Validation of impedance cardiography in pulmonary arterial hypertension.

BACKGROUND: 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. METHODS: A prospective, cross-sectional study was performed to compare single-point measurements of cardiac output obtained by impedance cardiography (COICG ) technology (PhysioFlow® ) with (i) contemporaneous TD measurements (COTD ) at rest and steady-state exercise during right heart catheterization and (ii) CMR measurements (COCMR ) at rest obtained within 72 h. RESULTS: Paired COICG and COTD measurements were obtained in 25 subjects at rest and 16 subjects at exercise. COCMR measurements were obtained in 16 subjects at rest. There was unsatisfactory correlation and agreement between COICG and COTD at rest (r = 0·42, P = 0·035; bias: 1·21 l min-1 , 95% CI: -2·33 to 4·75 l min-1 ) and exercise (r = .65, P = .007; bias: 1·41 l min-1 ; 95% CI: -3·99 to 6·81 l min-1 ) and in the change in COICG and COTD from rest to exercise (r = 0·53, P = 0·033; bias: 0·76 l min-1 , 95% CI: -3·74 to 5·26 l min-1 ). There was also a lack of correlation and unsatisfactory agreement between resting COICG and COCMR (r = 0·38, P = 0·1; bias: 1·40 l min-1 , 95% CI: -2·48 to 5·28 l min-1 ). In contrast, there was close correlation and agreement between resting COTD and COCMR (r = 0·87, P<0·001; bias: -0·16 l min-1 , 95% CI: -1·97 to 1·65). CONCLUSIONS: In a representative population of patients under investigation for PAH, ICG showed insufficient qualitative and quantitative value in the measurement of resting and exercise cardiac output when compared with TD and CMR.

Short-Term Hemodynamic Effects of Apelin in Patients With Pulmonary Arterial Hypertension.

Apelin agonism causes systemic vasodilatation and increased cardiac contractility in humans, and improves pulmonary arterial hypertension (PAH) in animal models. Here, the authors examined the short-term pulmonary hemodynamic effects of systemic apelin infusion in patients with PAH. In a double-blind randomized crossover study, 19 patients with PAH received intravenous (Pyr1)apelin-13 and matched saline placebo during invasive right heart catheterization. (Pyr1)apelin-13 infusion caused a reduction in pulmonary vascular resistance and increased cardiac output. This effect was accentuated in the subgroup of patients receiving concomitant phosphodiesterase type 5 inhibition. Apelin agonism is a novel potential therapeutic target for PAH. (Effects of Apelin on the Lung Circulation in Pulmonary Hypertension; NCT01457170).

Endpoints in PAH clinical trials in the era of combination therapy: how do we decide whether something is working without going bankrupt?

There has been substantial progress in the treatment of pulmonary arterial hypertension using specific disease-targeted therapies. As the number of agents available grows, and as new treatment strategies emerge, it is essential that the endpoints we use to assess efficacy are sufficiently meaningful and sensitive enough to detect changes that are often subtle. Although the six-minute walk has been the traditional primary endpoint in clinical trials, there is now a move towards more patient-centred composite endpoints such as time to clinical worsening. These endpoints need to be more clearly defined and universally applied so as to make direct comparison between new drugs and new combinations possible.

Novel serum biomarkers in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) remains a difficult-to-treat condition with high mortality. Biomarkers are utilized to aid with diagnosis, prognostication and response to treatment. A clinically useful and PAH-specific single biomarker that is easy to measure remains elusive. This is in part due to the heterogeneity of PAH and its complex etiology. Brain natriuretic peptide and its N-terminal fragment are currently the most widely used serum markers; however, several novel serum biomarkers have been investigated recently. Taken individually, the evidence for each of these seems provisionally promising though currently weak overall. It is likely that a multibiomarker panel will be recommended in the future, with the optimal combination yet to be determined.