Acute Nitroglycerin Treatment Improves Exercise Hemodynamics, but Not Ventilation-Perfusion Matching in Patients With Heart Failure With Preserved Ejection Fraction

Introduction: Heart failure with preserved ejection fraction (HFpEF) patients exhibit a marked rise in PCWP during exercise, which may contribute to ventilation-perfusion (V/Q) mismatch and manifest as an increase in alveolar dead space (alveolar V D ) and alveolar-arterial PO 2 difference (AaPO 2 ). Nitrates reduce PCWP during exercise in HFpEF, but whether nitrates also reduce V/Q mismatch during exercise is unknown. Hypothesis: The increase in PCWP and V/Q mismatch during exercise would be attenuated with acute nitroglycerin (NTG) treatment compared with placebo in HFpEF patients. Methods: 13 patients performed a 6min cycling test at 20W and an incremental cycling test (with right-heart and arterial catheterization) with placebo and NTG treatment. The physiologic dead space to tidal volume (V D /V T ) was calculated using the Enghoff modification of the Bohr equation. Alveolar V D was calculated as: V D /V T x V T - anatomic dead space (anatomic V D , estimated as 2mL/kg lean body mass). AaPO 2 was calculated using the alveolar gas equation. Data were analyzed using a 2-way ANOVA. Results: PCWP decreased with NTG at 20W (placebo: 21.1±6.2 vs. NTG: 16.5±6.1mmHg, p=0.02) and peak exercise (placebo: 33.7±7.1 vs. NTG: 26.2±5.6mmHg, p<0.01). However, alveolar V D did not differ between treatments at rest (placebo: 0.11±0.07 vs. NTG:0.12±0.06L/breath, p=0.91), 20W (placebo: 0.22±0.09 vs. NTG: 0.24±0.10L/breath, p=0.62), or peak exercise (placebo: 0.34±0.14 vs. NTG:0.36±0.16L/breath, p=0.83). Nor did AaPO 2 differ between treatments at rest (placebo: 17.6±4.3 vs. NTG: 18.3±5.7mmHg, p=0.76), 20W (placebo: 22.0±6.9 vs. NTG: 22.1±8.1mmHg, p=0.99), or peak exercise (placebo: 25.1±9.1 vs. NTG: 27.8±9.9mmHg, p=0.41). No significant exercise-by-treatment interaction was detected for V D /V T (p=0.80). Conclusions: This study showed that NTG attenuated the increase in PCWP, but had no effect on the increase in alveolar V D or AaPO 2 during exercise. These findings suggest that the exercise-induced increase in V/Q mismatch may not be exclusively related to abnormal exercise hemodynamics. Further study is required to determine the clinical consequences and the mechanism(s) responsible for the progressive increase in V/Q mismatch during exercise in HFpEF patients.