Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure

Abstract

Background: Hemodynamic assessment after volume challenge has been proposed as a way to identify heart failure with preserved ejection fraction. However, the normal hemodynamic response to a volume challenge and how age and sex affect this relationship remain unknown.

Methods and results: Sixty healthy subjects underwent right heart catheterization to measure age- and sex-related normative responses of pulmonary capillary wedge pressure and mean pulmonary arterial pressure to volume loading with rapid saline infusion (100-200 mL/min). Hemodynamic responses to saline infusion in heart failure with preserved ejection fraction (n=11) were then compared with those of healthy young (<50 years of age) and older (≥50 years of age) subjects. In healthy subjects, pulmonary capillary wedge pressure increased from 10±2 to 16±3 mm Hg after ~1 L and to 20±3 mm Hg after ~2 L of saline infusion. Older women displayed a steeper increase in pulmonary capillary wedge pressure relative to volume infused (16±4 mm Hg·L(-1)·m(2)) than the other 3 groups (P≤0.019). Saline infusion resulted in a greater increase in mean pulmonary arterial pressure relative to cardiac output in women compared with men regardless of age. Subjects with heart failure with preserved ejection fraction exhibited a steeper increase in pulmonary capillary wedge pressure relative to infused volume (25±12 mm Hg·L(-1)·m(2)) than healthy young and older subjects (P≤0.005).

Conclusions: Filling pressures rise significantly with volume loading, even in healthy volunteers. Older women and patients with heart failure with preserved ejection fraction exhibit the largest increases in pulmonary capillary wedge pressure and mean pulmonary arterial pressure.

Figure 1

Protocols for experimental I and II. PCWP indicates pulmonary capillary wedge pressure; RAP, right atrial pressure; MPAP, mean pulmonary arterial pressure.

Figure 2

Changes in heart rate, SV index, MPAP, PCWP, RAP, LVTMP during rapid saline infusion. Two-way repeated measures of ANOVA with post hoc analysis were used. SV indicates stroke volume; MPAP, mean pulmonary arterial pressure; PCWP, pulmonary capillary wedge pressure; RAP, right atrial pressure; LVTMP, left ventricular transmural pressure; ●, young men; ○, older men; ▲, young women; △, older women. *P < 0.05 vs. older men, †P < 0.05 vs. young men, and ‡P < 0.05 vs. older women within same loading condition.

Figure 3

PCWP relative to saline after NS1 (upper left), and the relationship between PCWP/saline slope and age (upper right). PCWP relative to saline after NS1 (lower left), and the relationship between PCWP/saline slope and age in healthy subjects (lower right). The lower panels display indexed values. PCWP indicates pulmonary capillary wedge pressure; BSA, body surface area; ●, young men; ○, older men; ▲, young women; △, older women. *P < 0.05 vs. older women.

Figure 4

A. MPAP relative to saline after NS1 in healthy subjects (left). MPAP indicates mean pulmonary arterial pressure; BSA, body surface area; NS1, after the first set of acute saline infusion; ●, young men; ○, older men; ▲, young women; △, older women. *P < 0.05 vs. older women. B. MPAP relative to cardiac index after NS1. *P < 0.05 vs. older women, and †P < 0.05 vs. young women.

Figure 5

PCWP relative to saline in HFpEF, young subjects, and older subjects after NS1. Dashed line indicates 95% confidence limits; PCWP, pulmonary capillary wedge pressure; HFpEF, heart failure with preserved ejection fraction; NS1, after the first set of saline infusion; ●, young subjects; ○, older subjects; ■, HFpEF patients. *P < 0.05 vs. HFpEF patients.