The effect of sublingual nitroglycerin on aortic hemodynamics and exercise cardiac reserve in adults with heart failure with preserved ejection fraction

Introduction: The determinants of aortic pulse pressure (aPP) are assessed via 1) Wave separation analysis to quantify forward (Pf) and backward pressure (Pb) and 2) Reservoir-wave analysis to quantify excess (XSP) and reservoir pressure (RP). Patients with heart failure with preserved ejection fraction (HFpEF) have high arterial stiffness and present with central and peripheral arterial hypertension and a variable stroke volume (SV) response to exercise. The aim of our analysis was to acutely lower ventricular afterload (aPP and its components [RP, Pb]) during exercise with sublingual nitroglycerin (NTG) to determine whether high exercise afterload contributes to the low SV reserve during exercise in adults with HFpEF. Methods: In 34 adults with HFpEF (75% female, age: 69±6 years; BMI: 39±7 kg/m 2 ), we acquired continuous pulmonary (right-heart catheter) and arterial pressures (radial catheter) and simultaneously derived ascending aortic pressure waveforms (via SphygmoCor generalized inverse transfer function) at rest and during 6-minutes of submaximal cycling exercise (20 Watts). Participants were studied in the seated upright position during either a NTG (q15 mins, 400 μg) or placebo (PL) spray condition. We calculated stroke volume (SV) from heart rate (HR; EKG) and cardiac output ([Formula: see text]c; Direct Fick). Data were compared using two-way (condition*stage) ANOVA. Results: Aortic systolic pressure (PL: 135±23 vs NTG: 123±23 mmHg) and aPP (PL: 60±18 vs NTG: 50±18, mmHg) were lower with NTG during exercise (Condition: both, P <0.011), but the changes from rest to exercise were not different (both, Condition*Stage: P >0.290). Pf (PL: 18±6 vs NTG: 14±6 mmHg, condition: P =0.019), Pb (PL: 6±3 vs NTG: 4±2 mmHg, P <0.001) and RP (PL: 50±17 vs NTG: 39±18 mmHg, P =0.003) were lower with NTG at rest and during exercise; whereas, XSP was not different with NTG (PL: 21±7 vs NTG: 22±7 mmHg, P =0.298). The change in pulmonary artery wedge pressure (PAWP) with exercise was lower with NTG (PL: ∆13±7 vs NTG: ∆9±6 mmHg, condition*stage: P =0.024), with lower PAWP at 20 Watts only (PL: 20±9 vs NTG: 15±8 mmHg P =0.004), but the changes in HR, SV, and [Formula: see text]c were not different (all, condition*stage: P >0.566). Conclusion: NTG lowered left ventricular afterload (Pf, Pb, and RP) at rest and during exercise but there was no effect on exercise cardiac reserve in adults with HFpEF. However, the effects of NTG were not limited to changes in afterload as preload was also lower which potentially negated effects on cardiac reserve. NIH - 1P01HL137630 (BDL); AHA - 23POST1022536 (DJW). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.