Pulmonary arterial hypertension in systemic sclerosis: a national inpatient analysis.

OBJECTIVES: We aim to study the prevalence and epidemiology of pulmonary arterial hypertension in SS, and the impact of PAH on SSc hospitalizations in the United States population. METHODS: We utilized the National Inpatient Sample (NIS) from 2016-2019 to obtain adult hospitalizations with the primary/secondary diagnosis of SSc and coexistent PAH (SSc-PAH). Epidemiological variables, mortality rates, and secondary outcomes were studied including pulmonary embolism, atrial flutter, atrial and ventricular fibrillation, pneumonia, sepsis, cardiac arrest and cardiac & renal failure, and ventilator requirement. Healthcare burden was estimated from total hospital charges (THC) and length of stay (LOS). Statistical analysis was performed on STATA 16.1, using linear and logistic regression analyses. RESULTS: Out of 126,685 adult systemic sclerosis hospitalizations, 16.89% had PAH (SSc-PAH). The SSc-PAH group had significantly more females (85.4 % vs. 83.8%) and higher mean age (64.85±13.29 vs. 62.56±14.51). More African Americans were in this group than in the control group (19.5% vs. 14.6, p-value<0.001) while Whites (61.3% vs. 65.6%, p<0.001) and Asians (18.0 % vs. 2.8%, p<0.001) were less common. Charlson comorbidity index was higher for the SSc-PAH population (3.42 vs. 2.94, p-value<0.001). SSc-PAH group had a higher adjusted odds ratio (aOR) for mortality (aOR: 1.39, p<0.001), increased LOS (6.64 vs. 6.0 days, p<0.001) increased THC ($83,813 vs. $71,016, p <0.001). For the SSc-PAH group, there were also significantly higher odds of cardiac failure (aOR 3.13), ventilator requirement (aOR 2.15), cardiac arrest (aOR 1.39), kidney failure (aOR 1.63), pulmonary embolism (aOR 1.84), atrial flutter (aOR 1.86) atrial fibrillation (aOR1.56) and pneumonia (aOR 1.22). No significant difference in ventricular fibrillation, sepsis, or respiratory failure was noted. CONCLUSION: Pulmonary arterial hypertension in SSc is associated with worse outcomes in terms of mortality and morbidity, and higher healthcare burden compared to SSc without PAH. Also, PAH disproportionately affects White, African American & Asian populations. There remains a pressing need to continue efforts for early diagnosis and management of PAH in SSc patients.

Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. METHODS: Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. RESULTS: Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P < .0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P < .001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P = .001), shorter 6-min walk distance (P = .001), and reduced cardiac performance (cardiac index, P = .016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P = .0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27-5.33; P < .0087). Comparisons of ML-derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62-0.79) for PAH. CONCLUSIONS: This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification.

Prognostic Significance of Proteomics-Discovered Circulating Inflammatory Biomarkers in Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) ultimately leads to right ventricular failure and premature death. The identification of circulating biomarkers with prognostic utility is considered a priority. As chronic inflammation is recognized as key pathogenic driver, we sought to identify inflammation-related circulating proteins that add incremental value to current risk stratification models for long-term survival in patients with PAH. METHODS AND RESULTS: Plasma levels of 384 inflammatory proteins were measured with the proximity extension assay technology in patients with PAH (n=60) and controls with normal hemodynamics (n=28). Among these, 51 analytes were significantly overexpressed in the plasma of patients with PAH compared with controls. Cox proportional hazard analyses and C-statistics were performed to assess the prognostic value and the incremental prognostic value of differentially expressed proteins. A panel of 6 proteins (CRIM1 [cysteine rich transmembrane bone morphogenetic protein regulator 1], HGF [hepatocyte growth factor], FSTL3 [follistatin-like 3], PLAUR [plasminogen activator, urokinase receptor], CLSTN2 [calsyntenin 2], SPON1 [spondin 1]) were independently associated with death/lung transplantation at the time of PAH diagnosis after adjustment for the 2015 European Society of Cardiology/European Respiratory Society guidelines, the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) 2.0 risk scores, and the refined 4-strata risk assessment. CRIM1, PLAUR, FSTL3, and SPON1 showed incremental prognostic value on top of the predictive models. As determined by Western blot, FSTL3 and SPON1 were significantly upregulated in the right ventricle of patients with PAH and animal models (monocrotaline-injected and pulmonary artery banding-subjected rats). CONCLUSIONS: In addition to revealing new actors likely involved in cardiopulmonary remodeling in PAH, our screening identified promising circulating biomarkers to improve risk prediction in PAH, which should be externally confirmed.

Prognostic Value of Serial Risk Stratification in Adult and Pediatric Pulmonary Arterial Hypertension: A Systematic Review.

BACKGROUND: In pulmonary arterial hypertension, it is recommended to base therapeutic decisions on risk stratification. This systematic review aims to report the prognostic value of serial risk stratification in adult and pediatric pulmonary arterial hypertension and to explore the usability of serial risk stratification as treatment target. METHODS AND RESULTS: Electronic databases PubMed, Embase, and Web of Science were searched up to January 30, 2023, using terms associated with pulmonary arterial hypertension, pediatric pulmonary hypertension, and risk stratification. Observational studies and clinical trials describing risk stratification at both baseline and follow-up were included. Sixty five studies were eligible for inclusion, including only 2 studies in a pediatric population. C-statistic range at baseline was 0.31 to 0.77 and improved to 0.30 to 0.91 at follow-up. In 53% of patients, risk status changed (42% improved, 12% worsened) over 168 days (interquartile range, 137-327 days; n=22 studies). The average proportion of low-risk patients increased from 18% at baseline to 36% at a median follow-up of 244 days (interquartile range, 140-365 days; n=40 studies). In placebo-controlled drug studies, risk statuses of the intervention groups improved more and worsened less compared with the placebo groups. Furthermore, a low-risk status, but also an improved risk status, at follow-up was associated with a better outcome. Similar results were found in the 2 pediatric studies. CONCLUSIONS: Follow-up risk stratification has improved prognostic value compared with baseline risk stratification, and change in risk status between baseline and follow-up corresponded to a change in survival. These data support the use of serial risk stratification as treatment target in pulmonary arterial hypertension.

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.

Prognostic value of pulmonary diffusing capacity for carbon monoxide and ventilation-perfusion SPECT findings in pulmonary arterial hypertension.

Reduced pulmonary diffusing capacity for carbon monoxide (DLCO) can be observed in pulmonary arterial hypertension (PAH) and associates with increased mortality. However, the prognostic value of DLCO when corrected for haemoglobin (DLCOc), an independent modifier of DLCO, remains understudied. Additionally, the prognostic role of ventilation (V)-perfusion (Q) emission computed tomography (V/Q SPECT) findings in patients with PAH, which may concurrently be performed to rule out chronic thromboembolic pulmonary hypertension, is uncertain. A retrospective cohort study was conducted on 152 patients with PAH referred to a tertiary hospital for evaluation from January 2011 to January 2020. Lung function tests, clinical data and V/Q SPECT were ascertained. Cox regression analysis was performed to evaluate the association between DLCOc, DLCO and V/Q SPECT defects at referral with all-cause mortality. In equally adjusted Cox regression analysis, each percentage increase in DLCOc % predicted (%pred) (hazard ratio (HR) 0.97; 95% CI: 0.94-0.99) and DLCO%pred (HR 0.97; 95% CI: 0.94-0.99) was similarly associated with all-cause mortality. There was no detectable difference in area under the curve for prediction of all-cause mortality by DLCOc%pred and DLCO%pred (C-index 0.71 and 0.72, respectively, P = 0.85 for difference). None of the defects noted on V/Q SPECT were significantly associated with mortality, but mismatched defects were associated with lower values of DLCOc%pred and DLCO%pred. DLCOc%pred and DLCO%pred perform equally as prognostic markers in PAH, supporting the use of either metric when available for prognostic stratification.

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

BACKGROUND: Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. METHODS: Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. RESULTS: Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. CONCLUSIONS: Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

Survival in systemic sclerosis associated pulmonary arterial hypertension in the current treatment era-results from a nationwide study.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). This nationwide study aims to describe real world treatment characteristics and assess survival rates of patients with SSc-PAH. METHODS: In this retrospective cohort study, patients with SSc-PAH were identified from Turkish Ministry of Health National Electronic Database (from January 2016 to September 2022), using ICD-10 codes. Data on demographics, treatment characteristics, and death was collected. Kaplan-Meier curves were used to calculate cumulative probabilities of survival at 1, 3, and 5 years. RESULTS: Five hundred forty-seven patients (90.7% female) with SSc-PAH were identified. Median age at PAH diagnosis was 59.9 (50.0-67.4) years. During a median follow-up duration of 3.2 (1.5-4.8) years, 199 (36.4%) deaths occurred. Estimated survival rates at 1, 3, and 5 years were 90.2%, 73.2%, and 56.6%, respectively. Survival was similar among patients with and without interstitial lung disease (p = 0.20). Patients who used immunosuppressives had better survival than those who did not (p < 0.001). No difference was observed in survival rates according to initial PAH-specific treatment regimen (monotherapy or combination) (p = 0.49). CONCLUSION: Compared to most of historical cohorts, higher survival rates for SSc-PAH were observed in this study. Early diagnosis of PAH may have contributed to these findings. The impact of immunosuppressive therapy on prognosis of SSc-PAH needs to be further investigated in prospective studies. Key Points • Early diagnosis is pivotal for better outcomes in SSc-PAH. • Implementation of PAH treatment guidelines in routine clinical practice is still poor and should be improved. • Effect of immunosuppressive therapies on disease course has to be defined in SSc-PAH.

Evaluation of the European Society of Cardiology Risk Assessment Score in Incident Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

OBJECTIVE: Patients with pulmonary arterial hypertension (PAH) may be stratified as low, intermediate, or high risk of 1-year mortality. In 2022, the European Society of Cardiology (ESC) updated and simplified its risk stratification tool, based on three variables: World Health Organization functional class, serum N-terminal pro-brain type natriuretic peptide and six-minute walk distance, applied at follow-up visits, intended to guide therapy over time. METHODS: We applied the 2022 ESC risk assessment tool at baseline and follow-up (within 2 years) to a multinational incident cohort of systemic sclerosis-associated PAH (SSc-PAH). Kaplan-Meier curves, Cox hazards regression, and accelerated failure time models were used to evaluate survival by risk score. RESULTS: At baseline (n = 260), the majority of SSc-PAH (72.2%) were graded as intermediate risk of death according to the 2022 tool. At follow-up, according to 2022 tool, half (55.5%) of the cohort were classified as low or intermediate-low risk. The 2022 risk model at follow-up was able to differentiate survival between risk strata. All three individual parameters (World Health Organization functional class, N-terminal pro-brain type natriuretic peptide, six-minute walk distance) were significantly associated with mortality at baseline and/or follow-up. CONCLUSION: The 2022 ESC risk assessment strategy applied at baseline and follow-up predicts survival in SSc-PAH. Treatment decisions for SSc-PAH should include risk assessments, aiming to achieve low-risk status according to the 2022 ESC guidelines.

Investigating the "sex paradox" in pulmonary arterial hypertension: Results from the Pulmonary Hypertension Association Registry (PHAR).

BACKGROUND: Female sex is a significant risk factor for pulmonary arterial hypertension (PAH), yet males with PAH have worse survival - a phenomenon referred to as the "sex paradox" in PAH. METHODS: All adult PAH patients in the Pulmonary Hypertension Association Registry (PHAR) with congruent sex and gender were included. Baseline differences in demographics, hemodynamics, functional parameters, and quality of life were assessed by sex. Kaplan-Meier survival analysis was used to evaluate survival by sex. Mediation analysis was conducted with Cox proportional hazards regression by comparing the unadjusted hazard ratios for sex before and after adjustment for covariates. The plausibility of collider-stratification bias was assessed by modeling how large an unmeasured factor would have to be to generate the observed sex-based mortality differences. Subgroup analysis was performed on idiopathic and incident patients. RESULTS: Among the 1,891 patients included, 75% were female. Compared to men, women had less favorable hemodynamics, lower 6-minute walk distance, more PAH therapies, and worse functional class; however, sex-based differences were less pronounced when accounting for body surface area or expected variability by gender. On multivariate analysis, women had a 48% lower risk of death compared to men (Hazard Ratio 0.52, 95% Confidence interval 0.36 - 0.74, p < 0.001). Modeling found that under reasonable assumptions collider-stratification could account for sex-based differences in mortality. CONCLUSIONS: In this large registry of PAH patients new to a care center, men had worse survival than women despite having more favorable baseline characteristics. Collider-stratification bias could account for the observed greater mortality among men.

Long-term efficacies of selective vasodilators in pulmonary arterial hypertension: a comprehensive comparison using a spontaneous reporting database.

There is no clinical evidence of differences in drugs associated with long-term survival in patients with pulmonary arterial hypertension (PAH) due to the small population and lack of information on death in Japanese medical database systems. This study evaluated whether patient data from a spontaneous reporting database could be used for comparing the effects of pulmonary vasodilators on long-term survival in PAH patients. PAH patient data reported in the Japanese Adverse Drug Event Report (JADER) database from April 2004 to July 2022 were extracted. Kaplan-Meier curves were used to compare survival times. Adjusted hazard ratios (aHRs) for all-cause mortality were determined using Cox proportional hazards models. Of 1969 PAH patients reported in the JADER database, 1208 were included in the survival analyses. The patient demographics were similar to those of the PAH population reported in the Japan Pulmonary Hypertension Registry. Among drugs targeting the prostacyclin pathway, epoprostenol was most associated with long-term survival (aHR, 0.38; 95% confidence interval (CI), 0.23-0.64). The PAH patients treated with endothelin receptor antagonists had improved survival, especially among the macitentan users (aHR, 0.30; 95% CI, 0.22-0.42). Sildenafil was associated with a poor prognosis in the PAH patients (aHR, 1.56; 95% CI, 1.19-2.04). Although our results must be interpreted with caution due to several limitations inherent to spontaneous reporting databases, our approach using the JADER database for survival analysis may provide useful information in limited situations such as the treatment of rare diseases including PAH.

The soluble receptor for advanced glycation end products is potentially predictive of pulmonary arterial hypertension in systemic sclerosis.

Introduction: Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are the leading causes of death in systemic sclerosis (SSc). Until now, no prospective biomarker to predict new onset of SSc-ILD or SSc-PAH in patients with SSc has reached clinical application. In homeostasis, the receptor for advanced glycation end products (RAGE) is expressed in lung tissue and involved in cell-matrix adhesion, proliferation and migration of alveolar epithelial cells, and remodeling of the pulmonary vasculature. Several studies have shown that sRAGE levels in serum and pulmonary tissue vary according to the type of lung-related complication. Therefore, we investigated levels of soluble RAGE (sRAGE) and its ligand high mobility group box 1 (HMGB1) in SSc and their abilities to predict SSc-related pulmonary complications. Methods: One hundred eighty-eight SSc patients were followed retrospectively for the development of ILD, PAH, and mortality for 8 years. Levels of sRAGE and HMGB1 were measured in serum by ELISA. Kaplan-Meier survival curves were performed to predict lung events and mortality and event rates were compared with a log-rank test. Multiple linear regression analysis was performed to examine the association between sRAGE and important clinical determinants. Results: At baseline, levels of sRAGE were significantly higher in SSc-PAH-patients (median 4099.0 pg/ml [936.3-6365.3], p = 0.011) and lower in SSc-ILD-patients (735.0 pg/ml [IQR 525.5-1988.5], p = 0.001) compared to SSc patients without pulmonary involvement (1444.5 pg/ml [966.8-2276.0]). Levels of HMGB1 were not different between groups. After adjusting for age, gender, ILD, chronic obstructive pulmonary disease, anti-centromere antibodies, the presence of puffy fingers or sclerodactyly, use of immunosuppression, antifibrotic therapy, or glucocorticoids, and use of vasodilators, higher sRAGE levels remained independently associated with PAH. After a median follow-up of 50 months (25-81) of patients without pulmonary involvement, baseline sRAGE levels in the highest quartile were predictive of development of PAH (log-rank p = 0.01) and of PAH-related mortality (p = 0.001). Conclusions: High systemic sRAGE at baseline might be used as a prospective biomarker for patients with SSc at high risk to develop new onset of PAH. Moreover, high sRAGE levels could predict lower survival rates due to PAH in patients with SSc.

Clinical implications of arterial hypertension in patients with spontaneous coronary artery dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognized cause of acute coronary syndrome. Many patients with SCAD have associated coronary risk factors. However, the implications of arterial hypertension in SCAD patients remain unknown. OBJECTIVE: This study sought to assess the clinical implications of arterial hypertension in a nationwide cohort of patients with SCAD. METHODS: The Spanish SCAD registry (NCT03607981) prospectively enrolled 318 consecutive patients. All coronary angiograms were centrally analyzed to confirm the diagnosis of SCAD. Patients were classified according to the presence of arterial hypertension. RESULTS: One-hundred eighteen patients (37%) had a diagnosis of arterial hypertension. Hypertensive SCAD patients were older (60 ± 12 vs. 51 ± 9 years old) and had more frequently dyslipidemia (56 vs. 23%) and diabetes (9 vs. 3%) but were less frequently smokers (15 vs. 35%) than normotensive SCAD patients (all P < 0.05). Most patients in both groups were female (90 vs. 87%, NS) and female patients with hypertension were more frequently postmenopausal (70 vs. 47%, P < 0.05). Hypertensive SCAD patients had more severe lesions and more frequently multivessel involvement (15 vs. 7%, P < 0.05) and coronary ectasia (19 vs. 7%, P < 0.05) but showed a similar prevalence of coronary tortuosity (34 vs. 26%, NS). Revascularization requirement was similar in both groups (17 vs. 26%, NS) but procedural success was significantly lower (65 vs. 88%, P < 0.05) and procedural-related complications more frequent (65 vs. 41%, P < 0.05) in SCAD patients with hypertension. CONCLUSION: Patients with SCAD and hypertension are older, more frequently postmenopausal and have more coronary risk factors than normotensive SCAD patients. During revascularization SCAD patients with hypertension obtain poorer results and have a higher risk of procedural-related complications (NCT03607981).

Intravenous prostanoids in systemic sclerosis-associated pulmonary arterial hypertension: a single-centre experience.

OBJECTIVES: The current study evaluates survival rates among SSc-associated pulmonary arterial hypertension (SSc-PAH) patients on i.v. prostanoids, and short-term impact of i.v. prostanoids on clinical and haemodynamic parameters. METHODS: Baseline demographics, invasive and non-invasive data, European Society of Cardiology (ESC) score and REVEAL score of 81 SSc-PAH patients (median age 61 years, interquartile range 54-67 years, 84% females) were prospectively recorded, from November 2006 till November 2020, before initiation of i.v. prostanoids, and at first formal reassessment. Survival data were retrieved from National Health Service Spine and hospital databases. RESULTS: Significant improvements in clinical and haemodynamic parameters in response to i.v. prostanoid therapy were documented. Functional class (FC) (16.6% improved by 1FC, P =0.041), mean pulmonary arterial pressure (-6.5 mmHg, P =0.036), pulmonary vascular resistance (-2.6 WU, P =0.012), cardiac index (Q/m2) (+0.7 l/min/m2, P =0.003) and mixed venous oxygen saturation (SvO2) (+3%, P =0.036) improved. Estimated survival for CTD-PAH patients on i.v. prostanoids was 64%, 31% and 18%, at 1 year, 3 years and 5 years, respectively. Independent baseline predictors of mortality were older age (HR: 1.043, 95% CI: 1.011-1.075, P =0.007), higher N-terminal pro-brain natriuretic peptide levels (HR: 2.191, 95% CI: 1.131-4.243, P =0.020), and lower SvO2 levels (HR: 0.962, 95% CI: 0.926-0.998, P =0.039). High ESC risk or high and very high REVEAL score was associated with significantly worse survival compared with patients with lower risk scores, both at baseline and when reassessed after a median of 6.5 months. CONCLUSIONS: Survival among SSc-PAH patients on i.v. prostanoids remains poor, risk scoring at baseline and after 6.5 months of therapy improves prognostication.

Hipertensión pulmonar. Definiendo la estructura y la función departamental a partir del riesgo / Pulmonary hypertension. Defining the structure and the departmental function based on risk

Se presenta un modelo departamental para la atención integral de pacientes con hipertensión pulmonar. Se resume el conocimiento actual de la hipertensión pulmonar, su mortalidad, pronóstico y la estratificación de su severidad que justifican la propuesta de la estructura y la función departamental.

A departmental model for the comprehensive care of patients with pulmonary hypertension is presented. The current knowledge of pulmonary hypertension, its mortality, prognosis and the stratification of its severity that justify the proposal of the departmental structure and function are summarized.

Caracterización de la adherencia terapéutica en adultos mayores hipertensos / Characterization of therapeutic adherence in hypertensive older adults

RESUMEN Introducción: la adherencia terapéutica es un problema multifactorial que ha generado el interés de muchos investigadores a nivel mundial. Objetivo: determinar la adherencia al tratamiento antihipertensivo en pacientes adultos mayores y los factores asociados a la no adherencia. Materiales y métodos: se realizó un estudio descriptivo longitudinal en pacientes adultos mayores hipertensos, pertenecientes al Policlínico Comunitario Sur, del municipio Morón, en la provincia de Ciego de Ávila. La adherencia al tratamiento fue evaluada por el cuestionario Martín-Bayarre-Grau y el nivel de conocimiento de la enfermedad por el Test de Batalla. Se identificaron las causas asociadas a los problemas de adherencia en dichos pacientes. Resultados: Predominó la no adherencia al tratamiento antihipertensivo en un 62 %. La adherencia parcial se constató en un 22 %. Los problemas de adherencia prevalecieron en las féminas de 60-69 años de edad. Se detectaron múltiples causas inherentes al paciente, como el olvido (48,4 %), la no disponibilidad de medicamentos (25,8 %) y el alivio de los síntomas (16,1 %). Entre otras causas se detectó el bajo nivel de conocimiento de la enfermedad y la presencia de comorbilidades. Conclusiones: se evidenció un predominio de adherencia al tratamiento antihipertensivo de los adultos mayores. Sus causas fundamentales fueron el olvido de ingerir el medicamento, la no disponibilidad de medicamentos, la falta de conocimientos sobre la enfermedad y la presencia de comorbilidades (AU).

ABSTRACT Introduction: therapeutic adherence is a multifactorial problem that has generated the interest of many researchers worldwide. Objective: to determine adherence to antihypertensive therapy in older adult patients and the factors associated with no adherence. Materials and methods: a longitudinal descriptive study was carried out in hypertensive elderly patients belonging to the South Community Polyclinic, in the municipality of Moron, in the province of Ciego de Avila. The adherence to treatment was evaluated by the Martín-Bayarre-Grau questionnaire and the level of knowledge of the disease by the Batalla test. The causes associated with adherence problems in these patients were identified. Results: non-adherence to antihypertensive therapy predominated in 62%. Partial adherence was found to be 22%. Adherence problems prevailed in women aged 60-69 years. Multiple causes related with the patient were detected, such as forgetfulness (48.4%), non-availability of medicines (25.8%) and relief of symptoms (16.1%). Among other causes, the low level of knowledge on the disease and the presence of comorbidities were detected. Conclusions: a predominance of adherence to antihypertensive treatment in older adults was evidenced. Its main causes were the forgetfulness of taking the medicine, the non-availability of medicines, the lack of knowledge about the disease and the presence of comorbidities (AU).

Treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by skin and visceral fibrosis, vascular hyperreactivity and obliterative vasculopathy. Some of its complications such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH) and heart involvement can be life-threatening and are associated with a high mortality and a poor prognosis. Many clinical trials were carried out in order to improve the survival and prognosis of SSc patients. The management of SSc is based on the frequent and regular assessment of the potential organ damage, and if present, the establishment of graduated pharmacological therapeutic strategies, associated with non-pharmacological procedures. Several randomized clinical trials have showed significant positive outcomes regarding some specific involvements. Many advances have been made, especially in the field of targeted therapies and personalized medicine, based on specific characteristics of the patient and the SSc.

Association between Initial Treatment Strategy and Long-Term Survival in Pulmonary Arterial Hypertension.

Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) (P < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients (n = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients (n = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.

Is pulmonary vascular resistance index better than pulmonary vascular resistance in predicting outcomes in pulmonary arterial hypertension?

BACKGROUND: In contrast to pulmonary vascular resistance (PVR), PVR index (PVRI) accounts for variations in body habitus. We tested the association of PVRI compared to PVR with clinical outcomes in lean and obese (BMI ≥30 kg/m2) patients with pulmonary arterial hypertension (PAH). METHODS: This retrospective study included adult patients with PAH who underwent right heart catheterization at Cleveland Clinic between February 1992 and November 2019. RESULTS: We included 644 patients (mean age, 53 ± 16 years, and 74 % females). PAH was idiopathic or heritable in 44% of patients. Cardiac output increased (p <0.0001), while PVR decreased (p <0.0001) with increasing body weight. Both PVR and PVRI were associated with markers of disease severity, with more pronounced association for PVRI. Both PVR and PVRI were risk factors for first PAH hospitalization, mortality and mortality or lung transplant in the whole cohort and the group of patients with BMI < 30 kg/m2. However, PVRI (HR (95% CI): 1.06 (1.02 -1.11)), but not PVR (HR (95% CI): 1.03 (0.99-1.07)), was a risk factor for first PAH hospitalization in obese patients. In the obese group, neither PVR nor PVRI were risk factors for mortality. CONCLUSIONS: PVRI appears to have a stronger association than PVR with disease severity markers in PAH; however, both PVR and PVRI were similarly associated with hospitalizations and survival in the overall cohort. We found no strong evidence to recommend a change from PVR to PVRI in the definition of PAH.

Periprocedural safety and outcome after pump implantation for intravenous treprostinil administration in patients with pulmonary arterial hypertension.

METHODS: In this retrospective observational study, we analyzed all patients with pulmonary arterial hypertension undergoing LenusPro® pump implantation between November 2013 and October 2019 at our center. Periprocedural safety was assessed by describing all complications that occurred within 28 days after surgery; complications that occurred later were described to assess long-term safety. Clinical outcomes were measured by comparison of clinical parameters and echocardiographic measurements of right ventricular function from baseline to 6-months-follow-up. RESULTS: Fifty-four patients underwent LenusPro® pump implantation for intravenous treprostinil treatment during the investigation period. Periprocedural complications occurred in 5 patients; the only anesthesia-related complication (right heart failure with recovery after prolonged intensive care and death in the further course) occurred in the only patient who underwent general anesthesia. All other patients underwent local anesthesia with or without short-acting (analgo-) sedation. Eighteen long-term complications occurred in 15 patients, most notably pump pocket or catheter related problems. Transplant-free survival rates at 1, 2, and 3 years were 77 %, 56 %, and 48 %, respectively. CONCLUSIONS: Subcutaneous pump implantation under local anesthesia and conscious analgosedation while avoiding intubation and mechanical ventilation is feasible in patients with advanced PAH. Controlled studies are needed to determine the safest anesthetic approach for this procedure. BACKGROUND/OBJECTIVES: Intravenous treprostinil treatment via a fully implantable pump is a treatment option for patients with advanced pulmonary arterial hypertension. However, there is no consensus on the preferred anesthetic approach for the implantation procedure. Primary objective was to assess periprocedural safety with particular attention to feasibility of local anesthesia and conscious analgosedation instead of general anesthesia. Long-term safety and clinical outcomes were secondary endpoints.