Arterial Hypertension Patients Research Articles

Abstract 13266: Sex Specific Differences in the Gut Microbiome in Patients With Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PAH) patients exhibit sexual dimorphism in pulmonary vascular remodeling and right ventricular (RV) dysfunction. While female PAH patients have severe pulmonary vascular remodeling, male PAH patients have worse RV function. Inflammation, a key component of PAH pathobiology, has been implicated as a potential mechanism for sexual dimorphism. Gut dysbiosis causes systemic inflammation. However, it is unknown whether gut dysbiosis contributes to sexual dimorphism in PAH. Hypothesis: There are sex-specific differences in the gut microbiome and microbial metabolites of PAH patients. Methods: 16S ribosomal ribonucleic acid gene sequencing was performed on stool samples from PAH patients (n=73). Markers of inflammation and circulating microbial metabolites were measured using plasma samples. Results: There was no significant difference in the Shannon diversity indices or species richness (Chao1 indices) between the gut microbiomes of male and female PAH patients. Moreover, principal component analysis of pairwise Bray-Curtis dissimilarity indices revealed no distinct microbiome compositions dependent on sex. There was no difference in serum claudin-3, a marker of gut permeability, and serum interleukin 6 levels between male and female PAH patients. When examining microbial metabolites, including trimethylamine N-oxide, short chain fatty acids, and secondary bile acids, no sex-specific differences were observed. Linear discriminant analysis of effect size revealed that there were no taxonomic differences based on sex. Conclusions: Male and female PAH patients do not possess distinct differences in their gut microbiomes or metabolites. There are also no sex-specific taxonomic differences. These findings do not support our hypothesis that gut dysbiosis may serve as a possible explanation for the sexual dimorphism observed in PAH.

Abstract 9453: The Role of Repeated PET/MRI Hybrid Imaging in Pulmonary Arterial Hypertension Patients Receiving Specific Therapy, Four-Year Observation

Introduction: PET/MRI hybrid imaging in pulmonary arterial hypertension (PAH) provides new prognostic parameters, which identify the group of patients who potentially might benefit from early PAH therapy escalation. In previous study we confirmed that right ventricle (RV) metabolic alterations are linked with PAH hemodynamics and both precede clinical deterioration. Hypothesis: Repeating PET/MRI scans improves PAH patients’ management. Methods: Twenty stable patients (49.9±14.9 y.o.) had second simultaneous PET/MRI scans during follow up visit (FU) after 24 months from baseline scans. SUV RV /SUV LV ratio was used to estimate and compare cardiac glucose uptake before and after PAH therapy escalation. Next, observation was extended to 48 months in total. Results: Between baseline and FU visits, 16 patients needed therapy escalation (mostly to prostacyclin); median SUV RV /SUV LV (observed in PET) has lowered with improvement in both RV ejection fraction (MRI) and mean pulmonary artery pressure (catheterization). In long observation (48 months) mean time to clinical worsening was 25.2±17.1 months. Cut-off value of PET-derived SUV RV /SUV LV in ROC analysis was 0.54, suggesting that even subtle shift in cardiac glucose metabolism in PAH may result in worse prognosis. PAH patients with baseline SUV RV /SUV LV higher than 0.54 had significantly worse prognosis in the 48-months observation (log-rank test, p=0.003). Finally, patients with follow-up SUV RV /SUV LV ratio higher than 1.14 had still significantly worse prognosis despite of previously escalated treatment during FU visits (log-rank test, p=0.04, Figure). Conclusions: Repeated PET/MRI imaging provides non-invasive assessment of PAH patients’ hemodynamics, prognosis and helps to determine effectiveness of targeted therapy affecting subtle cardiac metabolic changes. Even single PET/MRI assessment in PAH patients may help to determine long-term prognosis and to plan appropriate PAH therapy.

Features of vascular rigidity in patients with arterial hypertension in combination with chronic heart failure and senile asthenia syndrome

Objective. The aim of the study was to evaluate the features of vascular rigidity in patients with arterial hypertension (AH) depending on the presence of chronic heart failure (CHF) and senile asthenia syndrome (SAS).Design and methods. 320 patients with AH were divided into two main groups: group 1 — patients with AH and CHF (n = 161), group 2 — patients with AH without CHF (n = 159). Depending on the presence of SAS, patients of each group were divided as follows: subgroup 1A — patients with AH, CHF and SAS (n = 84), subgroup 1B — patients with AH, CHF without SAS (n = 77), subgroup 2A — patients with AH, SAS without CHF (n = 84), subgroup 2B — patients with AH without CHF and without SAS (n = 75). To identify SAS, we used the “Age is not a barrier” questionnaire and a short battery of physical functioning tests. The parameters of vascular stiffness were determined using a device for daily monitoring of blood pressure BPLab using Vasotens technology (Peter Telegin, Nizhny Novgorod). The obtained data were processed using STATISTICA 12.0 (StatSoft Inc., USA), SPSS 21.0, MedCalc (version 9.3.5.0).Results. Analysis of the effect of SAS on vascular stiffness showed that in patients with AH, CHF and SAS, compared with patients with AH, CHF without SAS, there were statistically significantly lower values of the reflected wave propagation time (RWTT) (p = 0,001) against the background of higher values pulse wave velocity in the aorta (РWVао) (p < 0,001), arterial stiffness index (ASI) (p = 0,0001) and ambulatory arterial stiffness index (AASI) (p = 0,002), which indicates more pronounced vascular stiffness in patients with AH, CHF in the presence of SAS. In the group of patients with AH and SAS without CHF, compared with patients with AH without CHF and without SAS, higher values of РWVао (p < 0,001) and “adjusted” index of augmentation index (AIх@75) (p < 0,001) were revealed, which allows to judge the effect of SAS on the development of arterial stiffness in patients with AH without CHF. Analysis of the effect of CHF on vascular stiffness showed that in patients with AH, SAS and CHF, compared with patients with AH, SAS without CHF, statistically significantly lower values of RWTT (p < 0,001) and higher values of РWVао (p = 0,024) were noted, ASI (p < 0,001), AASI (p < 0,001), maximum rate of blood pressure rise (dP/dtmax) (p < 0,001) and AIх@75 (p < 0,001). In the group of patients with AH, CHF without SAS, compared with patients with AH without CHF and without SAS, lower values of RWTT (p < 0,001) and higher values of РWVаo (p = 0,004), ASI (p < 0,001), AASI (p < 0,001) and dP/dtmax (p < 0,001), which in turn demonstrates the contribution of CHF to the development of vascular stiffness in AH patients without SAS. CS.Conclusions. In hypertensive patients over 80 years of age, the development of both SAS and CHF was accompanied by limited compliance of the aortic walls and increased vascular stiffness in the peripheral arteries. Significantly more pronounced changes in vascular stiffness parameters were noted in patients with a combination of AH, CHF and SAS compared with those in patients with AH and CHF or AH and SAS, which indicates an increase in vascular stiffness, and, consequently, a higher risk of cardiovascular diseases in this combined pathology.

Clinical differences between children and adults with idiopathic and heritable pulmonary arterial hypertension.

Although previous studies have demonstrated that paediatric pulmonary arterial hypertension remains distinct from that in adults, there are limited studies evaluating a direct comparison between children and adults. The aim of this head-to-head comparison study was to compare the gender, haemodynamic parameters, and prognosis between paediatric and adult pulmonary arterial hypertension. We retrospectively assessed the clinical differences in 40 childhood-onset (under 20 years old) patients and 40 adult-onset patients with idiopathic and heritable pulmonary arterial hypertension who were followed up at two centres. There was no female predominance among patients with childhood-onset pulmonary arterial hypertension (child female: 42.5%, adult female: 80%). The percent of New York Heart Association functional class IV in adult-onset pulmonary arterial hypertension tended to be higher than those in childhood-onset pulmonary arterial hypertension (22.5 and 10%, respectively), although children had worse haemodynamic parameters at diagnosis (mean pulmonary artery pressure (children versus adults); median 65 mmHg versus 49 mmHg, p < 0.001). There was no significant difference in the event-free survival rate between the two groups (95% vs. 85%) during the follow-up period (median, 96 months; range, 1-120 months). Although paediatric pulmonary arterial hypertension patients had worse haemodynamic parameters at diagnosis than adults, children survived as long as adults with appropriate therapeutic strategies.

Features of the manifestation of arterial hypertension in patients with a new coronavirus infection

The purpose. Assessment of the presence of the cardiovascular risk factors, associated clinical conditions, the degree of target organ damage in patients with arterial hypertension depending on the new coronavirus infection. Material and methods. In a retrospective cohort study 284 patients with arterial hypertension were identified, 162 of them had a novel coronavirus infection and 122 patients didn’t have a history of a new coronavirus infection. Patients who had a new coronavirus infection were divided into groups depending on the disease. Inclusion criteria were the presence of arterial hypertension in history and taking antihypertensive therapy. Results. Patients with hypertension who’ve had a new coronavirus infection are more likely to have risk factors such as smoking, overweight, early menopause as opposed to patients with hypertension without indication of past COVID-19. Comparing patients with increased severity of the novel coronavirus infection elevated uric acid levels and hypercholesterolemia were associated with more severe COVID-19 (p &lt; 0.05). Patients with chronic kidney disease, cerebrovascular disease, detection of atherosclerotic lesions of the brachiocephalic arteries and diabetes mellitus have an increased probability of deaths occur from the novel coronavirus infection (p &lt; 0.05). There was no significant difference between the compared groups of coronary heart disease, atrial fibrillation, chronic heart failure and also the daily blood pressure profile and a severe course of COVID-19. Сonclusion. The presence of diabetes mellitus, cerebrovascular disease, chronic kidney disease, detection of atherosclerotic lesions of the brachiocephalic arteries, and also hyperuricemia or hypercholesterolemia in patients with hypertension revealed a risk of severe coronavirus infection.

Characteristic of the uncontrolled hypertension course in patients of the aral sea region with uncomplicated hypertensive crisis

Abstract Purpose To study the features of the course of uncontrolled arterial hypertension (AH) in the Aral Sea region with the identification of the prevalence of various genotypes of the angiotensinogen (AGT) gene in patients with uncomplicated hypertensive crisis. Methods The genetic part included 94 patients with uncomplicated hypertensive crisis, an average age of 55.3±8.6 years, 54 (58.3%)women and 40 men (41.7%). The control group consisted of 50 healthy women and men, an average age of 52.7±6.4 years in equal proportion. The genetic study was carried out by real-time PCR with the determination of the prevalence of genotypes and alleles of genetic polymorphisms AGT 521 C&amp;gt;T, AGT 704 T&amp;gt;C. Results Patients with uncomplicated hypertensive crisis were characterized by LV hypertrophy, thickening of the intima-media thickness of the common carotid artery, and kidney damage. Henken's test showed that patients with AH require a significantly higher concentration of table salt to determine the threshold of taste sensitivity than in the control group: 0.51±0.17% versus 0.21±0.14% concentration of NaCl. The distribution of 704T&amp;gt;C genotypes of the AGT gene polymorphism was as follows: CC genotype 43.6%, CT genotype 45.8%, TT genotype 10.6% of cases, χ2=32.777, p=0.000; C allele – 66.5%, T allele - 33.5% of cases, χ2=40.894, p=0.000. Among healthy individuals, the distribution by genotypes showed a significant predominance of the CC genotype: CC 76%, CT 24%, TT genotype was not detected in the presented sample, χ2=67.92, p=0.000; C-allele 88%, T-allele 12%, χ2=115.52, p=0.000. The above data of the group of patients and healthy people corresponded to the theoretical Hardy-Weinberg equilibrium. The distribution of 521T&amp;gt;C genotypes of the AGT gene polymorphism among AH patients was as follows: CC genotype – 79.8%, CT genotype – 16%, TT genotype – 4.2% of cases, χ2=139.8, p=0.000; C-allele – 87.8%, T-allele – 12.2%, χ2=214.5, p=0.000. Among healthy individuals, a significant predominance of the CT genotype was shown: CC genotype – 40%, CT genotype – 60% of cases, χ2=42.0, p=0.000; C-allele – 70%, T-allele – 30%, χ2=32.0, p=0.000. The above data of the group of patients and healthy people did not correspond to the theoretical Hardy-Weinberg equilibrium Conclusion Patients with uncomplicated hypertensive crisis, living in the aral sea region, are characterized by severe damage of target organs, a high threshold of taste sensitivity to table salt. Based on genetic models of inheritance, a significant prevalence of the C-allele and CC genotype 704 T&amp;gt;C AGT gene polymorphism in healthy individuals was revealed, which characterizes the C-allele and CC genotype as protective against AH in people of the Aral Sea region. Significantly greater accumulation of the C-allele 521 C&amp;gt;T polymorphism of the AGT gene among AH patients is a factor of predisposition to a complicated course of AH in people of the aral sea region. Funding Acknowledgement Type of funding sources: None.

Characterisation of pulmonary arterial hypertension patients with cardiovascular comorbidities treated with selexipag: real-world evidence from the EXPOSURE study

Abstract Background A recent post-hoc analysis of the GRIPHON randomised controlled trial [1] showed that selexipag reduces the risk of a morbidity/mortality event versus placebo in pulmonary arterial hypertension (PAH) patients, irrespective of comorbidity burden. Real-world evidence is needed on the management of PAH patients with cardiovascular comorbidities receiving selexipag. Purpose To describe characteristics, treatment patterns and outcomes of PAH patients with cardiovascular comorbidities receiving selexipag in the real world. Methods EXPOSURE is an ongoing, multicentre, prospective, observational study of PAH patients initiating a PAH-specific therapy in Europe and Canada. Patients initiating selexipag were grouped by number of cardiovascular comorbidities present prior to or at therapy initiation: BMI ≥30 kg/m2, systemic hypertension, diabetes mellitus, and coronary artery disease. Results As of November 2020, 382 selexipag-treated patients had follow-up and comorbidity data available: 44% (n=169) had 0, 30% (n=114) had 1, 18% (n=70) had 2, and 8% (n=29) had ≥3 comorbidities. At selexipag initiation, patients with comorbidities were older, more likely to have idiopathic/heritable PAH and had worse functional capacity (lower median 6-minute walk distance, higher proportion in WHO functional class III/IV) vs those without comorbidities (Table 1). Overall, haemodynamic parameters were similar across groups (Table 1). Patients with a higher comorbidity burden were more likely to be at high-risk of 1-year mortality (COMPERA method) vs those with a lower comorbidity burden (Table 1). Patients predominantly initiated selexipag as part of triple combination therapy (mainly in addition to an endothelin receptor antagonist and phosphodiesterase type 5 inhibitor), regardless of comorbidity burden (76–79% across groups). The duration of exposure and the median selexipag maintenance dose were similar across groups (Table 2). The proportion of patients hospitalised and the proportion who discontinued selexipag during the exposure period are shown in Table 2. 5% (n=8) of patients in the 0 comorbidities group, 12% (n=14) in the 1 comorbidity group, 0% in the 2 comorbidities group, and 10% (n=3) in the ≥3 comorbidities group died during the exposure period. Conclusions These real-world data from Europe and Canada suggest that more than 50% of patients who initiated selexipag had ≥1 cardiovascular comorbidity. Patients with comorbidities had more severe functional impairment vs those without. Overall haemodynamic profiles reflected Group 1 Pulmonary Hypertension and were similar across groups. Selexipag was initiated predominantly as part of triple combination therapy in all groups and most patients remained on selexipag, regardless of comorbidity burden. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson &amp; Johnson

Concomitant initiation of combination therapy with macitentan and tadalafil in pulmonary arterial hypertension (PAH) patients with comorbidities: real-world data from OPUS and OrPHeUS

Abstract Background Guidelines for the management of pulmonary arterial hypertension (PAH) recommend early combination therapy of an endothelial receptor antagonist (ERA) and a phosphodiesterase type-5 inhibitor (PDE5i) [1]. There is, however, limited guidance about the management of PAH patients with comorbidities. Purpose To describe the demographics, clinical characteristics, safety, tolerability, and outcomes associated with initiation of the ERA macitentan and the PDE5i tadalafil in patients with comorbidities in the US OPsumit® USers (OPUS) and the OPsumit® Historical USers cohort (OrPHeUS) combined dataset. Methods This analysis reports data from the OPUS registry (Apr 2014–Jun 2020) and OrPHeUS medical chart review (Oct 2013–Mar 2017) on PAH patients initiating macitentan and tadalafil (M+T) combination therapy, in any order, as concomitant initiation (≤60 days apart, concomitant initiation group). The index date was defined as the start date of the second therapy (i.e., the start of combination therapy). Patients were further grouped by the number of comorbidities present prior to or at macitentan initiation: systemic hypertension, diabetes, renal insufficiency, BMI ≥30 kg/m2, other signs of right heart failure and atrial fibrillation. Results are presented descriptively alongside results for all PAH patients receiving M+T combination therapy (overall M+T group). Results Of the 1336 PAH patients that received M+T combination therapy, 431 (32%) were in the concomitant initiation group. In the concomitant initiation and overall M+T groups, respectively: 72% and 68% had ≥1 comorbidity, and the most common were systemic hypertension (47% and 47%), obesity (32% and 26%) and diabetes (23% and 22%). Patients were more likely to be older, male and have idiopathic/heritable PAH with increasing comorbidity burden (Table 1). Patients in the concomitant initiation group were more likely to be incident (median time from diagnosis: 1–2 months vs 9–24 months in the overall M+T group; Table 1). Most patients had ≥1 adverse event (AE); in both groups, patients with a high comorbidity burden (≥3) were more likely to have had an AE and to have discontinued treatment (Table 2). The incidence rate of first all-cause hospitalisation and mortality by comorbidity was comparable between the concomitant initiation and overall M+T groups. Conclusions In the real-world, concomitant initiation of M+T is used in PAH patients with comorbidities, usually shortly after diagnosis. Patient characteristics were similar for the concomitant initiation and overall M+T groups, with the exception of time from diagnosis. At index date, age, gender proportion, and PAH aetiology differed between the comorbidity groups. The safety profile of M+T combination therapy in the concomitant initiation group was consistent with that in the overall M+T group. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson &amp; Johnson

Peripheral microvascular function is linked to cardiac involvement on CMR in systemic sclerosis-related pulmonary arterial hypertension patients

Abstract Background Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation and fibrosis, and carries one of the worst prognosis in patients who also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, SSc-PAH patients demonstrate disproportionately high morbidity and mortality, presumably due to cardiac involvement. Purpose To determine the pathophysiology of cardiac involvement in SSc, cardiovascular magnetic resonance (CMR) measures of perfusion, inflammation and fibrosis were compared between SSc-PAH and idiopathic PAH (IPAH) patients. In addition, the correlation between myocardial involvement on CMR and known markers of peripheral microvascular function was assessed. Methods Consecutive patients with SSc-PAH and IPAH of similar age and gender, consecutively underwent CMR imaging, and nailfold capillaroscopy (NC) with post-occlusive reactivity hyperaemia-test (PORH-test). CMR imaging included T2 mapping (inflammation), pre- and postcontrast T1 mapping to calculate the extracellular volume fraction (ECV, fibrosis), and adenosine-stress perfusion imaging to measure the relative myocardial upslope (microvascular perfusion), all measurements were performed on the left ventricle. These CMR markers were related to peripheral microvascular function by NC and PORH-test. Results Twenty SSc-PAH patients (71 [62–77] years, 14% male) and 5 IPAH patients (69 [47–77] years, 20% male) were included. SSc-PAH patients had higher ECV and T2 values than IPAH patients. NC showed lower average capillary density and reduced recruitment of capillaries after PORH in SSc-PAH patients, corresponding to impaired microvascular structure and function. Both higher ECV and T2 values correlated with lower average capillary density (r=−0.454 and −0.583, respectively, p&amp;lt;0.05 for both). Additionally, higher T2 values and lower relative myocardial upslope correlated with worse peripheral microvascular function measured by PORH-test (r=−0.471 and r=0.421, respectively, p&amp;lt;0.05 for both). Conclusion SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared to IPAH patients. These markers correlated well with worse peripheral microvascular function, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may have important therapeutic implications, for which future studies are warranted evaluating the role of anti-inflammatory/anti-fibrotic therapy. Funding Acknowledgement Type of funding sources: None.

Added prognostic value of cardiopulmonary test variables in low-risk pulmonary artery hypertension patients

Abstract Background Pulmonary artery hypertension (PAH) results in progressive right heart failure, functional decline and finally death or the need for a lung transplant. Prognostic assessment based on a 6-minutes walking test (6MWT) may be insufficient due to the possibility of a ceiling effect, especially in young patients. Purpose To demonstrate the added prognostic value of functional assessment by cardiopulmonary exercise testing (CPET) in patients with a low-risk 6MWT. Methods We conducted a retrospective cohort study in patients with PAH referred to two centres between June 2006 and December 2021, who met the following criteria: PAPm ≥25 mmHg, PCP≤15 mmHg, PVR &amp;gt;3 UW, age&amp;gt;18 years and had a CPET performed in the same week as the 6MWT. For CPET variables showing statistical significance, optimal cut-off points were determined. The kappa statistic was used to test interrater reliability between low-risk classification with CPET and the 6-minute test using the Kappa index. Finally, the added prognostic power of CPET variables was assessed in low-risk patients according to TM6D (defined as &amp;gt;440 metres) by survival analysis. Results We included a total of 313 patients (27% male). 116 patients (64.8%) walked more than 440 metres at TM6D, this subgroup being significantly younger than those who walked less than 440 metres (42±11 vs 48±16 years) and with a higher proportion of men (34.8% vs 23.4%). In patients who walked more than 440 metres, we applied the CPET model associated with prognosis according to the optimal cut-off points obtained (Eq CO2 VT1 ≥41 and/or peak VO2 &amp;lt;15 ml/kg/min). Of the 116 patients classified as good prognosis by the 6MWT, 84 patients (72%) had altered CPET prognostic values. No substantial reliability was demonstrated between the low-risk classification by CPET and 6MWT (K&amp;lt;0.6 in all cases). Kaplan-Meier survival analysis showed that patients with had Eq CO2 VT1 ≥41 and peak VO2 &amp;lt;15 ml/kg/min had a worse prognosis at 5-year follow-up, despite walking more than 440m 6MWT (Figure 1). Conclusion Young patients may have a good-prognosis 6MWT and, however, be at high-risk of adverse events. A combination of CPET variables has a good predictive value for survival in low-risk 6MWT patients. Performing a CPET is mandatory in these patients to adequately stratify risk. Funding Acknowledgement Type of funding sources: None.

Comparison of clinical and economic burden of pulmonary arterial hypertension patients with and without connective tissue disease treated with macitentan

Abstract Introduction Patients with pulmonary arterial hypertension (PAH) and connective tissue disease (CTD) have a poorer prognosis than those diagnosed with other PAH etiologies. Purpose To compare the clinical and economic burden among PAH patients with and without CTD (PAH-CTD/PAH non-CTD) treated with macitentan. Methods This retrospective study used the Optum Clinformatics DataMart to identify PAH-CTD and PAH non-CTD patients aged ≥18 years and prescribed macitentan from 01JAN2015–30JUN2019. The index date was the date of the first macitentan claim. Patients had to have ≥12 months of continuous enrollment before index and were followed until earliest of macitentan discontinuation, health plan disenrollment, death, or study end. Patients in the PAH-CTD cohort had to have a claim for a CTD condition at any time during the 12-month baseline period. Patients with a baseline claim for any PAH medication, chronic thromboembolic pulmonary hypertension, prior atrial septostomy or lung transplant were excluded. Descriptive analysis comprised means, standard deviations, medians, and interquartile ranges for continuous variables and frequencies and percentages for categorical variables. Multivariable analyses (Cox proportional hazards and generalized linear models) adjusting for baseline characteristics were used to compare time to PAH-related and all-cause hospitalization, disease progression (death, lung transplant, atrial septostomy or addition of intravenous/subcutaneous prostanoids), and PAH- and all-cause related medical (inpatient and outpatient) costs between the two cohorts with PAH non-CTD as reference. Results The analysis included 203 PAH-CTD and 750 PAH non-CTD patients treated with macitentan. Versus PAH non-CTD, PAH-CTD patients were younger, had proportionately more females, and lower Charlson Comorbidity Index (CCI) scores (Table). The proportion of patients with a baseline hospitalization, length of stay and inpatient costs were similar across groups. There were no significant differences observed in time to PAH-related hospitalization (hazard ratio [HR]=0.99; p=0.910), all-cause hospitalization (HR=1.13; p=0.195), or disease progression (HR=1.00; p-value=0.973) for the PAH-CTD cohort (PAH non-CTD as reference). All-cause medical costs were similar between the cohorts ($3,836 per patient per month [PPPM] for PAH CTD vs $3,521 PPPM for PAH non-CTD, p=0.362). PAH-CTD patients incurred higher mean PAH-related medical costs vs PAH non-CTD ($2,806 PPPM vs $1,961 PPPM, p=0.047). Conclusion The study suggests that risk of all-cause and PAH-related hospitalization and disease progression did not differ for PAH-CTD and PAH non-CTD patients. Treatment with macitentan in the real world appears to confer similar clinical benefits in both PAH-CTD and PAH non-CTD groups. All-cause costs did not differ between the two cohorts but PAH-related costs were significantly higher in PAH-CTD patients suggesting an incremental burden associated with CTD. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Janssen Scientific Affairs, LLC

COMPARISON BETWEEN PULMONARY ARTERIAL HYPERTENSION (PAH) RISK ASSESSMENT METHODS, INCLUDING PULMONARY HYPERTENSION OUTCOME RISKS ASSESSMENT (PHORA)

COMPARISON BETWEEN PULMONARY ARTERIAL HYPERTENSION (PAH) RISK ASSESSMENT METHODS, INCLUDING PULMONARY HYPERTENSION OUTCOME RISKS ASSESSMENT (PHORA)

Relevance of comorbidities on initial combination therapy in pulmonary arterial hypertension.

Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy. Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median -45.0%, -30.3%, -24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR.

Lack of concordance between the different exercise test measures used in the risk stratification of patients with pulmonary arterial hypertension.

In pulmonary arterial hypertension (PAH) patients it is essential to perform a prognostic assessment to optimize the treatment. The aim of this study is to evaluate the risk stratification concordance assessed with different exercise test variables in a cohort of PAH patients. A retrospective analysis was performed using patient data registered in the PAH unit. Only those patients in whom the mean time elapsed between the 6-min walking test (6MWT) and the cardiopulmonary exercise test (CPET) was a maximum of 6 months were selected. A total of 140 records from 40 patients were finally analyzed. When it came to assessing the concordance between the two exercise tests in the guidelines (CPET and 6MWT), up to 84.3% of the records did not coincide in terms of the risk stratification. Exclusively considering the CPET parameters, most of the records (75%) failed to include all three variables in the same risk category. When analyzing the VO2 alone, up to 40.7% of the tests yielded different risk classifications depending on whether the parameter was expressed. In conclusion, there is a low concordance between the two proposed exercise tests. These results should be a call for reflection on whether the cut-off points set for the exercise tests proposed for the current risk stratification are adequate to achieve a correct risk stratification or whether they require an appropriate revision.

Evaluation of right ventricular function in patients with pulmonary arterial hypertension by different right ventricular-pulmonary artery coupling methods.

To compare the accuracy of end-systolic elasticity (Ees)/arterial elasticity (Ea) ratio measured by single beat estimation, pressure–volume loop and cardiac magnetic resonance (CMR) combined volume method in patients with pulmonary artery hypertension, and to find a feasible and reliable method to quantitatively evaluate the function of right ventricle in patients with pulmonary artery hypertension. Forty-nine pulmonary artery hypertension patients enrolled between May 2017 and May 2018 in our hospital were retrospectively analyzed. Firstly, measure Ees/Ea ratio by single beat estimation, pressure–volume loop and CMR combined volume method, then, compare Ees/Ea ratio with New York Heart Association (NYHA) classification and NT-proBNP value respectively to evaluate the accuracy of the 3 methods. Ees/Ea ratio measured by single beat estimation is 2.07 ± 1.01, correlation analysis is not statistically significant when compare with NYHA classification and NT-proBNP value (P > .05). Ees/Ea ratio measured by pressure–volume loop is 2.64 ± 1.48, correlation analysis is not statistically significant when compare with NYHA classification and NT-proBNP value (P > .05). Ees/Ea ratio measured by CMR combined volume method is 0.72 ± 0.43, correlation analysis is statistically significant when compare with NYHA classification and NT-proBNP with negative correlation (P < .05). Ees/Ea ratio decrease according to the increase of NT-proBNP value and the NYHA classification. There is linear regression equation between Ees/Ea ratio measured by CMR combined volume method and log (NT-proBNP) value: Y = –0.257X + 1.45, and the linear regression equation is statistically significant (P = .001). Ees/Ea ratio measured by CMR combined volume method is a feasible and reliable method to quantitatively evaluate the function of right ventricule in patients with pulmonary artery hypertension, which might be further verified in a larger patient population.

The Role of Pulmonary Function Test for Pulmonary Arterial Hypertension in Patients with Connective Tissue Disease.

Objective: The study aimed to investigate the value of pulmonary function test (PFT) in evaluating and predicting pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD). Methods: This was a prospective observational study recruiting patients diagnosed with CTD-PAH. Patients with interstitial lung disease and pulmonary hypertension induced by other causes were not eligible for enrollment. All patients were assessed for PAH every 1–3 months. A patient was considered to have clinical improvement if the grade of risk stratification declined or at least two parameters improved during follow-up, otherwise no improvement. Results: A total of 31 patients with CTD-PAH were recruited in this study. Nearly 70% of patients had declined forced vital capacity (FVC), 60% had declined total lung capacity and maximum expiratory flow at 50% of vital capacity, and 95% had normal or mild decline in forced expiratory volume in 1 second (FEV1)/FVC. A decline in diffusing capacity of the lung for carbon monoxide (DLCO) was present in 96% of patients, and 60% were moderate to severe. Furthermore, 50% of patients had an FVC/DLCO ratio of less than 1.4. Univariate analysis showed that FEV1/FVC, DLCO, and FVC/DLCO were associated with disease prognosis. After adjusting for age as a confounding factor, multivariate logistic regression analysis revealed that DLCO was an independent predictive factor for the prognosis of CTD-PAH. Conclusion: The pulmonary function of patients with CTD-PAH is abnormal in parameters such as lung volume, small airway, and gas exchange. PFT can reveal complex pathophysiological changes in the lungs of CTD-PAH patients and predict prognosis.

Analysis of interactions between cardiovascular oscillations for discrimination of early vascular disorders in arterial hypertension and type 2 diabetes

ObjectiveEarly identification of blood flow regulation disturbances allows developing new diagnostic methods for the predictive and personalized medicine in cardiovascular diseases. Comprehensive analysis of interactions between cardiovascular oscillations was proposed to reveal vascular disorders in arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) patients. MethodsHeart rate variability (HRV), forearm and foot skin blood flow (SBF) were registered simultaneously at rest and under postural exposure in controls, AH and T2DM patients. Spectral components of signals, group wavelet phase coherence (gWPC) and Spearman's rank correlations were evaluated. Receiver Operating Characteristic curve analysis was applied to reveal the most effective predictors of cardiovascular system state. ResultsIn patients, spectral amplitudes of foot SBF was lower in low and high frequency ranges at rest and under postural test than forearm SBF. In controls these parameters were lower only in high frequency ranges versus forearm. HRV spectral components were lower at rest in T2DM and under test in all patients. For all signal pairs gWPC decreased in low frequency interval at rest and during test in patients. Correlations were higher on forearm in AH and on foot in T2DM during test. gWPC and correlations were the most effective to distinguish patients from controls. Correlations had high discriminative power to differentiate AH and T2DM patients. ConclusionAnalysis of interactions between cardiovascular oscillations can be used as an effective instrument for clinical application in prognosis and diagnosis of early pathophysiological changes in cardiovascular system in response to various exposure and under different pathologies.

Prediction of Risk Takers in Arterial Hypertension Patients with Data Mining Application

Hyper arterial pressure (HAP) is a disease that kills silently because it does not produce symptoms in the early stages, making it difficult to diagnose. When it is detected, its treatment is not accessible to everyone, which affects the disease’s long-term development. Hypertension affects a large portion of the Iraqi population. In the current research paper, we have discussed how data mining can be applied to identify the status of the risk factors that affect arterial hypertension due to I10-I15 causes, evaluating the context variables disability, overwork, high-risk pregnancy, stress, high diets, and poor nutrition in the population between 50 and 64 years in the city of Baghdad. It is possible to see how data mining in large volumes of health data can generate new knowledge and thus uncover hidden patterns in the data through the development of this research. Attributes directly linked to disease prevalence can be found in data from Baghdad, Iraq, even if they are not directly linked to a specific cause. This shows that some variables are transversal to the development of the disease regardless of its categorization. Cluster analysis revealed that, even though these diseases are categorized as having different causes, they have a degree of incorrect classification of 40.71% because they present attributes with a similar behavior transversal to the disease and not the disease-specific cause for which it is categorized.

Endothelial senescence mediates hypoxia-induced vascular remodeling by modulating PDGFB expression.

Uncontrolled accumulation of pulmonary artery smooth muscle cells (PASMCs) to the distal pulmonary arterioles (PAs) is one of the major characteristics of pulmonary hypertension (PH). Cellular senescence contributes to aging and lung diseases associated with PH and links to PH progression. However, the mechanism by which cellular senescence controls vascular remodeling in PH is not fully understood. The levels of senescence marker, p16INK4A and senescence-associated β-galactosidase (SA-β-gal) activity are higher in PA endothelial cells (ECs) isolated from idiopathic pulmonary arterial hypertension (IPAH) patients compared to those from healthy individuals. Hypoxia-induced accumulation of α-smooth muscle actin (αSMA)-positive cells to the PAs is attenuated in p16fl/fl-Cdh5(PAC)-CreERT2 (p16iΔEC) mice after tamoxifen induction. We have reported that endothelial TWIST1 mediates hypoxia-induced vascular remodeling by increasing platelet-derived growth factor (PDGFB) expression. Transcriptomic analyses of IPAH patient lungs or hypoxia-induced mouse lung ECs reveal the alteration of senescence-related gene expression and their interaction with TWIST1. Knockdown of p16INK4A attenuates the expression of PDGFB and TWIST1 in IPAH patient PAECs or hypoxia-treated mouse lungs and suppresses accumulation of αSMA–positive cells to the supplemented ECs in the gel implanted on the mouse lungs. Hypoxia-treated mouse lung EC-derived exosomes stimulate DNA synthesis and migration of PASMCs in vitro and in the gel implanted on the mouse lungs, while p16iΔEC mouse lung EC-derived exosomes inhibit the effects. These results suggest that endothelial senescence modulates TWIST1-PDGFB signaling and controls vascular remodeling in PH.

Selexipag-based triple combination therapy improves prognosis in Chinese pulmonary arterial hypertension patients.

AimSelexipag is an oral selective prostacyclin receptor agonist approved for treatment of patients with pulmonary arterial hypertension (PAH). In the present study, we aim to assess the safety and efficacy of selexipag in triple combination therapy with endothelial receptor antagonists (ERAs) and PDE5is for Chinese PAH patients.Methods and resultsA single center retrospective study was performed on group 1 PAH patients (n = 68) initiating triple combination therapy with selexipag from 1 February 2020 to 31 August 2021 in Qilu Hospital of Shandong University (Shandong, China). Adolescents, children, and PAH patients with unrepaired congenital heart disease were excluded. The French pulmonary hypertension network (FPHN) non-invasive risk assessment, echocardiogram parameters, and clinical data, including tolerability, safety, and death/hospitalization events associated with PAH, were collected. Of the 68 patients, 31 (45.6%) patients had tolerable side effects while only a single patient discontinued selexipag due to severe diarrhea. In the analysis of the efficacy set of 62 patients, the median selexipag treatment time from selexipag initiation to last risk assessment was 27 (21, 33) weeks. Compared to baseline parameters, the percentage of WHO FC III/IV decreased from 77.4% (48) to 24.2% (15) (p = 0.000), median 6-min walk distance (6MWD) increased 82 m [from 398 (318, 450) to 480 (420, 506) m; p = 0.000], and NT-proBNP levels decreased from 1,216 (329, 2,159) to 455 (134, 1,678) pg/mL (p = 0.007). Patients who improved to three low-risk criteria increased from 9.7 to 38.7%. Right ventricular diameter (RV) diameter also decreased and was accompanied by an improved tricuspid annular plane systolic excursion (TAPSE). Patients transitioning from subcutaneous treprostinil to selexipag continued to show improvements in WHO FC, 6MWD (404 ± 94 vs. 383 ± 127 m) and NT-proBNP levels (2,319 ± 2,448 vs. 2,987 ± 3,770 pg/mL). Finally, the 1-year event free survival rate was 96.7% for patients initiating the triple combination therapy within 3 years of PAH diagnosis.ConclusionTriple combination therapy with selexipag was safe and effective in Chinese PAH patients, which was confirmed by acceptable tolerability, and improved exercise capacity, right heart function, risk assessment, and prognosis.