Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry

Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension. Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data. Methods and results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients’ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy (n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan–Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; p < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status. Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy

European Society of Cardiology: Cardiovascular Disease Statistics 2017

Background: The European Society of Cardiology (ESC) Atlas has been compiled by the European Heart Agency to document cardiovascular disease (CVD) statistics of the 56 ESC member countries. A major aim of this 2017 data presentation has been to compare high income and middle income ESC member countries, in order to identify inequalities in disease burden, outcomes and service provision. Methods: The Atlas utilizes a variety of data sources, including the World Health Organization, the Institute for Health Metrics and Evaluation, and the World Bank to document risk factors, prevalence and mortality of cardiovascular disease and national economic indicators. It also includes novel ESC sponsored survey data of health infrastructure and cardiovascular service provision provided by the national societies of the ESC member countries. Data presentation is descriptive with no attempt to attach statistical significance to differences observed in stratified analyses. Results: Important differences were identified between the high income and middle income member countries of the ESC with regard to CVD risk factors, disease incidence and mortality. For both women and men, the age-standardised prevalence of hypertension was lower in high income countries (18.3% and 27.3%) compared with middle income countries (23.5% and 30.3%). Smoking prevalence in men (not women) was also lower (26% vs 41.3%), and together these inequalities are likely to have contributed to the higher CVD mortality in middle income countries. Declines in CVD mortality have seen cancer becoming a more common cause of death in a number of high income member countries, but in middle income countries declines in CVD mortality have been less consistent where CVD remains the leading cause of death. Inequalities in CVD mortality are emphasised by the smaller contribution they make to potential years of life lost in high income compared with middle income countries both for women (13% vs. 23%) and men (20% vs. 27%). The downward mortality trends for CVD may, however, be threatened by the emerging obesity epidemic that is seeing rates of diabetes increasing across all ESC member countries. Survey data from the National Cardiac Societies (n=41) showed that rates of cardiac catheterization and coronary artery bypass surgery, as well as the number of specialist centres required to deliver them, were greatest in the high income member countries of the ESC. The Atlas confirmed that these ESC member countries, where the facilities for the contemporary treatment of coronary disease were best developed, were often those in which declines in coronary mortality have been most pronounced. Economic resources were not the only driver for delivery of equitable cardiovascular healthcare, as some middle income ESC member countries reported rates for interventional procedures and device implantations that matched or exceeded the rates in wealthier member countries. Conclusion: In documenting national CVD statistics, the Atlas provides valuable insights into the inequalities in risk factors, healthcare delivery and outcomes of CVD across ESC member countries. The availability of these data will underpin the ESC’s ambitious mission “to reduce the burden of cardiovascular disease” not only in its member countries, but also in nation states around the world

Temporal effects on host-parasite associations in four naturalized goby species living in sympatry

Introduced host species are often characterised by reduced parasite numbers compared to their native populations. Any such advantage gained from parasite release following introduction into a new area may often diminish over a short period as the new host gradually acquires local parasites. In this study, the metazoan parasite communities of four goby species (Proterorhinus semilunaris, Ponticola kessleri, Neogobius melanostomus, and Neogobius fluviatilis) recently introduced into the lower River Rhine were investigated. Mean parasite abundance and infracommunity richness were positively associated with time since host introduction, both parasite variables being the highest in P. semilunaris. In Ponticola and Neogobius species, parasite species richness and the dominance of larval parasites in the Lower Rhine were similar to that for non-native populations in the middle Danube. Sporadic local parasite acquisition and infection, predominantly by species commonly found in the native range, led to a relatively high qualitative similarity in parasite communities between hosts. The relationship between parasite abundance and fish size reflected size-dependant food selectivity and/or parasite accumulation throughout the host's life. Data from this study emphasise the importance of duration of co-occurrence, host habitat and foraging preference, as well as the co-introduction of suitable intermediate hosts, for parasite community composition in related species

Central versus Peripheral CTEPH—Clinical and Hemodynamic Specifications

Background and Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic progressive disease, resulting from persistent arterial obstruction combined with small-vessel remodeling. Central and peripheral CTEPH are distinguished, according to the dominant lesion’s location. This is important for surgical or percutaneous interventional assessment or for medical treatment. Material and Methods: Eighty-one patients (51 male/30 female) with confirmed CTEPH were analyzed, while the CENTRAL type included 51 patients (63%) and the PERIPHERAL type 30 patients (37%). Results: A significant difference in CENTRAL type vs. PERIPHERAL type was determined in gender (male 72.5% vs. 46.7%; p = 0.0198). No difference was found in age, functional status, or echocardiographic parameters. Invasive hemodynamic parameters showed a significant difference in mean pulmonary arterial pressure (46 vs. 58 mmHg; p = 0.0002), transpulmonary gradient (34 vs. 47 mmHg; p = 0.0005), and cardiac index (2.04 vs. 2.5 L.min.m2; p = 0.02) but not in pulmonary vascular resistance. Risk factors showed a significant difference only in acute pulmonary embolism (93.8% vs. 60%; p = 0.0002) and malignancy (2% vs. 13.3%; p = 0.0426). Conclusions: Our study showed hemodynamic differences between CENTRAL type vs. PERIPHERAL type CTEPH with a worse hemodynamic picture in CENTRAL form. This may indicate a different pathophysiological response and/or possible additional influences contributing especially to the peripheral pulmonary bed affection

Characteristics, Management, and Outcomes of Patients with Multiple Native Valvular Heart Disease: A Substudy of the EURObservational Research Programme Valvular Heart Disease II Survey.

Erratum inCorrigendum to: Characteristics, management, and outcomes of patients with multiple native valvular heart disease: a substudy of the EURObservational Research Programme Valvular Heart Disease II Survey. Eur Heart J. 2022 Aug 1;43(29):2813. doi: 10.1093/eurheartj/ehac341.PMID: 35716135International audienceAIMS: To assess the characteristics, management, and survival of patients with multiple native valvular heart disease (VHD). METHODS AND RESULTS: Among the 5087 patients with ≥q1 severe left-sided native VHD included in the EURObservational VHD II Survey (maximum 3-month recruitment period per centre between January and August 2017 with a 6-month follow-up), 3571 had a single left-sided VHD (Group A, 70.2%), 363 had one severe left-sided VHD with moderate VHD of the other ipsilateral valve (Group B, 7.1%), and 1153 patients (22.7%) had ≥q2 severe native VHDs (left-sided and/or tricuspid regurgitation, Group C). Patients with multiple VHD (Groups B and C) were more often women, had greater congestive heart failure (CHF) and comorbidity, higher left atrial volumes and pulmonary pressures, and lower ejection fraction than Group A patients (all P\,≤q\,0.01). During the index hospitalization, 36.7% of Group A (n\,=\,1312), 26.7% of Group B (n\,=\,97), and 32.7% of Group C (n\,=\,377) underwent valvular intervention (P\,<\,0.001). Six-month survival was better for Group A than for Group B or C (both P\,<\,0.001), even after adjustment for age, sex, body mass index, and Charlson index [hazard ratio (HR) 95% confidence interval (CI) 1.62 (1.10-2.38) vs. Group B and HR 95% CI 1.72 (1.32-2.25) vs. Group C]. Groups B and C had more CHF at 6 months than Group A (both P\,<\,0.001). Factors associated with mortality in Group C were age, CHF, and comorbidity (all P\,<\,0.010). CONCLUSION: Multiple VHD is common, encountered in nearly 30% of patients with left-sided native VHD, and associated with greater cardiac damage and leads to higher mortality and more heart failure at 6 months than single VHD, yet with lower rates of surgery

Characteristics, management, and outcomes of patients with multiple native valvular heart disease: a substudy of the EURObservational Research Programme Valvular Heart Disease II Survey

AIMS To assess the characteristics, management, and survival of patients with multiple native valvular heart disease (VHD). METHODS AND RESULTS Among the 5087 patients with ≥1 severe left-sided native VHD included in the EURObservational VHD II Survey (maximum 3-month recruitment period per centre between January and August 2017 with a 6-month follow-up), 3571 had a single left-sided VHD (Group A, 70.2%), 363 had one severe left-sided VHD with moderate VHD of the other ipsilateral valve (Group B, 7.1%), and 1153 patients (22.7%) had ≥2 severe native VHDs (left-sided and/or tricuspid regurgitation, Group C). Patients with multiple VHD (Groups B and C) were more often women, had greater congestive heart failure (CHF) and comorbidity, higher left atrial volumes and pulmonary pressures, and lower ejection fraction than Group A patients (all P ≤ 0.01). During the index hospitalization, 36.7% of Group A (n = 1312), 26.7% of Group B (n = 97), and 32.7% of Group C (n = 377) underwent valvular intervention (P < 0.001). Six-month survival was better for Group A than for Group B or C (both P < 0.001), even after adjustment for age, sex, body mass index, and Charlson index [hazard ratio (HR) 95% confidence interval (CI) 1.62 (1.10-2.38) vs. Group B and HR 95% CI 1.72 (1.32-2.25) vs. Group C]. Groups B and C had more CHF at 6 months than Group A (both P < 0.001). Factors associated with mortality in Group C were age, CHF, and comorbidity (all P < 0.010). CONCLUSION Multiple VHD is common, encountered in nearly 30% of patients with left-sided native VHD, and associated with greater cardiac damage and leads to higher mortality and more heart failure at 6 months than single VHD, yet with lower rates of surgery

The risk profile change in patients with severe chronic thromboembolic pulmonary hypertension treated with subcutaneous treprostinil

Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is successfully treatable with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, and medical therapy. Registry to Evaluate Early and Long‐Term Pulmonary Arterial Hypertension Disease Management risk score (RRS) is able to predict long‐term outcome in inoperable patients or in patients with residual PH after surgery. We performed a post hoc analysis of RRS in patients who were enrolled in the CTREPH study (NCT01416636), a randomized, double‐blind clinical trial comparing high‐dose and low‐dose subcutaneous (SC) treprostinil in patients with severe CTEPH that was classified by an interdisciplinary CTEPH team as nonoperable, or as persistent or recurrent pulmonary hypertension after PEA. Baseline mean RRS was similar in both treatment groups (8.7 in high‐dose arm vs. 8.6 in low‐dose arm), but mean RRS change from baseline to Week 24 was greater in the high‐dose treprostinil group than in the low‐dose treprostinil group (−0.88 vs. −0.17). The difference in RRS change from baseline to Week 24 between high dose versus low dose was statistically significant with mean difference of −0.70 (95% confidence interval: −1.36 to −0.05, p = 0.0352), and was driven mainly by improvement of World Health Organization functional class and N‐terminal pro‐brain natriuretic peptide concentration. SC treprostinil therapy administered in standard dose had positive effect on the risk profile measured by RRS in patients with inoperable or persistent/recurrent severe CTEPH. Although our study was limited by the small sample size and post hoc nature, assessment of risk profile is of great importance to this particular patient population with very poor prognosis

Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry

Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%- 60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and hemodynamics. A history of acute pulmonary embolism was reported for 74.8% of patients (77.5% operable, 70.0% nonoperable). Associated conditions included thrombophilic disorder in 31.9% (37.1% operable, 23.5% nonoperable) and splenectomy in 3.4% of patients (1.9% operable, 5.7% nonoperable). At the time of CTEPH diagnosis, 37.7% of patients initiated at least 1 pulmonary arterial hypertension-targeted therapy (28.3% operable, 53.8% nonoperable). Pulmonary endarterectomy was performed with a 4.7% documented mortality rate. Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions. Operability rates vary considerably across countries, and a substantial number of patients (operable and nonoperable) receive off-label pulmonary arterial hypertension-targeted treatment

Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Results From an International Prospective Registry

-Chronic thromboembolic pulmonary hypertension (CTEPH), a rare complication of acute pulmonary embolism, is characterized by fibro-thrombotic obstructions of large pulmonary arteries combined with small vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated CTEPH patients.status: publishe