Randomized, Multicenter Study to Assess the Effects of Different Doses of Sildenafil on Mortality in Adults With Pulmonary Arterial Hypertension.

BACKGROUND: Sildenafil, approved for pulmonary arterial hypertension (PAH), has a recommended adult dose of 20 mg TID, with a previously approved 5-mg TID dose by the US Food and Drug Administration. Safety concerns arose because of common off-label use of higher doses, particularly after pediatric data linked higher doses to increased mortality. To assess this, the Food and Drug Administration mandated a study evaluating the effects of various sildenafil doses on mortality in adults with PAH. METHODS: This randomized, double-blind study compared sildenafil at doses of 5, 20, or 80 mg TID in adults with PAH. The primary objective was noninferiority of 80 mg of sildenafil versus 5 mg for all-cause mortality. Secondary end points included time to clinical worsening and change in 6-minute walk distance at 6 months. Interim analyses were planned at 50% and 75% of the anticipated mortality events. Safety and tolerability were assessed in the intention-to-treat population. RESULTS: The study was halted after the first interim analysis, demonstrating noninferiority for 80 mg of sildenafil versus 5 mg. Of 385 patients enrolled across all dose groups, 78 died. The primary analysis showed a hazard ratio of 0.51 (99.7% CI, 0.22-1.21; P<0.001 for noninferiority) for overall survival comparing 80 mg of sildenafil with 5 mg. Time to clinical worsening favored 80 mg of sildenafil compared with 5 mg (hazard ratio, 0.44 [99.7% CI, 0.22-0.89]; P<0.001). Sildenafil at 80 mg improved 6-minute walk distance from baseline at 6 months compared with 5 mg (least square mean change, 18.9 m [95% CI, 2.99-34.86]; P=0.0201). No significant differences were found between 80 mg of sildenafil and 20 mg in mortality, clinical worsening, and 6-minute walk distance. Adverse event-related drug discontinuations were numerically higher with 80 mg of sildenafil. CONCLUSIONS: Sildenafil at 80 mg was noninferior to sildenafil at 5 mg when examining all-cause mortality in adults with PAH. Secondary efficacy end points favored 80 mg of sildenafil over 5 mg. On the basis of these findings, the Food and Drug Administration recently revoked the approval of 5 mg of sildenafil for adults with PAH, reinforced 20 mg TID as the recommended dose, and now allows dose titration up to 80 mg TID, if needed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060487.

Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis.

OBJECTIVES: Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH. METHODS: We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes. RESULTS: This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34) they were 97%, 77% and 61%; for MCTD-PAH (n = 33) they were 97%, 70% and 59%; for UCTD-PAH (n = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P = 0.001). In these patients, the survival estimates were significantly better with initial ERA-PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P = 0.016 and P = 0.012, respectively). CONCLUSIONS: Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA-PDE5i combination therapy compared with initial monotherapy.

The Initial Experience of Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension in Latvia.

Background: Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent pulmonary hypertension after pulmonary endarterectomy (PEA) include targeted medical therapy and balloon pulmonary angioplasty (BPA). BPA is an emerging treatment modality that has been reported to improve functional capacity, pulmonary hemodynamics, and right ventricular function. Reports from expert centers are promising, but more data are needed to make the results more generalizable. Materials and Methods: We conducted a prospective analysis of nine consecutive CTEPH patients who underwent balloon pulmonary angioplasty (BPA) sessions at Pauls Stradins Clinical University Hospital in Riga, Latvia between 1 April 2022 and 1 July 2023. We assessed World Health Organization (WHO) functional class, 6 min walk distance (6MWD), blood oxygen saturation (SpO2), brain natriuretic peptide (BNP) level at baseline and 3 months after the first BPA session. For two patients on whom repeated BPA sessions were performed, we additionally assessed cardiac output (CO), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (mPAP). Results: A total of 12 BPA procedures for nine patients were performed; repeated BPA sessions were performed for two patients. Our results show a reduction in BNP levels and improvement in WHO functional class, 6MWD, and SpO2 after the first BPA session. Improvement in 6MWD was statistically significant. Additionally, an improvement in pulmonary hemodynamic parameters was observed. Conclusions: Our data show that BPA is an effective interventional treatment modality, improving both the pulmonary hemodynamics and functional status. Moreover, BPA is safe and excellently tolerated.

Baseline Clinical Characteristics and Incidence of Chronic Thromboembolic Pulmonary Hypertension Patients in Latvia, 2019-2020.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and progressive condition; however, the true characteristics of CTEPH are still unknown, as notable regional variations exist in terms of patients' age, baseline hemodynamic data, and management choices. This report aims to investigate the baseline clinical characteristics, incidence, and risk factors associated with CTEPH patients in Latvia from 2019 to 2020. Methods: The data were analyzed from a prospective, nationwide, Latvian pulmonary hypertension registry for incident CTEPH cases. The patients' clinical characteristics were assessed at the time of diagnosis. Results: During the course of this study, a cohort of 13 patients with CTEPH were included for analysis. Among the enrolled CTEPH patients, most exhibited low exercise and functional capacity, with a median (±IQR) 6 min walk distance of 300.0 (±150.0) m. The median values (±IQR) for mean pulmonary artery pressure and pulmonary vascular resistance were 40.0 ± 13.0 mmHg and 7.35 ± 2.82 Wood units, respectively. The most common risk factors for CTEPH were a history of acute pulmonary embolism and a blood group other than O. Conclusions: The findings of this report revealed the characteristics of the Latvian CTEPH population, indicating that a significant proportion of patients are elderly individuals with multiple comorbidities.

Temporal trends in pulmonary arterial hypertension: results from the COMPERA registry.

BACKGROUND: Since 2015, the European pulmonary hypertension guidelines recommend the use of combination therapy in most patients with pulmonary arterial hypertension (PAH). However, it is unclear to what extent this treatment strategy is adopted in clinical practice and if it is associated with improved long-term survival. METHODS: We analysed data from COMPERA, a large European pulmonary hypertension registry, to assess temporal trends in the use of combination therapy and survival of patients with newly diagnosed PAH between 2010 and 2019. For survival analyses, we looked at annualised data and at cumulated data comparing the periods 2010-2014 and 2015-2019. RESULTS: A total of 2531 patients were included. The use of early combination therapy (within 3 months after diagnosis) increased from 10.0% in patients diagnosed with PAH in 2010 to 25.0% in patients diagnosed with PAH in 2019. The proportion of patients receiving combination therapy 1 year after diagnosis increased from 27.7% to 46.3%. When comparing the 2010-2014 and 2015-2019 periods, 1-year survival estimates were similar (89.0% (95% CI 87.2-90.9%) and 90.8% (95% CI 89.3-92.4%), respectively), whereas there was a slight but nonsignificant improvement in 3-year survival estimates (67.8% (95% CI 65.0-70.8%) and 70.5% (95% CI 67.8-73.4%), respectively). CONCLUSIONS: The use of combination therapy increased from 2010 to 2019, but most patients still received monotherapy. Survival rates at 1 year after diagnosis did not change over time. Future studies need to determine if the observed trend suggesting improved 3-year survival rates can be confirmed.

Individually Tailored Remote Physiotherapy Program Improves Participation and Autonomy in Activities of Everyday Life along with Exercise Capacity, Self-Efficacy, and Low-Moderate Physical Activity in Patients with Pulmonary Arterial Hypertension: A Randomized Controlled Study.

Background and Objectives: Pulmonary arterial hypertension (PAH) is a rare, chronic, progressive, and life-threatening disease; however, the appropriate target medical treatment today allows patients with PAH not only to survive but also to live a relatively normal life. However, patients face the challenge of adapting and maintaining a good quality of life, thus it is important to consider complex interventions related not only to medical treatment. Methods: This was a prospective, randomized, controlled, single-blind study. Twenty-one (21) patients diagnosed with PAH were included and randomly assigned to training or control group. All participants continued target medical therapy. Furthermore, TG underwent the individually tailored 12-week remote physiotherapy program. As a primary outcome measurement, the Impact on Participation and Autonomy Questionnaire (IPA) was used. Secondary outcome included aerobic capacity (6MWT), accelerometery and general self-efficacy (GSE). Data were collected at baseline, after 12 weeks and at follow-up 6 months after the beginning of the intervention. Results: A significant difference between the groups was found in the follow-up assessment on three of the four IPA subscales analyzed, AO, RF, and AI. The total IPA score decreased significantly in TG after the program, indicating an improved participation. In addition, in TG a significant increase in 6MWT results, daily time in low- or moderate-intensity physical activities, and GSE was observed. Conclusions: In summary, the individually tailored physiotherapy program investigated added to stable target medical therapy in patients with PAH encourages improvement and prevents possible deterioration of perceived participation of patients in activities of their everyday life in the context of one's health condition in the long term, along with improved exercise capacity and increased time spent in low- or moderate-intensity physical activities. Future studies are needed to develop and evaluate long-term intervention to support patients living with this rare, chronic, and life-threatening disease.

Patient perceptions of anticoagulant treatment with dabigatran or a vitamin K antagonist for stroke prevention in atrial fibrillation according to region and age: an exploratory analysis from the RE-SONANCE study.

BACKGROUND: The oral anticoagulant dabigatran offers an effective alternative to vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF), yet patient preference data are limited. The prospective observational RE-SONANCE study demonstrated that patients with AF, newly initiated on dabigatran, or switching to dabigatran from long-term VKA therapy, reported improved treatment convenience and satisfaction compared with VKA therapy. This pre-specified sub-study aimed to assess the impact of country and age on patients' perceptions of dabigatran or VKA therapy in AF. METHODS: RE-SONANCE was an observational, prospective, multi-national study (NCT02684981) that assessed treatment satisfaction and convenience in patients switching from VKAs to dabigatran (Cohort A), or newly diagnosed with AF receiving dabigatran or VKAs (Cohort B), using the PACT-Q questionnaire. Pre-specified exploratory outcomes: variation in PACT-Q2 scores by country and age (< 65, 65 to < 75, ≥ 75 years) (both cohorts); variation in PACT-Q1 responses at baseline by country and age (Cohort B). RESULTS: Patients from 12 countries (Europe/Israel) were enrolled in Cohort A (n = 4103) or B (n = 5369). In Cohort A, mean (standard deviation) PACT-Q2 score increase was highest in Romania (convenience: 29.6 [23.6]) and Hungary (satisfaction: 26.0 [21.4]) (p < 0.001). In Cohort B, mean (standard error) increase in PACT-Q2 scores between dabigatran and VKAs was highest in Romania (visit 3: 29.0 [1.3]; 24.5 [0.9], p < 0.001). Mean PACT-Q2 score increase by age (all p < 0.001) was similar across ages. PACT-Q1 responses revealed lowest expectations of treatment success in Romania and greatest concerns about payment in Estonia, Latvia, and Romania, but were similar across ages. CONCLUSIONS: Treatment satisfaction and convenience tended to favor dabigatran over VKAs. Regional differences in treatment expectations exist across Europe. TRIAL AND CLINICAL REGISTRY: Trial registration number: ClinicalTrials.gov NCT02684981. Trial registration date: February 18, 2016.

Protective Effects of Meldonium in Experimental Models of Cardiovascular Complications with a Potential Application in COVID-19.

Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID-19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID-19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension-induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hypertrophy and increased RVFAC by 50%. Mice with inflammation-induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID-19 patients.

Glomerular Filtration Rate as a Prognostic Factor for Long-Term Mortality after Acute Pulmonary Embolism.

BACKGROUND: In-hospital mortality for patients presenting with acute pulmonary embolism (PE) has been reported to be up to 7 times higher for patients with decreased estimated glomerular filtration rate (eGFR). However, few studies have assessed its effect on long-term mortality. OBJECTIVE: To determine the impact of eGFR and creatinine clearance (CrCl) on long-term all-cause mortality following acute PE in association with other routine laboratory analyses and comorbidities. PATIENTS/METHODS: The prospective study enrolled 141 consecutive patients presenting with objectively confirmed acute PE. Demographic, clinical data, comorbidities, and laboratory values were recorded. CrCl and GFR were estimated using the Cockcroft-Gault, MDRD, and chronic kidney disease (CKD)-EPI equations. Patients were followed up at 90 days and 1 year after the event. RESULTS: In univariate analyses, age, active cancer, PE severity index (PESI), CrCl and eGFR, D-dimer value, and high-density lipoprotein level were found to be significantly associated with mortality in 90 days and 1 year. Additionally, body mass index was significant in the 1-year follow-up. CrCl by Cockcroft-Gault (90-day: area under the curve [AUC] 0.763; 1-year: AUC 0.718) demonstrated higher discriminatory power for predicting mortality than eGFR by the MDRD (AUC 0.686; AUC 0.609) and CKD-EPI (AUC 0.697; AUC 0.630) equations. In multivariate analyses, active cancer, CrCl by Cockcroft-Gault (90-day: hazard ratio [HR] 0.948, 95% CI 0.919-0.979; 1-year: HR 0.967, 95% CI 0.943-0.991), eGFR by CKD-EPI (90-day: HR 0.948, 95% CI 0.915-0.983; 1-year: HR 0.971, 95% CI 0.945-0.998) were found to be independent predictors of mortality. eGFR by MDRD, D-dimer, and PESI value were significant prognostic factors for 90-day mortality. CONCLUSION: Decreased renal function is a prognostic factor for increased all-cause mortality 90 days and 1 year after acute PE.

Pulmonary Endarterectomy in Latvia: A National Experience.

Background and objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a hemodynamic state characterized by chronic obstruction in pulmonary circulation. The treatment of choice is pulmonary endarterectomy (PEA). The aim of our study was to compile and analyze the data of a small, national center, which has not yet been done in the Baltic states. Materials and methods: The data of Latvian CTEPH registry in timeframe from 1 September 2007 to 31 December 2016 was retrospectively analyzed and all patients who underwent PEA were included. Results: PEA was done for 7 patients. The in-hospital mortality was 14%. The 3-year survival rate was 86%. The procedure restored pulmonary blood pressure to normal values for three of the patients (42%). The remaining four patients (57%) had persistent pulmonary hypertension (mPAP > 30 mmHg), which required continuous therapy. There was a comparable decline in mean mPAP compared to baseline, 53.4 ± 14.4 mmHg to 44.3 ± 30 mmHg, respectively. At 12-month follow-up, there was a significant improvement in functional capacity, as seen by increased 6-min walk test distance and shifts in New York Heart Association functional class. Conclusions: Only 16% of all prevalent Latvian CTEPH patients have underwent PEA in the course of nine years, despite it being the treatment of choice for CTEPH. As PEA and other emerging treatment options, such as balloon pulmonary angioplasty, can only be done in expert centers, numerous organizational, logistical, and economic issues arise for patients of smaller countries, where such centers have not yet been created due to lack of experience and limited amount of patients.

Venous Thromboembolism Recurrence in Latvian Population: Single University Hospital Data.

Background and objectives: Recurrence of venous thromboembolism (VTE) after a primary event is common; however, no sufficient risk scores have been widely introduced in clinical practice. The aim of this study was to assess the risk factors for VTE recurrences, as well as the effect of treatment strategies on the recurrence rate in a single-center patient cohort. Materials and Methods: The prospective cohort study included consecutive patients in a single center from June 2014 till June 2018 presenting with acute VTE confirmed by imaging tests. All patients were followed up for at least one year or till death. Statistical analyses were conducted using IBM SPSS Statistics 23 and Stata 13. Competing risk of death was considered. Results: A total of 219 eligible patients were identified during the study period. Pulmonary embolism with or without deep vein thrombosis (DVT) was present in 95.9% (n = 210), isolated DVT was present in 4.1% (n = 9) of patients. The total number of documented recurrences was 13 (5.9%). Incidence rate was 5.6 per 100 person-years. Recurrent VTE predicted significantly higher mortality rate (hazard ratio (HR) 6.64 [95% CI 2.61-16.93]). In univariate analysis, active cancer was associated with higher recurrence rate (p = 0.036). In competing-risks regression model (with death as the competing risk), active cancer (subdistribution hazard ratio (SHR) 2.11 (95% CI 0.58-7.76)) did not retain statistical significance for VTE recurrence. Discontinuation and duration of anticoagulant treatment (≤6 or >6 months), and drug class in acute or long-term therapy (parenteral, vitamin K antagonist (VKA), direct oral anticoagulant (DOAC)) were not associated with recurrences (p > 0.05). Conclusions: Patients who experienced recurrent VTE had 6.6-fold higher mortality rate than patients with no recurrences. The presence of active cancer was not a statistically significant risk factor for recurrence when taking into account the competing risk of death. Duration and drug class of anticoagulation did not seem to impact recurrence rate.

Outcome during and after anticoagulant therapy in cancer patients with incidentally found pulmonary embolism.

Current guidelines suggest treating cancer patients with incidental pulmonary embolism comparably to patients with symptomatic pulmonary embolism.We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry to compare the rate of major bleeding and symptomatic pulmonary embolism during the course of anticoagulation and after its discontinuation in cancer patients with incidental pulmonary embolism.As of March 2016, 715 cancer patients with incidental pulmonary embolism had been enrolled in RIETE. During the course of anticoagulant therapy (mean 235 days), the rate of major bleeding was higher than the rate of symptomatic pulmonary embolism (10.1 (95% CI 7.48-13.4) versus 3.17 (95% CI 1.80-5.19) events per 100 patient-years, respectively), and the rate of fatal bleeding was higher than the rate of fatal pulmonary embolism (2.66 (95% CI 1.44-4.52) versus 0.66 (95% CI 0.17-1.81) deaths per 100 patient-years, respectively). After discontinuing anticoagulation (mean follow-up 117 days), the rate of major bleeding was lower than the rate of symptomatic pulmonary embolism (3.00 (95% CI 1.10-6.65) versus 8.37 (95% CI 4.76-13.7) events per 100 patient-years, respectively); however, there were no differences in the rate of fatal events at one death each.The risk/benefit ratio of anticoagulant therapy in cancer patients with incidental pulmonary embolism is uncertain and must be evaluated in further studies.

Age-Related Differences in the Presentation, Management, and Clinical Outcomes of 100,000 Patients With Venous Thromboembolism in the RIETE Registry.

INTRODUCTION: Although older adults represent a significant proportion of patients with venous thromboembolism (VTE), the data on the impact of age-related differences in the clinical presentation, management, and outcomes of VTE are scarce. METHODS: We analyzed data from the RIETE registry database, an ongoing global observational registry of patients with objectively confirmed VTE, to compare patient characteristics, clinical presentation, treatments, and outcomes between elderly (≥70 years) vs. non-elderly (<70 years) patients. RESULTS: From January 2001 to March 2021, 100,000 adult patients were enrolled in RIETE. Elderly patients (47.9%) were more frequently women (58.2% vs. 43.5%), more likely had unprovoked VTE (50.5% vs. 45.1%) and most often presented with severe renal failure (10.2% vs. 1.2%) and acute pulmonary embolism (PE) (vs. deep vein thrombosis) (54.3% vs. 44.5%) compared to non-elderly patients (p<0.001 for all comparisons). For the PE subgroup, elderly patients more frequently had non-low risk PE (78.9% vs. 50.7%; p<0.001), respiratory failure (33.9% vs. 21.8%; p<0.001) and myocardial injury (40.0% vs. 26.2%; p<0.001) compared to non-elderly patients. Thrombolysis (0.9% vs. 1.7%; p<0.001) and direct oral anticoagulants (8.8% vs. 11.8%; p<0.001) were less frequently administered to elderly patients. Elderly patients showed a significantly higher 30-day all-cause mortality (adjusted odds ratio [OR] 1.36, 95%CI: 1.22-1.52) and major bleeding (OR, 2.08; 95%CI, 1.85-2.33), but a lower risk of 30-day VTE recurrences (OR, 0.62, 95%CI, 0.54-0.71). CONCLUSIONS: Compared with non-elderly patients, elderly patients had a different VTE clinical profile. Advanced therapies were less frequently used in older patients. Age was an independent predictor of mortality.

Identification of Low-risk Patients With Acute Symptomatic Pulmonary Embolism.

BACKGROUND: Identification of patients with acute symptomatic pulmonary embolism (PE) who are at low-risk for short-term complications to warrant outpatient care lacks clarity. METHOD: In order to identify patients at low-risk for 30-day all-cause and PE-related mortality, we used a cohort of haemodynamically stable patients from the RIETE registry to compare the false-negative rate of four strategies: the simplified Pulmonary Embolism Severity Index (sPESI); a modified (i.e., heart rate cutoff of 100beats/min) sPESI; and a combination of the original and the modified sPESI with computed tomography (CT)-assessed right ventricle (RV)/left ventricle (LV) ratio. RESULTS: Overall, 137 of 3117 patients with acute PE (4.4%) died during the first month. Of these, 41 (1.3%) died from PE, and 96 (3.1%) died from other causes. The proportion of patients categorized as having low-risk was highest with the sPESI and lowest with the combination of a modified sPESI and CT-assessed RV/LV ratio (32.5% versus 16.5%; P<0.001). However, among patients identified as low-risk, the 30-day mortality rate was lowest with the combination of a modified sPESI and CT-assessed RV/LV ratio and highest with the sPESI (0.4% versus 1.0%; P=0.03). The 30-day PE-related mortality rates for patients designated as low-risk by the sPESI, the modified sPESI, and the combination of the original and modified sPESI with CT-assessed RV/LV ratio were 0.7%, 0.4%, 0.7%, and 0.2%, respectively. CONCLUSIONS: The combination of a negative modified sPESI with CT-assessed RV/LV ratio ≤1 identifies patients with acute PE who are at very low-risk for short-term mortality.

Venous thromboembolism characteristics, treatment and outcomes in young adults: findings from the Registro Informatizado de Enfermedad TromboEmbólica registry.

BACKGROUND: Venous thromboembolism (VTE) is rare in patients aged <21 years. Young adults aged 18 to 21 years are frequently included in adult VTE studies, whereas pediatric VTE studies include patients aged up to either 18 or 21 years. The clinical characteristics of young adult patients with VTE have not been well defined. OBJECTIVES: We aimed to highlight any unique characteristics or treatment considerations that may apply to young adult patients with VTE. METHODS: Data from the prospective, international Registro Informatizado de Enfermedad TromboEmbólica registry were used. Patients were stratified into subcohorts according to age. The clinical characteristics, risk factors, management, and outcomes of young adult patients with VTE were compared with those of adolescents aged 12 to 18 years and adults aged >21 years. RESULTS: Of 104 253 Registro Informatizado de Enfermedad TromboEmbólica patients enrolled until August 2022, 234 were adolescents and 884 were young adults. Less cases of pulmonary embolism were reported in adolescents (P < .001). Estrogen use was a common risk factor, more prevalent in adolescents and young adults (P < .001), whereas active cancer and immobilization were uncommon in both. Most patients were initially treated with low-molecular-weight heparin. VTE recurrence, major bleeding, and all-cause mortality rates were comparably low among adolescents and young adults. None of the patients aged <21 years died from VTE recurrence. CONCLUSION: Young adults have some distinctive VTE risk factors. While VTE presentation may be similar among young adults and older patients, the outcomes of patients aged <21 years are more favorable.

Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: A COMPERA analysis.

BACKGROUND: A diagnosis of idiopathic pulmonary arterial hypertension (IPAH) is frequently made in elderly patients who present with comorbidities, especially hypertension, coronary heart disease, diabetes mellitus, and obesity. It is unknown to what extent the presence of these comorbidities affects the response to PAH therapies and whether risk stratification predicts outcome in patients with comorbidities. METHODS: We assessed the database of COMPERA, a European pulmonary hypertension registry, to determine changes after initiation of PAH therapy in WHO functional class (FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) or N-terminal fragment of probrain natriuretic peptide (NT-pro-BNP), and mortality risk assessed by a 4-strata model in patients with IPAH and no comorbidities, 1-2 comorbidities and 3-4 comorbidities. RESULTS: The analysis was based on 1,120 IPAH patients (n = 208 [19%] without comorbidities, n = 641 [57%] with 1-2 comorbidities, and n = 271 [24%] with 3-4 comorbidities). Improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk from baseline to first follow-up were significantly larger in patients with no comorbidities than in patients with comorbidities, while they were not significantly different in patients with 1-2 and 3-4 comorbidities. The 4-strata risk tool predicted survival in patients without comorbidities as well as in patients with 1-2 or 3-4 comorbidities. CONCLUSIONS: Our data suggest that patients with IPAH and comorbidities benefit from PAH medication with improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk, albeit to a lesser extent than patients without comorbidities. The 4-strata risk tool predicted outcome in patients with IPAH irrespective of the presence of comorbidities.