Alistair C. Church

Severe pulmonary hypertension in lung disease: phenotypes and response to treatment

Pulmonary hypertension (PH) due to lung disease (World Health Organization (WHO) group 3) is common, but severe PH, arbitrarily defined as mean pulmonary artery pressure ≥35u2005mmHg is reported in only a small proportion. Whether these should be treated as patients in WHO group 1 (i.e. pulmonary arterial hypertension) with PH-targeted therapies is unknown. We compared the phenotypic characteristics and outcomes of 118 incident patients with severe PH and lung disease with 74 idiopathic pulmonary arterial hypertension (IPAH) patients, all treated with pulmonary vasodilators. Lung disease patients were older, more hypoxaemic, and had lower gas transfer, worse New York Heart Association functional class and lower 6-min walking distance (6MWD) than IPAH patients. Poorer survival in those with lung disease was driven by the interstitial lung disease (ILD) cohort. In contrast to IPAH, where significant improvements in 6MWD and N-terminal pro-brain natruiretic peptide (NT-proBNP) occurred, PH therapy in severe PH lung disease did not lead to improvement in 6MWD or functional class, but neither was deterioration seen. NT-proBNP decreased from 2200 to 1596u2005pg·mL−1 (p=0.015). Response varied by lung disease phenotype, with poorer outcomes in patients with ILD and emphysema with preserved forced expiratory volume in 1u2005s. Further study is required to investigate whether vasodilator therapy may delay disease progression in severe PH with lung disease. Treatment of severe pulmonary hypertension associated with lung disease can improve or stabilise noninvasive outcomes http://ow.ly/Ormp1

Non‐invasive stroke volume measurement by cardiac magnetic resonance imaging and inert gas rebreathing in pulmonary hypertension

Objective:u2002 Right ventricular function determines the prognosis of pulmonary hypertension (PAH). Measurement of stroke volume (SV) non‐invasively could be a promising method to monitor disease progression. Cardiac magnetic resonance (CMR) imaging is recognized as an accurate and reproducible method to measure SV. Inert gas rebreathing (IGR) using acetylene is a validated but cumbersome method for pulmonary blood flow (PBF) measurement in PAH. A more convenient rebreathing technique using rapid photoacoustic analysis of nitrous oxide has been introduced and validated in left heart failure. We investigated the accuracy of CMR imaging and IGR using photoacoustic analysis to measure SV in patients under investigation for PAH.

Pulmonary vascular and cardiac impairment in interstitial lung disease

Pulmonary vascular and cardiac impairment is increasingly appreciated as a major adverse factor in the natural history of interstitial lung disease. This clinically orientated review focuses on the current concepts in the pathogenesis, pathophysiology and implications of the detrimental sequence of increased pulmonary vascular resistance, pre-capillary pulmonary hypertension and right heart failure in interstitial lung disease, and provides guidance on its management. Development of pulmonary hypertension is a major adverse factor in the natural history of interstitial lung disease http://ow.ly/nJB0302XAmD

Near infrared spectroscopy for the assessment of peripheral tissue oxygenation in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterised by increased pulmonary vascular resistance and results in increased morbidity and mortality due to right heart failure and a progressive decline in cardiac output [1, 2]. The latter disturbs oxygen delivery to the periphery and may lead to pathological changes in tissue oxygenation. The balance between global oxygen supply and demand is reflected in mixed venous oxygen saturation (SvO2), an index that is generally reduced in patients with PAH [3]. SvO2 at baseline is one of the strongest predictors of survival in PAH [4–6]; this is also true for changes in SvO2 during follow-up [5]. Cut-off values of 60% [7] and 65% [5] have been used to distinguish between prognostic groups suggesting that these may be suitable treatment goals. SvO2 is measured invasively in the pulmonary artery, where venous blood mixes after circulating through the superior and inferior vena cava, coronary sinuses and the right-heart chambers. Near infrared spectroscopy offers a qualitative, noninvasive indication of mixed venous oxygen saturation in PAH http://ow.ly/TSSx30231YO

The CRASH report: Emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension

Treatment of acute emergencies in patients with pulmonary arterial hypertension (PAH) can be challenging. In the UK and Ireland, management of adult patients with PAH is centred in eight nationally designated pulmonary hypertension (PH) centres. However, many patients live far from these centres and physicians in local hospitals are often required to manage PAH emergencies. A committee of physicians from nationally designated PH centres identified the ‘most common’ emergency clinical scenarios encountered in patients with PAH. Thereafter, a review of the literature was performed centred on these specified topics and a management approach was developed based on best available evidence and expert consensus. Management protocols were developed on the following PAH emergencies: chest pain (including myocardial ischaemia), right ventricular failure, arrhythmias, sepsis, haemoptysis (‘CRASH), as well as considerations relevant to surgery, anaesthesia and pregnancy. Emergencies are not uncommon in PAH. While expertise in PAH management is essential, all physicians involved in acute care should be aware of the principles of acute management of PAH emergencies. A multidisciplinary approach is necessary, with physicians from tertiary PH centres supporting care locally and planning safe transfer of patients to PH centres when appropriate.

Pulmonary hypertension in POEMS syndrome: resolution following radiotherapy

Pulmonary hypertension (PH) is defined by the presence of a mean pulmonary artery pressure (mPAP) ≥25 mmHg. It may be idiopathic or arise as a consequence of a number of diverse conditions. PH has been reported in association with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes), with reversal following systemic treatment with corticosteroids. We report a case of pulmonary hypertension associated with POEMS syndrome treated with radical radiotherapy locally to bone lesions with resolution of systemic disease.

Dynamic near-infrared spectroscopy assessment as an important tool to explore pulmonary arterial hypertension pathophysiology

We thank S. Dimopoulos and co-workers for their particular interest in our study [1] and their contributions to this issue. The peripheral muscle hypothesis in pulmonary arterial hypertension (PAH) [2] is certainly of great and growing interest due to the potential of muscle function as a target for meaningful intervention. Accordingly, our study explored the value of quadriceps muscle oxygenation profiles in patients with PAH by means of near-infrared spectroscopy (NIRS) [1]. The satisfactory correlation between vastus lateralis muscle tissue oxygenation index (StO2) and mixed venous oxygen saturation (SvO2) both at rest and during exercise support the use of NIRS in the noninvasive investigation of patients with PAH. Importantly, they suggest that skeletal muscle oxygenation profiles reflect the pathophysiology of PAH. Near-infrared spectroscopy offers a qualitative, noninvasive indication of mixed venous oxygen saturation in PAH http://ow.ly/MctV306eEYC

Validation of impedance cardiography in pulmonary arterial hypertension

Non‐invasive methods of measuring cardiac output are highly desirable in pulmonary arterial hypertension (PAH). We therefore sought to validate impedance cardiography (ICG) against thermodilution (TD) and cardiac magnetic resonance (CMR) in the measurement of cardiac output in patients under investigation for PAH.

A study of clinical and physiological relations of daily physical activity in precapillary pulmonary hypertension.

Daily physical activity is reduced in precapillary pulmonary hypertension (PH), but the underlying mechanisms are inadequately explored. We sought to investigate clinical and physiological relations of daily physical activity and profile differences between less and more active patients with precapillary PH. A prospective, cross-sectional study of 20 patients with precapillary PH who undertook 1) a comprehensive clinical assessment, 2) a preliminary treadmill test, 3) 7-day monitoring of daily walking intensity with triaxial accelerometry, and 4) a personalized treadmill test corresponding to the individual patient mean daily walking intensity with real-time physiological measurements. Significant clinical correlations with individual patient mean walking intensity [1.71 ± 0.27 (SD) m/s2] were observed for log-transformed N-terminal probrain natriuretic peptide (log NT-proBNP; r = -0.75, P = <.001), age (r = -0.70, P = 0.001), transfer factor for carbon monoxide %predicted (r = 0.51, P = 0.022), and 6-min walk distance (r = 0.50, P = 0.026). Significant physiological correlations were obtained for heart rate reserve (r = 0.68, P = 0.001), quadriceps tissue oxygenation index (Q-[Formula: see text]; r = 0.58, P = 0.008), change in Q-[Formula: see text] from rest (r = 0.60, P = 0.006), and ventilatory equivalent for oxygen uptake (r = -0.56, P = 0.013). Stepwise multiple regression analyses retained log NT-proBNP (R2 = 0.55), heart rate reserve (R2 = 0.44), and Q-[Formula: see text] (R2 = 0.13) accounting for a significant variance in individual walking intensity. Less active patients had greater physical activity-induced cardiopulmonary impairment, worse quadriceps oxygenation profile, and compromised health-related quality of life compared with more active patients. These preliminary findings suggest a significant relation between right ventricular and peripheral muscle oxygenation status and reduced daily physical activity in precapillary PH. Further research is warranted to unravel the physiological determinants, establish clinical predictors, and identify beneficial interventions.NEW & NOTEWORTHY Daily physical activity holds promise to be a meaningful, patient-related outcome measure in pulmonary hypertension. In this study, novel findings in a representative sample of patients with precapillary pulmonary hypertension link reduced daily walking activity, as measured by triaxial accelerometry, with compromised right ventricular and pulmonary vascular status, peripheral muscle oxygenation, and health-related quality of life, providing a preliminary insight into the physiological mechanisms and clinical predictors of daily physical activity in precapillary pulmonary hypertension.

S110 2-d segmental longitudinal strain rates correlate with prognostic indicators in idiopathic pulmonary arterial hypertension

Background/objectives Speckle tracking echocardiography (STE) has added to the assessment of right ventricular function by providing off-line measurements of strain and strain rate. Worsening right ventricular function is associated with poorer outcomes in idiopathic pulmonary arterial hypertension (IPAH). Global right ventricular free wall (RVFW) longitudinal strain and strain rate have been reported as markers of prognosis. Differences in degree of regional RVFW deformation will affect the global RVFW analysis. We assessed whether RVFW segmental analysis using STE identified specific regional associations with proven prognostic markers. Method Using our database, we identified newly diagnosed cases of IPAH between January 2012 and May 2016. 25 cases had echocardiograms accessible for retrospective analysis. Using 2D-STE software (EchoPAC, GE Healthcare), we measured longitudinal strain and strain rate of the RVFW basal, mid and apical segments. Data on established prognostic markers, NT-proBNP, cardiac index (CI), WHO functional class (FC), six-minute walk distance (6MWD) and mixed venous saturations (SvO2) were retrieved from the patient database. All data was anonymised for analysis. Results Basal peak systolic longitudinal strain rate (PSLSR) of the RVFW correlated very strongly with NT-proBNP (r = 0.82, p < 0.001) and moderately with CI: (r = −0.53, p < 0.007), WHO FC (r = 0.52, p < 0.008) and SvO2 (r = −0.50, p < 0.02). Basal late diastolic longitudinal strain rate (LDLSR) correlated strongly with SvO2 (r = 0.61, p < 0.002), and moderately with NT-proBNP (r = −0.58, p < 0.005), CI: (r = 0.57, p < 0.004), 6MWD (r = 0.5, p < 0.02), and WHO FC (r = −0.49, p < 0.02). Mid PSLSR and LDLSR moderately correlated with SvO2 (r = −0.53 and 0.56), NT-proBNP (r = 0.5 and −0.5) and CI (r = −0.48 and 0.42), (all p < 0.04). The apical segment showed no significant correlations. Peak systolic longitudinal strain demonstrated only one significant segmental correlation between the mid-segment and NT-proBNP (r = 0.44, p < 0.05). Abstract S110 Figure 1 Basal Late Diastolic and Peak Systolic Longitudinal Strain Rates versu Cardiac Index Conclusion We have demonstrated that analysing RVFW longitudinal segments provides significant regional correlations with known prognostic markers in an IPAH population group. We have shown the significant advantage of longitudinal strain rate over strain in its strength and consistency of correlation with these markers. We have acknowledged basal and mid segments as significant regions of interest. This study shows that further exploration of right ventricular function in pulmonary hypertension by RVFW segmental analysis is indicated.