Exercise gas exchange in continuous-flow left ventricular assist device recipients

Abstract

Exercise ventilation/perfusion matching in continuous-flow left ventricular assist device recipients (LVAD) has not been studied systematically. Twenty-five LVAD and two groups of 15 reduced ejection fraction chronic heart failure (HFrEF) patients with peak VO2 matched to that of LVAD (HFrEF-matched) and ≥14 ml/kg/min (HFrEF≥14), respectively, underwent cardiopulmonary exercise testing with arterial blood gas analysis, echocardiogram and venous blood sampling for renal function evaluation. Arterial-end-tidal PCO2 difference (P(a-ET)CO2) and physiological dead space-tidal volume ratio (VD/VT) were used as descriptors of alveolar and total wasted ventilation, respectively. Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio (TAPSE/PASP) and blood urea nitrogen/creatinine ratio were calculated in all patients and used as surrogates of right ventriculo-arterial coupling and circulating effective volume, respectively. LVAD and HFrEF-matched showed no rest-to-peak change of P(a-ET)CO2 (4.5±2.4 vs. 4.3±2.2 mm Hg and 4.1±1.4 vs. 3.8±2.5 mm Hg, respectively, both p >0.40), whereas a decrease was observed in HFrEF≥14 (6.5±3.6 vs. 2.8±2.0 mm Hg, p <0.0001). Rest-to-peak changes of P(a-ET)CO2 correlated to those of VD/VT (r = 0.70, p <0.0001). Multiple regression indicated TAPSE/PASP and blood urea nitrogen/creatinine ratio as independent predictors of peak P(a-ET)CO2. LVAD exercise gas exchange is characterized by alveolar wasted ventilation, i.e. hypoperfusion of ventilated alveoli, similar to that of advanced HFrEF patients and related to surrogates of right ventriculo-arterial coupling and circulating effective volume.

Fig 1. Peak arterial-end-tidal PCO₂ difference, physiological dead space-tidal volume ratio and alveolar-arterial PO₂ difference as a function of peak VO₂ in the study population.

The prevalence of high peak P(a-ET)CO₂ and peak VD/VT values in the 3 study groups testify to a trend toward high ventilation/perfusion ratio mismatch in the whole study population. Full circles, empty triangles and full triangles are LVAD, HFrEF-matched and HFrEF≥14, respectively. P(a-ET)CO₂ = arterial-end-tidal PCO₂ difference; VD/VT = physiological dead space-tidal volume ratio; P(A-a)O₂ = alveolar-arterial PO₂ difference.

Fig 2. Schematic summarizing ventilation/perfusion pathophysiology in left ventricular assist device recipients.

The scarce left ventricular assist device preload sensitivity constrains systemic perfusion increase during exercise causing hypoperfusion of normally ventilated alveoli, which in turn leads to an increase of wasted alveolar ventilation, ventilation/perfusion ratio and VE/VCO₂ slope and to a reduction of peak VO₂. This picture might be accentuated in patients with unfavorable right ventriculo-arterial coupling caused by impaired right ventricular contractility and/or increased pulmonary pressures, low circulating effective volume due to excessive diuretic use and possibly chronotropic insufficiency and increased afterload. LVAD = left ventricular assist device.