Temporal Trends in Diagnostic Hemodynamics and Survival of Patients with Pulmonary Hypertension: A Single-Center Study.

Advances in the diagnosis and treatment of pulmonary hypertension (PH) have gradually improved the disease course. This retrospective cohort study aims to explore the diagnostic hemodynamic profile and survival of PH patients and their temporal changes, as well as investigate potential prognostic factors. Overall, 257 adult patients were diagnosed with PH following right heart catheterization (RHC) from January 2008 to June 2023 according to the hemodynamic cut-off values proposed by the corresponding ESC/ERS guidelines at the time RHC was performed. Of these patients, 46.3% were Group 1, 17.8% Group 2, 14.0% Group 3, 18.0% Group 4, and 3.0% Group 5 PH. Temporal improvement in both diagnostic hemodynamic profile and survival of patients with PH and pulmonary arterial hypertension (PAH) was identified after 2013. Survival analysis demonstrated 5-year survival rates of 65% in Group 1 PH (90.3% in idiopathic PAH) and 77% in Group 4 PH. PAH patients being at low risk at diagnosis presented a similar 1-year all-cause mortality rate (12.4%) with high-risk ones (12.8%), primarily due to non-PH-related causes of death (62%), while high-risk patients died mostly due to PH (67%). The observed improvements in diagnostic hemodynamic profiles and overall survival highlight the importance of timely diagnosis and successful treatment strategies in PH.

Right Ventricular Myocardial Work Characterization in Patients With Pulmonary Hypertension and Relation to Invasive Hemodynamic Parameters and Outcomes.

Noninvasive evaluation of indexes of right ventricular (RV) myocardial work (RVMW) derived from RV pressure-strain loops may provide novel insights into RV function in precapillary pulmonary hypertension. This study was designed to evaluate the association between the indexes of RVMW and invasive parameters of right heart catheterization and all-cause mortality. Noninvasive analysis of RVMW was completed in 51 patients (mean age 58.1 ± 12.7 years, 31% men) with group I or group IV pulmonary hypertension. RV global work index (RVGWI), RV global constructive work (RVGCW), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were compared with parameters derived invasively during right heart catheterization. Patients were followed-up for the occurrence of all-cause death. The median RVGWI, RVGCW, RVGWW, and RVGWE were 620 mm Hg%, 830 mm Hg%, 105 mm Hg% and 87%, respectively. Compared with conventional echocardiographic parameters of RV systolic function, RVGCW and RVGWI correlated more closely with invasively derived RV stroke work index (R = 0.63, p <0.001 and R = 0.60, p <0.001, respectively). Invasively derived pulmonary vascular resistance correlated with RVGWW (R = 0.63, p <0.001), RVGWE (R = 0.48, p <0.001), and RV global longitudinal strain (R = 0.58, p <0.001). RVGCW (hazard ratio 1.42 per 100 mm Hg% <900 mm Hg%, 95% confidence interval 1.12 to 1.81, p = 0.004) and RVGWI (hazard ratio 1.46 per 100 mm Hg% <650 mm Hg%, 95% confidence interval 1.09 to 1.94, p = 0.010) were significantly associated with all-cause mortality, whereas RV global longitudinal strain, RVGWE, and RVGWW were not. In conclusion, indexes of RVMW were more closely correlated with invasively derived RV stroke work index and peripheral vascular resistance than conventional echocardiographic parameters of RV systolic function. Decreased values of RVGCW and RVGWI were associated with all-cause mortality, whereas conventional echocardiographic parameters of RV function were not.

Balloon Pulmonary Angioplasty in Patients with Chronic Thromboembolic Pulmonary Hypertension in Greece: Data from the Hellenic Pulmonary Hypertension Registry.

Balloon pulmonary angioplasty (BPA) is a novel and promising treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA) and for those with persistent or recurrent pulmonary hypertension after PEA. We present the results of BPA procedures in CTEPH patients included in the Greek Pulmonary Hypertension Registry, evaluating the real-life efficacy and safety. We analyzed data from 180 BPA procedures (2−17/patient, mean 8 ± 4/patient, 1248 dilated vessels, 0−18/session). Significant improvements were observed in mean pulmonary arterial pressure (a reduction by 44%, p < 0.001), pulmonary vascular resistance (reduction by 60%, p < 0.001), and NT-proBNP (decrease by >70%, p: 0.003), while cardiac index improved modestly (9% increase, p = 0.143). We had 37 BPA-related non-fatal complications (20.6% in all interventions), predominantly including hemoptysis. Overall survival was 91%, 75% and 62% at 3, 4 and 5 years, respectively. Therefore, BPA may be a promising therapeutic option in patients with CTEPH in Greece.

Epidemiology and Management of Chronic Thromboembolic Pulmonary Hypertension in Greece. Real-World Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m2, respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment; specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients (p < 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients (p = 0.33).

Peripheral microangiopathy in Eisenmenger syndrome: A nailfold video capillaroscopy study.

BACKGROUND: Eisenmenger syndrome (ES) comprises a severe phenotype of pulmonary arterial hypertension characterized by angiopathy of the lung circulation. The aim of the present study was to demonstrate the presence of systemic microvascular abnormalities in patients with ES using nailfold video-capillaroscopy (NVC) and to identify potential correlations of nailfold capillaroscopic characteristics with non-invasive markers of systemic organ function. METHODS: Α cross-sectional NVC study was performed in 17 consecutive patients with ES and 17 healthy controls matched for age and sex. NVC quantitative (capillary density, capillary dimensions, haemorrhages, thrombi, shape abnormalities) and qualitative (normal, non-specific or scleroderma pattern) parameters were evaluated. RESULTS: Patients with ES [median age 40 (18-65) years, 11 women] presented reduced capillary density [8.8 (7.2-10.2) loops/mm vs. 9.9 (8.3-10.9) loops/mm, p = .004] and increased loop width [15.9 (10.3-21.7) µm vs. 12.3 (7.6-15.2) µm, p < .001], while they had significantly more abnormal capillaries than healthy controls [2.5 (0.9-5.4) abnormal loops/mm vs. 1.0 (0.0-1.7) abnormal loops/mm, p < .001]. NVC shape abnormalities in ES were positively correlated with NT-proBNP (r = 0.52, p = .03) and were negatively associated with estimated glomerular filtration rate (r = -0.60, p = .02). Additionally, capillary loop diameter was positively correlated with increased haemoglobin levels (r = 0.55, p = .03) and negatively correlated with reduced peripheral oxygen saturation (r = - 0.56, p = .02). CONCLUSIONS: This study supports the hypothesis of peripheral microvascular involvement in ES parallel to pulmonary microangiopathy detected by NVC. Further longitudinal studies are needed to confirm our preliminary results.

Peripheral microangiopathy in precapillary pulmonary hypertension: a nailfold video capillaroscopy prospective study.

BACKGROUND: Although pulmonary vascular bed has been the main subject of research for many years in pulmonary hypertension (PH), interest has recently started to divert towards the possibility of a co-existing peripheral microangiopathy. The aim of the current study was to investigate the presence of nailfold video-capillaroscopic (NVC) structural changes in patients with precapillary PH and to identify possible associations of NVC measurements with markers of disease severity. METHODS: Α prospective case-control study was performed in 28 consecutive patients with precapillary PH [14 with idiopathic pulmonary arterial hypertension (IPAH) and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)] and 30 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability capillaroscopic images were reviewed by two independent investigators. For multiple comparisons among continuous variables, one-way ANOVA or the Kruskal-Wallis test were used. Differences between the groups were tested with post-hoc analysis with adjustment for multiple comparisons (Bonferroni test). RESULTS: Both IPAH (71.4% were women, mean age 53.1 ± 13.4 years) and CTEPH (64.3% women, mean age 60.9 ± 14.4 years) groups presented reduced capillary density compared to healthy controls (8.4 ± 1.2 loops/mm and 8.0 ± 1.2 loops/mm vs. 9.7 ± 0.81 loops/mm, p < 0.001) and increased loop width (15.7 ± 3.9 µm and 15.8 ± 1.9 µm vs. 11.5 ± 2.3 µm, p < 0.001). More than half of patients with IPAH presented microhaemorrhages on capillary nailfold, while increased shape abnormalities in capillary morphology and more capillary thrombi per linear mm were detected in patients with CTEPH compared to patients with IPAH and healthy controls. All PH patients presented a non-specific NVC pattern compared to controls (p < 0.001). CONCLUSION: The findings of the study reveal a degree of significant peripheral microvascular alterations in patients with IPAH and CTEPH, suggesting a generalized impairment of peripheral microvasculature in pulmonary vascular disease.

Transition protocol from subcutaneous treprostinil to intravenous epoprostenol in deteriorating patients with pulmonary arterial hypertension.

BACKGROUND: Despite advantages in the treatment options of pulmonary arterial hypertension, continuous parenteral prostanoid administration, although often complicated by serious side effects, remains the treatment of choice for patients with advanced disease. The need of transitioning from one parenteral prostanoid agent to the other is often faced in the daily clinical practise. Up to today, there is no established transition protocol from subcutaneous treprostinil to intravenous epoprostenol. METHODS: A staggered approach to subcutaneous treprostinil down-titration with simultaneous epoprostenol up-titration is described. Subcutaneous treprostinil is down-titrated by 5 ng/kg/min every 5 h while intravenous epoprostenol is up-titrated by 2 ng/kg/min every 2 h. RESULTS: The designed protocol was implemented in 4 patients with pulmonary arterial hypertension (3 women, median age 70.5 (range 38-79) years). Median starting subcutaneous treprostinil dose was 44.5 (range 37-100) ng/kg/min and median treprostinil down-titration time was 32.5 (range 25-85) hours. The median maximal epoprostenol dose was 36 (range 28-90) ng/kg/min, achieved in 36 (range 30-90) hours. Only mild prostanoid-related side effects were reported. CONCLUSIONS: The proposed staggered transition protocol from subcutaneous treprostinil to intravenous epoprostenol was safe in a limited number of patients with pulmonary arterial hypertension.

Quality of Life is Related to Haemodynamics in Precapillary Pulmonary Hypertension.

BACKGROUND: Precapillary pulmonary hypertension (PH) is characterised by compromised functional capacity and impaired quality of life. Assessment of haemodynamics is routinely used for initial diagnosis, follow-up, and risk stratification in these patients. The purpose of this study was to investigate the relation of health-related quality of life (HRQoL) as assessed by emPHasis-10 score, a self-assessment questionnaire assessing breathlessness, fatigue, control, and confidence, to haemodynamic and neurohormonal indices in patients with precapillary PH. METHOD: This was a prospective cross-sectional study which included stable patients with precapillary PH. All patients underwent right heart catheterisation, 6-minute walk test, N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement, and assessment of HRQoL with the emPHasis-10 scale. RESULTS: Overall, 54 patients were included (32 women; mean age, 58.4 ± 14.6 yr). Mean emPHasis-10 score was 19.2 ± 12.0. EmPHasis-10 score correlated with World Health Organization functional class (r = 0.52, p < 0.001), 6-minute walk distance (r=-0.56, p < 0.001), and log10(NT-proBNP) (r = 0.41, p < 0.01). A positive correlation of emPHasis-10 score with mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) and a negative correlation with mixed venous oxygen saturation and cardiac index was observed, after adjustment for age, sex, body mass index, and PH group. In a subgroup analysis of patients with pulmonary arterial hypertension (n = 34) there was a stronger correlation of emPHasis-10 score with mPAP (r = 0.86, p < 0.001) and PVR (r = 0.69, p < 0.01), but no correlation with cardiac index and mixed venous oxygen saturation. CONCLUSIONS: Self-assessment of quality of life with the use of the emPHasis-10 score reflects functional capacity and is correlated with haemodynamic and neurohormonal indices of right heart dysfunction in patients with precapillary PH.

Epidemiology and initial management of pulmonary arterial hypertension: real-world data from the Hellenic pulmOnary hyPertension rEgistry (HOPE).

Pulmonary arterial hypertension (PAH) is a heterogenous clinical entity with poor prognosis, despite recent major pharmacological advances. To increase awareness about the pathophysiology, epidemiology, and management of the disease, large national registries are required. The Hellenic pulmOnary hyPertension rEgistry (HOPE) was launched in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. Baseline epidemiologic, diagnostic, and initial treatment data of consecutive patients with PAH are presented in this article. In total, 231 patients with PAH were enrolled from January 2015 until April 2018. At baseline, about half of patients with PAH were in World Health Organization functional class II. The majority of patients with PAH (56.7%) were at intermediate 1-year mortality risk, while more than one-third were low-risk patients, according to an abbreviated risk stratification score. Half of patients with PAH were on monotherapy, 38.9% received combination therapy, while prostanoids were used only in 12.1% of patients. In conclusion, baseline data of the Greek PAH population share common characteristics, but also have some differences with other registries, the most prominent being a better functional capacity. This may reflect earlier diagnosis of PAH that in conjunction with the increased proportion of patients with atypical PAH could partially explain the preference for monotherapy and the limited use of prostanoids in Greece. Nevertheless, early, advanced specific therapy is strongly recommended.

Right Atrial Function Predicts Clinical Outcome in Patients with Precapillary Pulmonary Hypertension.

BACKGROUND: Although the primary role of right atrial (RA) size in the diagnosis and risk stratification of precapillary pulmonary hypertension (PH) has been studied, little is known about the clinical significance of RA function. In line with studies assessing left atrial function in heart failure, the aim of this study was to introduce the RA function index (RAFi) and to explore its prognostic power in precapillary PH. METHODS: RA emptying fraction was calculated as (RA end-systolic volume - RA end-diastolic volume) × 100/(RA end-systolic volume). RAFi was calculated as (RA emptying fraction × right ventricular outflow tract velocity-time integral)/(RA end-systolic volume index). Patients were followed for the end point of clinical failure, which was defined as death, hospitalization because of PH, or disease progression. RESULTS: In total, 47 patients with precapillary PH were included. Mean RAFi was 16.1 ± 22.3%. Over a median follow-up period of 25 months (interquartile range, 9.5-41.1 months), 29 patients experienced clinical failure. Univariate Cox proportional-hazard analysis showed that RAFi was a predictor of clinical failure (hazard ratio, 0.935; 95% CI, 0.890-0.981; P = .007). Addition of RAFi to established predictors of outcomes, including 6-minute walk distance, N-terminal pro-B-type natriuretic peptide, and RA area, improved their prognostic power. CONCLUSIONS: RAFi is an easily assessed echocardiographic parameter, which is strongly predictive of clinical outcomes in patients with precapillary PH. Further studies are needed to validate RAFi and define its role in clinical practice.