Effect of Supervised Training Therapy on Pulmonary Arterial Compliance and Stroke Volume in Severe Pulmonary Arterial Hypertension and Inoperable or Persistent Chronic Thromboembolic Pulmonary Hypertension

Background: Pulmonary arterial compliance (PAC) is a prognostic parameter in pulmonary arterial hypertension (PAH) reflecting the elasticity of the pulmonary vessels. Objectives: The objective of this post hoc analysis of a prospective randomized controlled trial (RCT) was to assess the effect of exercise training on PAC and stroke volume (SV) in patients with PAH and persistent/inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Method: From the previous RCT, 43 out of 87 patients with severe PAH (n = 29) and CTEPH (n = 14) had complete haemodynamic examinations at baseline and after 15 weeks by right heart catheterization and were analysed (53% female, 79% World Health Organization functional class III/IV, 58% combination therapy, 42% on supplemental oxygen therapy, training group n = 24, and control group n = 19). Medication remained unchanged for all patients. Results: Low-dose exercise training at 4-7 days/week significantly improved PAC (training group 0.33 ± 0.65 mL/mm Hg vs. control group -0.06 ± 1.10 mL/mm Hg; mean difference 0.39 mL/mm Hg, 95% confidence interval [CI] 0.15-0.94 mL/mm Hg; p = 0.004) and SV (training group 9.9 ± 13.4 mL/min vs. control group -4.2 ± 11.0 mL/min; mean difference 14.2 mL, 95% CI 6.5-21.8 mL; p < 0.001) in the training versus control group. Furthermore, exercise training significantly improved cardiac output and pulmonary vascular resistance at rest, peak oxygen consumption, and oxygen pulse. Conclusions: Our findings suggest that supervised exercise training may improve right ventricular function and PAC at the same time. Further prospective studies are needed to evaluate these findings

Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial

Aims This prospective, randomized, controlled, multicentre study aimed to evaluate efficacy and safety of exercise training in patients with pulmonary arterial (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).Methods and results For the first time a specialized PAH/CTEPH rehabilitation programme was implemented in 11 centres across 10 European countries. Out of 129 enrolled patients, 116 patients (58 vs. 58 randomized into a training or usual care control group) on disease-targeted medication completed the study [85 female; mean age 53.6 +/- 12.5 years; mean pulmonary arterial pressure 46.6 +/- 15.1 mmHg; World Health Organization (WHO) functional class II 53%, III 46%; PAH n= 98; CTEPH n= 18]. Patients of the training group performed a standardized in-hospital rehabilitation with mean duration of 25 days [95% confidence interval (CI) 17-33 days], which was continued at home. The primary endpoint, change of 6-min walking distance, significantly improved by 34.1 +/- 8.3 m in the training compared with the control group (95% CI, 18-51 m; P < 0.0001). Exercise training was feasible, safe, and well-tolerated. Secondary endpoints showed improvements in quality of life (short-form health survey 36 mental health 7.3 +/- 2.5, P = 0.004), WHO-functional class (training vs. control: improvement 9:1, worsening 4:3; chi(2) P =0.027) and peak oxygen consumption (0.9 +/- 0.5 mL/min/kg, P =0.048) compared with the control group.Conclusion This is the first multicentre and so far the largest randomized, controlled study on feasibility, safety, and efficacy of exercise training as add-on to medical therapy in PAH and CTEPH. Within this study, a standardized specialized training programme with in-hospital start was successfully established in 10 European countries.[GRAPHICS]

Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial

Aims This prospective, randomized, controlled, multicentre study aimed to evaluate efficacy and safety of exercise training in patients with pulmonary arterial (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).Methods and results For the first time a specialized PAH/CTEPH rehabilitation programme was implemented in 11 centres across 10 European countries. Out of 129 enrolled patients, 116 patients (58 vs. 58 randomized into a training or usual care control group) on disease-targeted medication completed the study [85 female; mean age 53.6 +/- 12.5 years; mean pulmonary arterial pressure 46.6 +/- 15.1 mmHg; World Health Organization (WHO) functional class II 53%, III 46%; PAH n= 98; CTEPH n= 18]. Patients of the training group performed a standardized in-hospital rehabilitation with mean duration of 25 days [95% confidence interval (CI) 17-33 days], which was continued at home. The primary endpoint, change of 6-min walking distance, significantly improved by 34.1 +/- 8.3 m in the training compared with the control group (95% CI, 18-51 m; P < 0.0001). Exercise training was feasible, safe, and well-tolerated. Secondary endpoints showed improvements in quality of life (short-form health survey 36 mental health 7.3 +/- 2.5, P = 0.004), WHO-functional class (training vs. control: improvement 9:1, worsening 4:3; chi(2) P =0.027) and peak oxygen consumption (0.9 +/- 0.5 mL/min/kg, P =0.048) compared with the control group.Conclusion This is the first multicentre and so far the largest randomized, controlled study on feasibility, safety, and efficacy of exercise training as add-on to medical therapy in PAH and CTEPH. Within this study, a standardized specialized training programme with in-hospital start was successfully established in 10 European countries.[GRAPHICS]

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry

The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; &lt;45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward&apos;s minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p &lt; 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival. © 2020 The Author

Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry

Aims: Dilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non-familial (sporadic) DCM (SDCM) across Europe. Methods and results: Patients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P\ua0<\ua00.01), had less severe disease phenotype at presentation (P\ua0<\ua00.02), more favourable baseline cardiovascular risk profiles (P\ua0 64\ua00.007), and less medication use (P\ua0 64\ua00.042). Outcome at 1\ua0year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25\u20130.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02\u20131.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P\ua0<\ua00.01) and had higher genetic yield (55% vs. 22%, P\ua0<\ua00.01). Conclusions: We observed that FDCM and SDCM have significant differences at baseline but similar short-term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non-marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence

Heart failure in Europe: Guideline-directed medical therapy use and decision making in chronic and acute, pre-existing and de novo, heart failure with reduced, mildly reduced, and preserved ejection fraction – the ESC EORP Heart Failure III Registry

Aims We analysed baseline characteristics and guideline-directed medical therapy (GDMT) use and decisions in theEuropean Society of Cardiology (ESC) Heart Failure (HF) III Registry. Methods and results Between1November 2018and31December 2020,10162 patients with acute HF (AHF, 39%, age 70 [62-79],36% women) or outpatient visit for HF (61%, age 66 [58-75], 33% women), with HF with reduced (HFrEF, 57%),mildly reduced (HFmrEF,17%) or preserved (HFpEF, 26%) ejection fraction were enrolled from 220 centres in 41European or ESC-affiliated countries. With AHF, 97% were hospitalized, 2.2% received intravenous treatment in theemergency department, and 0.9% received intravenous treatment in an outpatient clinic. AHF was seen by most bya general cardiologist (51%) and outpatient HF most by a HF specialist (48%). A majority had been hospitalized forHF before, but 26% of AHF and 6.1% of outpatient HF had de novo HF. Baseline use, initiation and discontinuation ofGDMT varied according to AHF versus outpatient HF, de novo versus pre-existing HF, and by ejection fraction. Afterthe AHF event or outpatient HF visit, use of any renin-angiotensin system inhibitor, angiotensin receptor-neprilysininhibitor, beta-blocker, mineralocorticoid receptor antagonist and loop diuretics was 89%, 29%, 92%, 78%, and 85%in HFrEF; 89%, 9.7%, 90%, 64%, and 81% in HFmrEF; and 77%, 3.1%, 80%, 48%, and 80% in HFpEF. ConclusionUse and initiation of GDMT was high in cardiology centres in Europe, compared to previous reports from cohortsand registries including more primary care and general medicine and regions more local or outside of Europe andESC-affiliated countries....................................