Experimental Study
Right Ventricular and Pulmonary Vascular Function are Influenced by Age and Volume Expansion in Healthy Humans

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ABSTRACT

Background

Patients with heart failure (HF) often show signs of right ventricular (RV) dysfunction. The RV function of coupled with the pulmonary circulation (tricuspid annular plane systolic excursion [TAPSE]/pulmonary arterial systolic pressure [PASP]) has been shown to divide HF patients into distinct prognostic strata, but less is known about which factors influence this prognostic marker, and whether those factors can be modified. We sought to obtain normative values and discern the individual effects of age, sex, and fluid overload on RV function.

Methods and Results

Sixty healthy subjects aged 20–80 years were enrolled in this prospective study. Right heart catheterization with hemodynamic measurements were performed at rest after a rapid saline solution infusion (10 mL/kg, 150 mL/min). Linear regression and Spearman correlation models were used to estimate associations between TAPSE/PASP and relevant variables. In healthy persons of all ages, the median (5th–95th percentiles) normative TASPE-PASP ratio was 1.25 (0.81–1.78) mm/mm Hg. The correlation between progressive age and declining TAPSE/PASP was significant (r = −0.35; P = .006). Sex did not influence TAPSE/PASP (P = .30). Rapid fluid expansion increased central venous pressure from 5 ± 2 mm Hg to 11 ± 4 mm Hg after fluid infusion (P < .0001). This resulted in a 32% decrease in the TAPSE-PASP ratio after fluid infusion, compared to baseline (P < .0001).

Conclusions

The TAPSE-PASP ratio was affected by age, but not sex. TAPSE/PASP is not only a reflection of intrinsic RV function and pulmonary vascular coupling, but fluid status also dynamically affects this index of RV function. Normative values with invasive measurements were obtained for future assessment of HF patients.

Section snippets

Methods

Sixty-two healthy subjects aged 20–80 years were enrolled from the community using advertisements in this prospective two-center study, as reported previously.16 Two subjects were excluded owing to inadequate echocardiographic acoustic windows to visualize the RV, leaving 60 subjects for this study. Subjects were recruited to evenly represent sex and age when stratified into 3 decadal groups (20–39 years [n = 19], 40–59 years [n = 21], and 60–80 years [n = 20]) with relatively equal numbers of

Echocardiography

Examinations were performed with the use of a Phillips iE33 (Phillips Healthcare, Best, Netherlands) or a Vivid 9 (General Electric, Horten, Norway) ultrasound system. Measurements were made according to EACVI/ASE guidelines.17 Left ventricular volumes and LVEF were assessed by means of the Simpson modified biplane rule with the use of apical 2- and 4-chamber views. LV mass was measured by means of LV wall thickness and LV end-diastolic diameter, as described by Devereux et al.18 Maximal left

Right Heart Catheterization

Right heart catheterization was performed with the use of a standard 7.5-F triple lumen Swan-Ganz catheter (Edwards Lifesciences, Irvine, California). With the use of the Seldinger technique and guided by ultrasound, the catheter was introduced under local anesthesia into the internal jugular vein and advanced to the pulmonary artery, with the position of the catheter verified by identifying the characteristic pressure curves. Central venous pressure (CVP), systolic, diastolic, mean pulmonary

Calculations

Body surface area was estimated with the use of the Dubois formula. Pulmonary vascular resistance in Wood units was calculated as (mPAP − PCWP)/CO. Systemic vascular resistance was calculated as 80 × (MAP − CVP)/CO. Stroke volume was calculated as CO/heart rate. TAPSE/PASP was calculated with the use of echocardiographic measurements of TAPSE divided by invasive measurements of PASP.

Protocol and Saline Solution Infusion

Participants were allowed to consume their normal diet; however, participants were asked to refrain from consuming products containing caffeine. After voiding, invasive and noninvasive equipment was placed on the patient (blood pressure monitor, pulse oximeter, ECG, Swan-Ganz catheter). After resting, simultaneous invasive and echocardiographic examinations were made in the supine position with the legs resting flat (rest). After the rest measurements, isotonic saline solution was administered

Statistical Analyses

Baseline characteristics are summarized for 2 categories: participants with data available at rest (n = 60) and participants who also participated in the fluid infusion protocol (n = 50). Twenty-nine participants who underwent the saline solution infusion protocol had sufficient paired echocardiographic data (baseline + post-fluid) to assess the TAPSE-PASP relationship, whereas all 50 participants had invasive measurements available. All data were formally tested for normality with the use of

Results

Of 60 participants with satisfactory RV echocardiograhic measurements obtained for assessment of resting conditions, 50 patients (83%) were also subjected to a rapid saline solution load and had sufficient data for analysis. Baseline characteristics of both groups are summarized in Table 1.

Discussion

In this study, we prospectively enrolled healthy participants to propose normative values for TAPSE/PASP at rest and after saline solution infusion (to account for fluid loading) with the use of invasively measured PASP. In addition we show that aging—but not sex—affects this measure. The measure of TAPSE/PASP was not only a reflection of intrinsic right heart function and pulmonary vascular coupling, but it was also sensitive to acute changes in RV preload.

This information not only shows us

Study Limitations

Our main limitation lies in the low number of patients enrolled, especially those with echocardiographic measurements in the fluid infusion protocol. Of note, prospective studies in healthy individuals are limited in size historically owing to the invasive nature of the study and the ethical considerations in this context. The present study is one of the largest with healthy individuals,25, 26, 29, 30 and with even representation of participants aged 20–80 years and sexes. The limitation in

Conclusion

This is the first invasive study to quantify the impact of age and fluid on RV function coupled with pulmonary circulation without the influence of comorbidity, vasoactive medications, and possible fluid overload. In addition, we provide normative invasive values for future reference of the TAPSE-PASP ratio in the clinical evaluation of HF patients.

We found that age and fluid status were significant drivers of metrics describing RV function. With advancing age, RV function coupled with

Disclosures

None.

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