Adriana Pavelescu

Isolated right ventricular dysfunction in systemic sclerosis: latent pulmonary hypertension?

Right ventricular function is frequently abnormal in patients with systemic sclerosis, but whether this is related to pulmonary vascular complications of the disease is unclear. Standard echocardiography with tissue Doppler imaging was performed at rest and during exercise for the study of right ventricular function and pulmonary circulation in 25 consecutive systemic sclerosis patients and in 13 age-matched healthy controls. When compared with the controls, the patients had no difference in systolic right ventricular pressure gradient, but a decreased pulmonary flow acceleration time, and increased right ventricular free wall thickness and end-diastolic dimensions. At the tricuspid annulus, the E maximal velocity was decreased (8.9±4 versus 11.7±2.3 cm·s−1) and the isovolumic relaxation time corrected to RR interval was increased (6.5±2.9 versus 4.5±2.5%). The tissue Doppler imaging profile at the mitral annulus was similar in both groups. At exercise, 18 patients had a decreased maximum workload and cardiac output, no change in systolic right ventricular pressure gradient, but an increase in the slope of pulmonary artery pressure/flow relationships. These results suggest that patients with systemic sclerosis may present with latent pulmonary hypertension as a likely cause of right ventricular diastolic dysfunction, as revealed by stress echocardiography and tissue Doppler imaging.

Pulmonary circulation and gas exchange at exercise in Sherpas at high altitude

Tibetans have been reported to present with a unique phenotypic adaptation to high altitude characterized by higher resting ventilation and arterial oxygen saturation, no excessive polycythemia, and lower pulmonary arterial pressures (Ppa) compared with other high-altitude populations. How this affects exercise capacity is not exactly known. We measured aerobic exercise capacity during an incremental cardiopulmonary exercise test, lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) at rest, and mean Ppa (mPpa) and cardiac output by echocardiography at rest and at exercise in 13 Sherpas and in 13 acclimatized lowlander controls at the altitude of 5,050 m in Nepal. In Sherpas vs. lowlanders, arterial oxygen saturation was 86 ± 1 vs. 83 ± 2% (mean ± SE; P = nonsignificant), mPpa at rest 19 ± 1 vs. 23 ± 1 mmHg (P < 0.05), DL(CO) corrected for hemoglobin 61 ± 4 vs. 37 ± 2 ml · min(-1) · mmHg(-1) (P < 0.001), DL(NO) 226 ± 18 vs. 153 ± 9 ml · min(-1) · mmHg(-1) (P < 0.001), maximum oxygen uptake 32 ± 3 vs. 28 ± 1 ml · kg(-1) · min(-1) (P = nonsignificant), and ventilatory equivalent for carbon dioxide at anaerobic threshold 40 ± 2 vs. 48 ± 2 (P < 0.001). Maximum oxygen uptake was correlated directly to DL(CO) and inversely to the slope of mPpa-cardiac index relationships in both Sherpas and acclimatized lowlanders. We conclude that Sherpas compared with acclimatized lowlanders have an unremarkable aerobic exercise capacity, but with less pronounced pulmonary hypertension, lower ventilatory responses, and higher lung diffusing capacity.

Pulmonary Vascular Reserve and Exercise Capacity at Sea Level and at High Altitude

It has been suggested that increased pulmonary vascular reserve, as defined by reduced pulmonary vascular resistance (PVR) and increased pulmonary transit of agitated contrast measured by echocardiography, might be associated with increased exercise capacity. Thus, at altitude, where PVR is increased because of hypoxic vasoconstriction, a reduced pulmonary vascular reserve could contribute to reduced exercise capacity. Furthermore, a lower PVR could be associated with higher capillary blood volume and an increased lung diffusing capacity. We reviewed echocardiographic estimates of PVR and measurements of lung diffusing capacity for nitric oxide (DL(NO)) and for carbon monoxide (DL(CO)) at rest, and incremental cardiopulmonary exercise tests in 64 healthy subjects at sea level and during 4 different medical expeditions at altitudes around 5000 m. Altitude exposure was associated with a decrease in maximum oxygen uptake (VO2max), from 42±10 to 32±8 mL/min/kg and increases in PVR, ventilatory equivalents for CO2 (V(E)/VCO2), DL(NO), and DL(CO). By univariate linear regression VO2max at sea level and at altitude was associated with V(E)/VCO2 (p<0.001), mean pulmonary artery pressure (mPpa, p<0.05), stroke volume index (SVI, p<0.05), DL(NO) (p<0.02), and DL(CO) (p=0.05). By multivariable analysis, VO2max at sea level and at altitude was associated with V(E)/VCO2, mPpa, SVI, and DL(NO). The multivariable analysis also showed that the altitude-related decrease in VO2max was associated with increased PVR and V(E)/VCO2. These results suggest that pulmonary vascular reserve, defined by a combination of decreased PVR and increased DL(NO), allows for superior aerobic exercise capacity at a lower ventilatory cost, at sea level and at high altitude.

Echocardiography of pulmonary vascular function in asymptomatic carriers of BMPR2 mutations.

To the Editors: Pulmonary arterial hypertension (PAH) is a rare, life-threatening dyspnoea–fatigue syndrome, caused by progressive increase in pulmonary vascular resistance (PVR) and eventual right ventricular failure [1]. The heritable form of PAH has been shown to be associated with mutations of the gene encoding the bone morphogenetic protein receptor-2 ( BMPR2 ). Asymptomatic carriers of BMPR2 mutations are at high risk of developing PAH [2]. Careful follow-up of these subjects might help to detect early-stage disease with a more favourable response to targeted therapies. However, there is uncertainty about the optimal screening method. A recent European multicentre study showed that relatives of patients with idiopathic PAH (IPAH) present with an increased prevalence of abnormally high pulmonary artery pressure (PAP) during exercise or during low-oxygen breathing [3]. In that study, measurements of pulmonary vascular function were limited to a systolic PAP (sPAP) estimated from the maximum tricuspid regurgitation velocity (TRV) assessed by Doppler echocardiography. Here, we report on additional measurements performed in one of the participating centres, providing insight into abnormal pulmonary vascular distensibility and hypoxia-induced PVR in healthy BMPR2 carriers. This study was part of a larger multicentre European project, which included 291 relatives of 109 IPAH patients and 191 age-matched controls [3]. The participating PAH centre in Brussels, Belgium, contributed with 35 relatives of 10 index patients with IPAH and 38 healthy controls. The 35 relatives were aged mean±sd 35±14 yrs. The 38 controls were aged mean±sd 36±10 yrs, and matched for sex and body surface area. Five of the asymptomatic relatives and two of the index IPAH patients were carriers …

A simple echocardiographic score for the diagnosis of pulmonary vascular disease in heart failure

Aims A simple echocardiographic score was designed for diagnosing precapillary vs postcapillary pulmonary hypertension and for discriminating between isolated postcapillary pulmonary hypertension (Ipc-PH) and combined precapillary and postcapillary pulmonary hypertension (Cpc-PH). Methods The score comprised 7 points (2 for E/e′ ratio ⩽10, 2 for a dilated non-collapsible inferior vena cava, 1 for a left ventricular eccentricity index ≥1.2, 1 for a right-to-left heart chamber dimension ratio >1 and 1 for the right ventricle forming the heart apex) and was applied to 230 consecutive patients referred for evaluation of pulmonary hypertension. Results Precapillary pulmonary hypertension and postcapillary pulmonary hypertension were diagnosed in 160 and 70 patients, respectively. In the latter, Ipc-PH was found in 51 and Cpc-PH in 19. The echo score was higher in precapillary vs postcapillary pulmonary hypertension patients (4.2 ± 1.7 vs 1.6 ± 1.7, P < 0.001) and in patients with Cpc-PH vs Ipc-PH (2.7 ± 2.1 vs 1.2 ± 1.3, P = 0.001). The sensitivity and specificity of the echo score at least 2 for precapillary pulmonary hypertension were 99 and 54%, respectively (area under the curve 0.85). In patients with postcapillary pulmonary hypertension, the sensitivity and specificity of the echo score at least 2 for Cpc-PH were 63 and 82% (area under the curve 0.73). Conclusion A simple echocardiographic score helps in the differential diagnosis between precapillary and postcapillary pulmonary hypertension, and between Ipc-PH and Cpc-PH.