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Exercise training in pulmonary hypertension: more beneficial than first thought
Exercise training has historically been discouraged in the pulmonary hypertension due to concerns regarding severe adverse events such as dysrhythmia, syncope and death but more recent data have suggested possible benefits. Grünig et al (ESC 2021;42: 2284) present a prospective, multicentre randomised control trial evaluating the efficacy and safety of standardised exercise training in group I and intravenous pulmonary hypertension. The primary endpoint was change in 6 min walk distance (6MWD) at 15 weeks. Of 129 enrolled patients, 116 predominantly female patients (73.3%) with WHO-FC II–III completed the study; randomised in a 1:1 ratio. The exercise group received inpatient exercise training for 10–30 days and continued at home for 11–12 weeks. The exercise group displayed significant improvement in 6MWD (corrected change 34.1±8.3 m; p<0.0001). Quality of life scores (7.3±2.5; p=0.004), systolic pulmonary artery pressure (9.8±3.1 mm Hg; p=0.002) and peak oxygen consumption (0.9±0.3 mL/min/kg; p=0.048) also improved. Other echocardiographic and cardiopulmonary exercise test parameters did not differ significantly. Although the total number of adverse events were similar between groups, the exercise group reported a higher number of serious adverse events (ie, decompensated diabetes and generalised oedema). These were not identified as being directly related to exercise. While the study provides positive reassurance regarding the safety of standardised exercise training, the longer-term benefits remain unknown. The study cannot fully exclude the potential for inclusion bias among a more adherent patient cohort.
Acute pulmonary embolism: not as acute as we might think?
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but serious complication following acute pulmonary embolism (PE). Barco et al (Chest 2023;163:923) present an observational multicentre cohort study identifying which radiological findings on the initial diagnostic CT pulmonary angiography (CTPA) for acute PE could indicate pre-existing CTEPH. The study used patients recruited for the follow-up after acute PE study (FOCUS). Index CTPA was evaluated by two independent, expert thoracic radiologists blinded to baseline characteristics, clinical outcomes and diagnosis of CTEPH during 2-year follow-up. In cases of disagreement, a third expert radiologist provided adjudicated assessment. The study included 303 patients with acute PE, with 46 patients (15.2%) classified as having chronic PE or CTEPH on index CTPA. During the follow-up, five patients (1.7%; 95% CI 0.7% to 3.8%) were diagnosed with CTEPH. An index scan classified as CTEPH conveyed significant increase in risk of a subsequent clinical diagnosis of CTEPH in follow-up (OR 24.4, 95% CI 2.7 to 223.5) compared with those without features on the index scan. However, most patients (89%) had at least one radiological parameter identified at baseline to suggest chronic thromboembolic disease on expert review with only moderate agreement between radiologists on individual features. Further work is needed to develop robust criteria that can be applied by non-specialist radiologists reliably to allow the identification of a high-risk cohort that may benefit from enhanced follow-up.
Inhaled treprostinil in pulmonary hypertension-associated interstitial lung disease: promising treatment effects
There are no proven treatments for pulmonary hypertension associated with chronic lung disease. However, inhaled prostacyclins, such as treprostinil, have shown improved functional capacity and haemodynamics in pilot studies but concerns regarding adverse impact on ventilation and perfusion matching remain. Waxman et al (N Engl J Med 2021, 384: 325) report results from the INCREASE study, a multicentre, double-blind clinical trial. The trial randomised 326 patients with interstitial lung disease and pulmonary hypertension, diagnosed on right heart catheterisation, to treprostinil (n=163) or placebo (n=163). Treprostinil was delivered via an ultrasonic nebuliser four times daily. The primary outcome, 6MWD, showed a 31.12 m difference between groups (95% CI 16.85 to 45.39; p<0.001) at 16 weeks. Time to clinical worsening was reduced (treprostinil 37/163, placebo 54/163; HR 0.61; 95% CI 0.4 to 0.92; p=0.04). However, these effects were only seen when treprostinil was continued beyond 8 weeks with a median dose of 10 breaths, four times daily and within the estimate of the minimum clinically important difference for 6MWD. There was no significant difference in the frequency of serious adverse events but there was a relatively high attrition rate in both groups of nearly 1 in 4 (treprostinil 25%, placebo 23%). The INCREASE study provides evidence to support the potential use of inhaled prostacyclin therapy in patients with pulmonary hypertension associated interstitial lung disease. However, long-term effects on functional capacity and quality of life with inhaled treprostinil requires further assessment.
Balloon pulmonary angioplasty or riociguat in patients with inoperable CTEPH? Angioplasty associated with greater physiological and clinical improvements
Optimal treatment of inoperable CTEPH remains unclear. The decision between balloon pulmonary angioplasty (BPA) and riociguat is often based on multidisciplinary opinion. Kawakami et al (Lancet Respir Med 2022;10:949) report results of a multicentre randomised trial comparing BPA and riociguat in the treatment of inoperable CTEPH at 12 months. Of 338 patients screened, 61 were randomised to BPA (n=32) or riociguat (n=29). Compared with medical therapy, BPA produced a greater reduction in pulmonary artery pressure (mean group difference −9.3 mm Hg, 95% CI −12.7 to −5.9 mm Hg; p<0.0001). At 12 months, BPA also demonstrated greater improvements in WHO functional class (p=0.0012) and reduction in home oxygen requirements (p=0.031). Interestingly, riociguat improved cardiac output (−0.8 L/min, 95% CI −1.28 to −0.33; p=0.0013), likely due to medical therapy treating microvascular lesions not amenable to BPA catheter. Although no clinical worsening or severe adverse procedure-related events were reported in the BPA group, higher rates of haemoptysis occurred (44% vs 4%). While the study provides reassurance of the clinical value of BPA, concerns regarding the generalisability of such intensive BPA procedures remains. The role of combination therapy also needs to be explored.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.