Role of cardiopulmonary exercise test in the prediction of hemodynamic impairment in patients with pulmonary arterial hypertension.

Periodic repetition of right heart catheterization (RHC) in pulmonary arterial hypertension (PAH) can be challenging. We evaluated the correlation between RHC and cardiopulmonary exercise test (CPET) aiming at CPET use as a potential noninvasive tool for hemodynamic burden evaluation. One hundred and forty-four retrospective PAH patients who had performed CPET and RHC within 2 months were enrolled. The following analyses were performed: (a) CPET parameters in hemodynamic variables tertiles; (b) position of hemodynamic parameters in the peak end-tidal carbon dioxide pressure (PETCO2) versus ventilation/carbon dioxide output (VE/VCO2) slope scatterplot, which is a specific hallmark of exercise respiratory abnormalities in PAH; (c) association between CPET and a hemodynamic burden score developed including mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and right atrial pressure. VE/VCO2 slope and peak PETCO2 significantly varied in mPAP and PVR tertiles, while peak oxygen uptake (peak VO2) and O2 pulse varied in the tertiles of all hemodynamic parameters. PETCO2 versus VE/VCO2 slope showed a strong hyperbolic relationship (R 2 = 0.7627). Patients with peak PETCO2 > median (26 mmHg) and VE/VCO2 slope < median (44) presented lower mPAP and PVR (p < 0.005) than patients with peak PETCO2 < median and VE/VCO2 slope > median. Multivariate analysis individuated peak VO2 (p = 0.0158) and peak PETCO2 (p = 0.0089) as hemodynamic score independent predictors; the formula 11.584 - 0.0925 × peak VO2 - 0.0811 × peak PETCO2 best predicts the hemodynamic score value from CPET data. A significant correlation was found between estimated and calculated scores (p < 0.0001), with a precise match for patients with mild-to-moderate hemodynamic burden (76% of cases). The results of the present study suggest that CPET could allow to estimate the hemodynamic burden in PAH patients.

Decreased pulmonary vascular distensibility in adolescents conceived by in vitro fertilization.

STUDY QUESTION: What is the functional relevance of decreased pulmonary vascular distensibility in adolescents conceived by IVF? SUMMARY ANSWER: Children born by IVF have a slight decrease in pulmonary vascular distensibility observed during normoxic exercise that is not associated with altered right ventricular function and aerobic exercise capacity. WHAT IS KNOWN ALREADY: General vascular dysfunction and increased hypoxic pulmonary hypertension have been reported in ART children as compared to controls. Pulmonary hypertension or decreased pulmonary vascular distensibility may affect right ventricular function and thereby possibly limit maximal cardiac output and aerobic exercise capacity. STUDY DESIGN, SIZE, DURATION: This prospective case-control study enrolled 15 apparently healthy adolescents conceived by IVF/ICSI after fresh embryo transfer paired in a 2 to 1 ratio to 30 naturally conceived adolescents between March 2015 and May 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifteen IVF/ICSI adolescents and 30 controls from singleton gestations matched by age, gender, weight, height and physical activity underwent exercise echocardiography, lung diffusion capacity measurements and a cycloergometer cardiopulmonary exercise test. A pulmonary vascular distensibility coefficient α was determined from the pulmonary arterial pressure (PAP) versus cardiac output (Q) relationships. Pulmonary capillary volume (Vc) was calculated from single breath nitric oxide and carbon monoxide lung diffusion capacity measurements (DLCO and DLNO) at rest and during exercise (100 W). Eight of the IVF subjects and eight controls underwent a 30 min hypoxic challenge at rest with a fraction of inspired oxygen of 0.12 to assess hypoxic pulmonary vasoconstriction. MAIN RESULTS AND THE ROLE OF CHANCE: In normoxia, oxygen uptake (VO2), blood pressure, DLCO, DLNO, echocardiographic indices of right ventricular function, Q and PAP at rest and during exercise were similar in both groups. However, IVF children had a lower pulmonary vascular distensibility coefficient α (1.2 ± 0.3 versus 1.5 ± 0.3%/mmHg, P = 0.02) and a blunted exercise-induced increase in Vc (24 versus 32%, P < 0.05). Hypoxic-induced increase in pulmonary vascular resistance in eight IVF subjects versus eight controls was similar. LIMITATIONS, REASONS FOR CAUTION: The IVF cohort was small, and thus type I or II errors could have occurred in spite of careful matching of each case with two controls. ART evolved over the years, so that it is not certain that the presently reported subtle changes will be reproducible in the future. As the study was limited to singletons born after fresh embryo transfers, our observations cannot be extrapolated to singletons born after frozen embryo transfer. WIDER IMPLICATIONS OF THE FINDINGS: The present study suggests that adolescents conceived by IVF have preserved right ventricular function and aerobic exercise capacity despite a slight alteration in pulmonary vascular distensibility as assessed by two entirely different methods, i.e. exercise echocardiography and lung diffusing capacity measurements. However, the long-term prognostic relevance of this slight decrease in pulmonary vascular distensibility needs to be evaluated in prospective large scale and long-term outcome studies. STUDY FUNDING/COMPETING INTEREST(S): Dr Caravita was supported by an ERS PAH short term research training fellowship (STRTF2014-5264). Dr Pezzuto was funded by an Italian Society of cardiology grant. Dr Motoji was supported by a grant from the Cardiac Surgery Funds, Belgium. All authors have no conflicts of interests to declare.

Unusual presentation for a patent ductus arteriosus.

A 63-yr-old black female, with a 1-yr history of hepatitis C and ascites was referred to an expert centre with suspicion of portopulmonary hypertension (PPHTN). Her poor condition made a rapid diagnosis imperative and precluded a normal diagnostic work-up. Echocardiography confirmed severe pulmonary hypertension (PH). A hepatic scintigraphy and an abdominal echo-Doppler study excluded liver cirrhosis and portal hypertension. Cardiac magnetic resonance imaging showed marked dilation of the right ventricle with significant hypertrophy of the free wall, a finding that is uncommon in idiopathic pulmonary arterial hypertension or PPHTN. Right heart catheterisation demonstrated severe pre-capillary PH without response to acute vasodilator testing. Finally the patient underwent computed tomography angiography, which showed marked dilation of the pulmonary artery without thromboembolic disease and, unexpectedly, a partially calcified large patent ductus arteriosus. The correct diagnosis of the underlying cause of pulmonary arterial hypertension is essential. Patients with underlying heart defects may have an atypical presentation and be referred to expert centres with an incorrect diagnosis. A full investigation is necessary; careful examination of right ventricular anatomy can provide clues about the aetiology of PH, and it is important to exclude intra- and extracardiac shunts during haemodynamic studies.