Right heart adaptation during exercise in pulmonary arterial hypertension and in pulmonary hypertension due to heart failure with preserved ejection fraction

Abstract Background Right heart failure (RHF) represents the final step of distinct diseases, such as pulmonary arterial hypertension (PAH) and pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (HFpEF). RHF may be defined by the inability of the heart to maintain a normal cardiac output (CO) or to do so at the expense of high right atrial pressure (RAP), at rest or during exercise. However, exercise hemodynamic features suggestive of RHF, as well as their determinants, have still not been defined. Aim We sought to i. define the limits of normal of RAP increase during exercise; ii. describe the behavior of RAP during exercise in PAH and in PH-HFpEF, and its relation to right heart afterload and preload. Methods We retrospectively analyzed data from consecutive patients referred for suspicion of PH, who underwent both a resting and exercise right heart catheterization at two centers with identical methodology. We included patients with PH-HFpEF or PAH. Right heart adaptation to exercise was described either using absolute or CO-normalized RAP increase during exercise (RAP/CO slope), this latter representing the inverse of the Frank-Starling reserve. A control cohort of subjects with normal hemodynamics at rest and during exercise served to define abnormal increase in RAP, i.e. values of RAP and RAP/CO slope > mean ± 2 standard deviation of controls. Estimated stressed blood volume (eSBV), as a measure of effective preload, was computed using a commercially-available software. Results 80 patients were included in the analysis, of which 29 were PH-HFpEF, 30 PAH and 21 controls. HFpEF patients were older than PAH patients and with a higher burden of cardiovascular comorbidities (p<0.05). Sex representation, BMI, and NTproBNP values were similar in the two groups. Mean pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) and total vascular resistance (TPR) were higher in PAH than in PH-HFpEF both at rest and during exercise (p<0.01), in spite of similar CO (Table 1). At rest, eSBV did not differ between HFpEF and PAH, but it was higher in HFpEF at peak exercise. On average, PH-HFpEF had higher resting and peak RAP than PAH, as well as higher RAP/CO slope (Figure 1). The upper limit of normal of exercise RAP and of RAP/CO slope, as determined in control subject, was 12 mmHg and 1.55 mmHg/L/min. A higher rate of HFpEF patients, compared with PAH, had a RAP/CO slope and a peak RAP above normal limits (78% and 91% of PH-HFpEF vs 47% and 44% of PAH, respectively, p<0.001). RAP/CO slope in the whole cohort was associated with eSBV but not with right ventricular afterload measures (PAP, TPR, PVR). Conclusions PH-HFpEF display more frequently a steeper increase of RAP during exercise than PAH patients in spite of similar CO, suggesting a more exhausted Frank-Starling reserve. The steep RAP increase during exercise seems to reflect a dysfunctional preload rather than an afterload-mismatch. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.