Reactivity of pulmonary circulation and right ventricle function to inhaled nitric oxide in systemic sclerosis patients.

Systemic sclerosis (SSc) is complicated by pulmonary hypertension and right ventricle (RV) failure in approximately 10% of the patients. Factors influencing the reactivity of pulmonary circulation to vasodilators are not established, while the examination of vasoreactivity is important in determining the treatment, because systemic administration of oral vasodilators can induce severe adverse events in nonresponders. The mechanism of RV failure in SSc is unclear and may result either from increased RV afterload or intrinsic myocardial disease. The aim of the study was to assess the reactivity of pulmonary circulation to inhaled nitric oxide (iNO) and to evaluate its influence on RV function in SSc patients with elevated right ventricle systolic pressure (RVSP). In 60 SSc patients aged 24-73 (58 females, two males; 33 patients with limited SSc and 27 with diffuse SSc), echocardiographic examination with tissue Doppler echocardiography (TDE) was performed. RV function was measured by systolic (S) and early diastolic (E) velocity of tricuspid annulus by TDE. In patients with RVSP >45 mmHg, the reactivity of pulmonary circulation was assessed by iNO test. High-resolution computerized tomography (HRCT) was performed to assess the extent of pulmonary fibrosis. Of 14 SSc subjects with elevated RVSP (13 females, one male; RVSP 47-62 mmHg), positive reaction to iNO was observed in five (RVSP decreased from 51.6 ± 3.7 to 32.24 ± 2.3 mmHg); nine patients were not reactive (RVSP 53.5 ± 5.7 mmHg before iNO vs. 49.6 ± 6.7 mmHg). RV systolic function was decreased in patients with elevated RVSP as compared to the patients with normal pulmonary pressure (S velocity 13.2 ± 1.3 vs. 14.4 ± 1.6 cm/s, respectively, p < 0.05). Significant increase of RV systolic function during iNO test was found in reactive patients only (S velocity before iNO 12.8 ± 1.2 cm/s, during iNO 14.5 ± 1.5 cm/s, p < 0.01). RVSP decrease strongly correlated with S velocity increase (r = 0.95, p < 0.0001). Response to iNO was found only in limited form of SSc; diffuse SSc patients showed no response. Pulmonary fibrosis on HRCT was more frequent in subjects nonreactive to iNO (67% of patients) than in the reactive group (40% of patients). The reactivity of pulmonary circulation to iNO in SSc patients with elevated RVSP was found predominantly in limited form of the disease. Pulmonary fibrosis typical for diffuse SSc was more frequent in nonreactive subjects. Elevated pulmonary pressure plays an important role in RV systolic dysfunction. Pulmonary pressure decrease during iNO test leads to the improvement of RV systolic function. Therapy for right-heart failure in reactive SSc patients should be directed, if possible, at the decrease in pulmonary resistance.

Diastolic heart dysfunction, increased pulmonary capillary wedge pressure and impaired exercise tolerance in patients with systemic sclerosis.

BACKGROUND: Diastolic heart dysfunction, responsible for dyspnoea in heart failure patients, is an important prognostic factor. Patients with systemic sclerosis (SSc) serve as a model of diastolic heart failure with preserved ejection fraction. AIM: To quantify diastolic left ventricular (LV) dysfunction and elevation of pulmonary capillary wedge pressures (PCWP) in SSc patients and to assess the effects of these parameters on exercise tolerance. METHODS: In 46 SSc patients (43 females, three males, aged 24-73 years) and 30 healthy females, echocardiography with tissue Doppler (TDE) and cardiopulmonary exercise tests (CPX) were performed. During TDE, the systolic (S) and early diastolic (E) velocities of mitral annulus were recorded. The PCWP was calculated on the basis of mitral inflow E velocity and E velocity of mitral annulus. The CPX was performed using a modified Bruce protocol. RESULTS: Left ventricular ejection fraction was normal in the SSc group. Mitral inflow E/A ratio was pseudonormal in five SSc patients, and significantly decreased in the remainder as compared to controls (0.87 ± 0.2 vs 1.38 ± 0.5, p < 0.0002). The TDE examination confirmed normal systolic LV function, but severe LV diastolic dysfunction (E 8.66 ± 2.5 cm/s vs 12.39 ± 3.5 cm/s in controls, p < 0.000002). The PCWP was higher in the SSc group (11.8 ± 3.3 mm Hg vs 7.7 ± 1.7 mm Hg in controls, p < 0.0001). The PCWP > 10 mm Hg significantly decreased exercise duration, maximal oxygen uptake and carbon dioxide output and identified patients with oxygen uptake < 20 mL/kg/min with 100% sensitivity and 78% specificity. The ventilatory equivalent of carbon dioxide was increased in the SSc group (VE/VCO2 38.7 ± 7.5 vs 30.55 ± 4.2 in controls, p < 0.002). CONCLUSIONS: Pure LV diastolic dysfunction, typical of SSc, leads to the elevation of PCWP. Values of PCWP > 10 mm Hg are associated with severe exercise intolerance demonstrated by shorter duration of exercise with decreased oxygen uptake and carbon dioxide output during exercise.