Aims Alveolar gas diffusion (DLCO) is impaired in chronic heart failure (CHF). Diffusion depends on membrane diffusion (DM) and the amount of blood participating in gas exchange (VC). How DM, VC, and the alveolar–capillary unit behave in relationship to CHF severity is unknown. Methods and results We measured pulmonary function, including DLCO, DM, VC, and alveolar volume (VA), in 191 CHF patients in NYHA class I–III. CHF patients were grouped accordingly to peak exercise oxygen uptake (pVO₂): group 20 (n=27). DLCO, DM, VC, and VA were lowest in severe CHF and were linearly related to pV̇O₂ (DLCO, r=0.577, P<0.001; DM, r=0.490, P<0.001; VC, r=0.216, P<0.01; VA, r=0.565, P<0.01). DM/VC ratio, an index of the alveolar–capillary unit efficiency, was higher in group 20 (0.46±0.29), compared with 12–16 (0.34±0.19) and 16–20 (0.35±0.17). Conclusion DLCO progressively worsens as CHF severity increases due to reduction in lung tissue participating to gas exchange (low VC and VA). In severe CHF, the few working alveolar–capillary units are the most efficient as shown by the high DM/VC. This is useful for maintaining gas exchange efficiency in severe CHF.

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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; χ2 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.

Aims: Cardiopulmonary exercise test (CPET) is used to evaluate patients with chronic heart failure (HF) usually by means of a personalized ramp exercise protocol. Our aim was to evaluate if exercise duration or ramp rate influences the results. Methods and results: Ninety HF patients were studied (peak VO2: >20 ml/min/kg, n=28, 15>20 ml/min/kg, n=39 and <15 ml/min/kg, n=23). Each patient did four CPET studies. The initial study was used to separate the subjects into three groups, according to their exercise capacity. In the remaining studies, work-rate was increased at three different rates designed to have the subjects reach peak exercise in 5, 10 and 15 min from the start of the ramp increase in work-rate, respectively. The order was randomized. The work-rate applied for the total population averaged 22.7±8.0, 11.6±3.7, 7.5±2.9 W/min with effective loaded exercise duration of 5 min and 16 s±29 s, 9 min and 43 s±49 s and 14 min and 32 s±1 min and 12 s for the 5-, 10- and 15-min tests, respectively. Peak averaged 16.9±4.3*, 18.0±4.4 and 18.0±5.4 ml/min/kg for the 5-, 10- and 15-min tests, (*=p<0.001 vs. 10 min). The shortest test had the lowest peak heart rate and ventilation and highest peak work-rate. Peak and heart rate were lowest in 5-min tests regardless of HF severity. The δ/δwork-rate was lowest in 5-min tests and highest in 15-min tests. At all ramp rates, δ/δwork-rate was lower for the subjects with the lower peak . The slope and at anaerobic threshold were not affected by the protocol for any grade of HF. Conclusions: In chronic HF, exercise protocol has a small effect on peak and δ/δwork but does not affect at anaerobic threshold and slope.

The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).