptide release), negative inotropic and chronotropic effect caused by parasympathetic neuromodulation, anti-stress effect and vasodilation mediated by activation of the nitric oxide pathway. The clinical significance of the rs2268498 polymorphism in oxytocin receptors in these effects is controversial. Based on the known genetic inheritance of hypertension, our research aimed to determine whether the presence of the rs2268498 oxytocin receptor (OXTR) allele C affects hypertension in our region. METHODS: This article is a case-control study conducted in the Turkish population. About 140 normotensive and 140 isolated hypertensive volunteers included in the research and genotyped with real-time PCR hybridization method via melt curve analysis. RESULTS: Oxytocin receptor rs2268498 polymorphism was assessed in terms of the risk of hypertension and hypertensive individuals were compared to the control group. OXTR rs2268498 polymorphism was not found to be a significant risk factor for dominant, recessive and additive modeled hypertension (ORdominant: 0.966, 95% CI: 0.57-1.61, p: 0.9; ORrecessive: 1, 95% CI: 0.58-1.71, p: 1.0 and ORoverall: 0.98, chi2=0.01). CONCLUSION: We concluded that rs2268498 single nucleotide polymorphism is not a risk factor for hypertension in our region.

Evaluation of a sample of Portuguese hypertensive patients' knowledge about hypertension and its influence on their beliefs and adherence to therapy.

INTRODUCTION AND OBJECTIVES: Patient knowledge about hypertension is an important patient-related determinant for poor blood pressure control and is a target for more effective interventions. We aimed to evaluate hypertensive patients' knowledge and awareness about hypertension and its influence on their beliefs about their medication and their adherence to antihypertensive therapy. METHODS: A cross-sectional study was conducted among adult patients attending one of the participating pharmacies and taking at least one antihypertensive drug. Data on personal and family history were collected, and Portuguese versions of the Hypertension Knowledge Test (HKT), Beliefs about Medicines Questionnaire (BMQ), and short version of the Maastricht Utrecht Adherence in Hypertension questionnaire (MUAH-16) were administered. RESULTS: A total of 240 patients were enrolled. The mean number of antihypertensive drugs used was 1.62±0.99, with 15.4% of patients treated with three or more drugs. More than 80% of patients knew the blood pressure therapeutic goals and identified overweight, sedentary lifestyle, and salt as risk factors for hypertension. Conversely, the majority of the patients were not aware of the asymptomatic characteristics of hypertension and believed that antihypertensive treatment had to be used for a limited time duration. Negative and significant correlations were found between the HKT and negative attitudes toward medication, but no association was found with positive attitudes. CONCLUSIONS: Hypertensive patients had good knowledge of hypertension risk factors but not of antihypertensive treatment. Increasing patient knowledge about hypertension may possibly reduce negative attitudes toward medication but will probably have no impact on positive attitudes.

Renal sympathetic denervation in resistant hypertension: The association between vitamin D and positive early response in systolic blood pressure.

AIMS AND OBJECTIVES: Vitamin D deficiency is a common finding and there is a suggested association with hypertension. Resistant hypertension is a clinical problem observed in 5-30% of hypertensive patients. Renal denervation (RDN) has been used for patients with resistant hypertension and has proven to lower blood pressure. Our primary goal was to assess the vitamin D serum concentration as a predictor of blood pressure response to RDN in highly selected patients. METHODS: This prospective, nonrandomized, single-center study included 24 patients treated with RDN. Based on their one-year response after RDN, patients were classified as responders or non-responders at six months or at 12 months. RESULTS: The median follow-up was 52 months (range, 14-91 months). After RDN, 17 patients (70.8%) had a reduction >5 mmHg in the mean systolic blood pressure, at the first six months of follow-up. At 12 months, 20 patients (83.3%) were responders. Vitamin D levels at baseline (15.1±4.8 vs. 24.2±8.8 ng/ml) and at six months (16.6±7.2 vs. 25±9.2 ng/ml) were lower in early non-responders compared to early responders (p=0.008), without significant variation during follow-up. Even though Vitamin D levels were lower in the total responder's group, no statistically significant differences were found (p=ns). CONCLUSION: In patients with resistant hypertension, low vitamin D concentrations were associated with an absence of early response to RDN.

Chronic thromboembolic pulmonary hypertension: A 10-year analysis from a Portuguese referral center.

INTRODUCTION AND OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive, but potentially curable, form of pulmonary hypertension. Pulmonary endarterectomy (PEA) is a complex surgery that frequently achieves hemodynamic normalization and symptom resolution, although not all patients are suitable for the procedure. We aimed to assess long-term outcomes of CTEPH, namely all-cause mortality and hospital admission for decompensated heart failure, according to treatment modalities in patients who underwent PEA or non-surgical therapy. METHODS: A 10-year retrospective study of patients with CTEPH at a referral center was conducted. Forty-five patients were included and median follow-up time was 57 (IQR 24-93) months. Survival analysis was performed and a multivariate Cox regression model was used to identify independent predictors of outcomes. RESULTS: Patients were mostly female (59%) and mean age was 63±16 years. Two-thirds were severely symptomatic at diagnosis, with 62.2% of patients presenting in WHO functional class (WHO FC) III or IV. One-, two- and three-year survival was 93.3%, 82.4% and 75.9%, respectively. Serum BNP (HR 1.003; 95% CI: 1.001-1.005; p=0.003) and creatinine (HR 12.092; 95% CI: 1.121-130.390; p=0.040) were predictors of death. Mortality was numerically lower in those who underwent PEA (p=0.135). PEA was associated with decreased risk of the combined endpoint of all-cause mortality and hospital admission for decompensated heart failure (HR 0.198; 95% CI: 0.040-0.982; p=0.047), as were lower serum BNP (HR 1.003; 95% CI: 1.001-1.005; p=0.008) and mPAP (HR 1.073; 95% CI: 1.022-1.128; p=0.005) at diagnosis. Most patients who underwent PEA presented improved WHO FC (92.9%) and post-surgical residual pulmonary hypertension was identified in only 21.4%. CONCLUSION: PEA provided a better overall prognosis than non-surgical therapy, improving symptoms and frequently achieving hemodynamic normalization, with a numerical trend for lower mortality. Higher serum BNP, creatinine and mPAP at diagnosis were independently associated with worse outcomes.

Neurofibromatosis type 1 and pulmonary arterial hypertension: A case report.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder that affects multiple organ systems and has a wide range of clinical manifestations. Pulmonary hypertension (PH) associated with NF1 (PH-NF1) is rarely seen, but confers a dismal prognosis. In the literature this association has been described in only 31 cases. The authors report the case of a 77-year-old female patient with NF1 complicated by severe precapillary PH despite triple disease-specific oral combination therapy. Because no data are available on the efficacy of specific PH therapy in PH-NF1, these patients should be assessed in expert PH centers and referred for lung transplantation at an early stage.

Ruptured sinus of Valsalva aneurysm: A reversible cause of suprasystemic pulmonary hypertension.

Management of patients with congenital heart defects and associated pulmonary arterial hypertension remains a major concern. With evolving targeted drug therapies and new iterations of transcatheter devices, treatment of appropriately selected patients with severe pulmonary hypertension, classically considered inoperable, has become feasible. We report the case of a patient with concomitant ruptured right sinus of Valsalva aneurysm and ventricular septal defect, with early reversal of suprasystemic pulmonary pressures following successful percutaneous closure of ruptured sinus of Valsalva.

Chest pain in a patient with pulmonary arterial hypertension.

Chest pain is a frequent symptom in patients with pulmonary arterial hypertension (PAH). Left main coronary artery (LMCA) extrinsic compression from a pulmonary artery (PA) is an increasingly recognized cause of angina or complications, such as acute myocardial infarction, left ventricular dysfunction, arrythmia, and sudden death. We report the case of a 45-year-old patient with pre-capillary pulmonary hypertension (PH), a patent ductus arteriosus corrected surgically during adolescence, and chronic constrictive bronchiolitis. In 2016, the patient began to report oppressive chest pain and worsening fatigue. Computed tomography coronary angiography (CTCA) showed extrinsic LMCA compression by a dilated PA, which was confirmed by invasive coronary angiography and intravascular ultrasound. After stent implantation, the patient reported symptom resolution, and has been asymptomatic ever since. Imaging studies, in particular CTCA, play an important role in the diagnosis of LMCA compression in patients with PAH. The reported case supports the efficacy and safety of stent implantation as a therapeutic option, as already demonstrated in the literature. It shows the complexity of decision making on the operability of systemic-to-pulmonary shunts and reinforces the importance of continuous diagnostic testing.

Safety and efficacy of balloon pulmonary angioplasty in a Portuguese pulmonary hypertension expert center.

INTRODUCTION: Balloon pulmonary angioplasty (BPA) is an alternative therapy in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or residual/recurrent pulmonary hypertension (PH) after surgery. The aim of this study was to assess the short-term efficacy and safety of a BPA program. METHODS: This prospective single-center study included all BPA sessions performed in CTEPH patients between 2017 and 2019. Clinical assessment including WHO functional class, plasma biomarkers, 6-min walk test (6MWT) and right heart catheterization was performed at baseline and six months after the last BPA session. RESULTS: A total of 57 BPA sessions were performed in 11 CTEPH patients (64% with inoperable disease, 82% under pulmonar vasodilator therapy). Nine patients completed both the BPA program and a minimum six-month follow-up period. There were significant improvements in WHO functional class (p=0.004) and 6MWT (mean increase of 42 m; p=0.050) and a trend for significant hemodynamic improvement: 25% decrease in mean pulmonary artery pressure (mPAP) (p=0.082) and 42% decrease in pulmonary vascular resistance (PVR) (p=0.056). In the group of patients with severely impaired hemodynamics (three patients with mPAP >40 mmHg), the reduction was significant: 51% in mPAP (p=0.013) and 67% in PVR (p=0.050). Prostacyclin analogs and long-term oxygen therapy were withdrawn in all patients. Minor complications were recorded in 25% of patients. There were no major complications or deaths. CONCLUSIONS: A BPA strategy on top of pulmonary vasodilator therapy further improves symptoms, exercise capacity and hemodynamics with an acceptable risk-benefit ratio in patients with inoperable CTEPH or residual/recurrent PH after surgery.

Chronic thromboembolic pulmonary hypertension: Initial experience of patients undergoing pulmonary thromboendarterectomy.

INTRODUCTION AND OBJECTIVES: Pulmonary endarterectomy (PEA) is a potentially curative procedure in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study reports the initial experience of a Portuguese PH center with patients undergoing PEA at an international surgical reference center. METHODS: Prospective observational study of consecutive CTEPH patients followed at a national PH center, who underwent PEA at an international surgical reference center between October 2015 and March 2019. Clinical, functional, laboratory, imaging and hemodynamic parameters were obtained in the 12 months preceding the surgery and repeated between four and six months after PEA. RESULTS: 27 consecutive patients (59% female) with a median age of 60 (49-71) years underwent PEA. During a median follow-up of 34 (21-48) months, there was an improvement in functional class in all patients, with only one cardiac death. From a hemodynamic perspective, there was a reduction in mean pulmonary artery pressure from 48 (42-59) mmHg to 26 (22-38) mmHg, an increase in cardiac output from 3.3 (2.9-4.0) L/min to 4.9 (4.2-5.5) L/min and a reduction in pulmonary vascular resistance from 12.1 (7.2-15.5) uW to 3.5 (2.6-5,2) uW. During the follow-up, 44% (n=12) of patients had no PH criteria, 44% (n=12) had residual PH and 11% (n=3) had PH recurrence. There was a reduction of N-terminal pro-B-type natriureticpeptide from 868 (212-1730) pg/mL to 171 (98-382) pg/mL. Rright ventricular systolic function parameters revealed an improvement in longitudinal systolic excursion and peak velocity of the plane of the tricuspid ring from 14 (13-14) mm and 9 (8-10) cm/s to 17 (16-18) mm and 13 (11-15) cm/s, respectively. Of the 26 patients with preoperative right ventricular dysfunction, 85% (n=22) recovered. The proportion of patients on specific vasodilator therapy decreased from 93% to 44% (p<0.001) and the proportion of those requiring oxygen therapy decreased from 52% to 26% (p=0.003). The six-minute walk test distance increased by about 25% compared to the baseline and only eight patients had significant desaturation during the test. CONCLUSION: Pulmonary endarterectomy performed at an experienced high-volume center is a safe procedure with a very favorable medium-term impact on functional, hemodynamic and right ventricular function parameters in CTEPH patients with operable disease. It is possible for PH centers without PEA differentiation to refer patients safely and effectively to an international surgical center in which air transport is necessary.

Balloon pulmonary angioplasty protocol in a Portuguese pulmonary hypertension expert center.

INTRODUCTION: Balloon pulmonary angioplasty (BPA) has emerged as a promising therapeutic option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not eligible for pulmonary thromboendarterectomy (PEA) or who have recurrent or persistent pulmonary hypertension after surgery. There is no standardized technique for BPA and, its complexity and high risk of severe complications, requires skills and appropriate training and should be reserved for expert CTEPH centers, as a complementary intervention to medical and surgical therapy. OBJECTIVE: The purpose of this document is to describe the BPA protocol used at a high-volume center nationwide, validated by its results. METHODS: The present protocol includes technical details, definition of outcomes and complications, as well as patient full diagnostic work-up and treatment algorithm, before and after BPA. RESULTS: The technical, hemodynamic, and clinical results of the application of this protocol will be subject of a later publication where they will be described in detail. In conclusion, we present a percutaneous intervention protocol in the treatment of pulmonary hypertension in the context of chronic pulmonary thromboembolism, validated by its clinical, hemodynamic, and technical results.

Safety and efficacy of balloon pulmonary angioplasty in a Portuguese pulmonary hypertension expert center. / Segurança e eficácia da angioplastia pulmonar por balão em Portugal num centro de referência em hipertensão pulmonar.

INTRODUCTION: Balloon pulmonary angioplasty (BPA) is an alternative therapy in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or residual/recurrent pulmonary hypertension (PH) after surgery. The aim of this study was to assess the short-term efficacy and safety of a BPA program. METHODS: This prospective single-center study included all BPA sessions performed in CTEPH patients between 2017 and 2019. Clinical assessment including WHO functional class, plasma biomarkers, 6-min walk test (6MWT) and right heart catheterization was performed at baseline and six months after the last BPA session. RESULTS: A total of 57 BPA sessions were performed in 11 CTEPH patients (64% with inoperable disease, 82% under pulmonary vasodilator therapy). Nine patients completed both the BPA program and a minimum six-month follow-up period. There were significant improvements in WHO functional class (p=0.004) and 6MWT (mean increase of 42 m; p=0.050) and a trend for significant hemodynamic improvement: 25% decrease in mean pulmonary artery pressure (mPAP) (p=0.082) and 42% decrease in pulmonary vascular resistance (PVR) (p=0.056). In the group of patients with severely impaired hemodynamics (three patients with mPAP >40mmHg), the reduction was significant: 51% in mPAP (p=0.013) and 67% in PVR (p=0.050). Prostacyclin analogs and long-term oxygen therapy were withdrawn in all patients. Minor complications were recorded in 25% of patients. There were no major complications or deaths. CONCLUSIONS: A BPA strategy on top of pulmonary vasodilator therapy further improves symptoms, exercise capacity and hemodynamics with an acceptable risk-benefit ratio in patients with inoperable CTEPH or residual/recurrent PH after surgery.

Chronic thromboembolic pulmonary hypertension: initial experience of patients undergoing pulmonary thromboendarterectomy. / Hipertensão pulmonar tromboembólica crónica: experiência inicial de doentes submetidos a tromboendarterectomia pulmonar.

INTRODUCTION AND OBJECTIVES: Pulmonary endarterectomy (PEA) is a potentially curative procedure in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study reports the initial experience of a Portuguese PH center with patients undergoing PEA at an international surgical reference center. METHODS: Prospective observational study of consecutive CTEPH patients followed at a national PH center, who underwent PEA at an international surgical reference center between October 2015 and March 2019. Clinical, functional, laboratory, imaging and hemodynamic parameters were obtained in the 12 months preceding the surgery and repeated between four and six months after PEA. RESULTS: 27 consecutive patients (59% female) with a median age of 60 (49-71) years underwent PEA. During a median follow-up of 34 (21-48) months, there was an improvement in functional class in all patients, with only one cardiac death. From a hemodynamic perspective, there was a reduction in mean pulmonary artery pressure from 48 (42-59) mmHg to 26 (22-38) mmHg, an increase in cardiac output from 3.3 (2.9-4.0) L/min to 4.9 (4.2-5.5) L/min and a reduction in pulmonary vascular resistance from 12.1 (7.2-15.5) uW to 3.5 (2.6-5, 2) uW. During the follow-up, 44% (n=12) of patients had no PH criteria, 44% (n=12) had residual PH and 11% (n = 3) had PH recurrence. There was a reduction of N-terminal pro-B-type natriureticpeptide from 868 (212-1730) pg/mL to 171 (98-382) pg/mL. Rright ventricular systolic function parameters revealed an improvement in longitudinal systolic excursion and peak velocity of the plane of the tricuspid ring from 14 (13-14) mm and 9 (8-10) cm/s to 17 (16-18) mm and 13 (11-15) cm/s, respectively. Of the 26 patients with preoperative right ventricular dysfunction, 85% (n=22) recovered. The proportion of patients on specific vasodilator therapy decreased from 93% to 44% (p<0.001) and the proportion of those requiring oxygen therapy decreased from 52% to 26% (p=0.003). The six-minute walk test distance increased by about 25% compared to the baseline and only eight patients had significant desaturation during the test. CONCLUSION: Pulmonary endarterectomy performed at an experienced high-volume center is a safe procedure with a very favorable medium-term impact on functional, hemodynamic and right ventricular function parameters in CTEPH patients with operable disease. It is possible for PH centers without PEA differentiation to refer patients safely and effectively to an international surgical center in which air transport is necessary.

Dyspnea in antiphospholipid syndrome: Beyond pulmonary embolism.

Pulmonary embolism due to primary antiphospholipid syndrome is rarely associated with chronic thromboembolic pulmonary hypertension, and therefore according to the latest guidelines on pulmonary hypertension, routine screening is not recommended. We describe a young patient with a late diagnosis of chronic thromboembolic pulmonary hypertension in the context of pulmonary embolism, primary antiphospholipid syndrome and suboptimal anticoagulation. Of note, mild cardiopulmonary symptoms were consistently misattributed to a depressive disorder because physical examination was normal, serial Doppler echocardiography failed to show pulmonary hypertension, and all other diagnostic tests were normal. Once symptoms became severe, positive screening tests led to the correct diagnosis and surgical referral, and bilateral pulmonary endarterectomy was successfully performed. This case demonstrates the need for extra awareness in patients with antiphospholipid syndrome and pulmonary embolism.