Ventilation-perfusion Matching During Exercise In Patients With Heart Failure With Preserved Ejection Fraction: Impact Of Phenotype

PURPOSE: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous syndrome based on central (cardiac) and/or peripheral (skeletal muscle) limitations to oxygen uptake. Patients with a central limitation may have a limited ability to increase pulmonary perfusion (cardiac output, Qc) relative to those with a peripheral limitation. This central limitation may contribute to ventilation-perfusion (V/Q) mismatch, manifesting as an increase in alveolar dead space (VDalv) and worsened ventilatory efficiency (relation between ventilation [V̇E] and carbon dioxide elimination [V̇CO2]) during exercise. To test this hypothesis, we compared Qc, VDalv and V̇E/V̇CO2 during exercise between centrally and peripherally limited HFpEF patients. METHODS: 38 subjects were categorized based on their Qc/oxygen uptake (V̇O2) slope and stroke volume (SV) reserve during a graded cycling test. Those with a Qc/V̇O2 < 5 or a Qc/V̇O2 5-6 and a SV reserve <50% were classified as having primarily a central limitation (n = 14, 70.8 ± 5.7y, 5 women). Those with a Qc/V̇O2 > 6 or a Qc/V̇O2 5-6 and a SV reserve >50% were classified as having primarily a peripheral limitation (n = 24, 70.0 ± 6.9y, 18 women). Subjects performed a 6 min constant-load cycling test (20 W). Arterial blood gases, gas exchange, and Qc (direct Fick) were measured. VDalv (Enghoff modification of the Bohr equation) and V̇E/V̇CO2 (relation between the rest-to-20 W change in V̇E and V̇CO2) were calculated. RESULTS: Qc tended to be lower (p = 0.06) in centrally (7.61 ± 1.97 L/min) compared with peripherally (8.79 ± 2.26 L/min) limited patients, whereas VDalv (central: 0.310 ± 0.07; peripheral: 0.262 ± 0.08 L/br, p = 0.01) and V̇E/V̇CO2 (central: 38.2 ± 3.4; peripheral: 35.8 ± 4.0, p = 0.03) were greater in centrally compared with peripherally limited patients during exercise. There was a strong correlation between VDalv and V̇E/V̇CO2 (r = 0.61, p < 0.01). CONCLUSIONS: Our findings suggest that V/Q mismatch worsened during exercise to a greater extent in HFpEF patients with a central limitation compared with those with a peripheral limitation. Since the increase in Qc was lower in patients with a central limitation, it could be that these patients developed a greater relative distribution of high V/Q lung units, possibly due to an impaired ability to augment pulmonary perfusion.