Experimental StudyRight Ventricular and Pulmonary Vascular Function are Influenced by Age and Volume Expansion in Healthy Humans
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.
References (30)
- et al.
Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study
J Am Coll Cardiol
(2009) - et al.
Physiologic correlates of tricuspid annular plane systolic excursion in 1168 healthy subjects
Int J Cardiol
(2016) - et al.
Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction
J Am Coll Cardiol
(2014) - et al.
Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings
Am J Cardiol
(1986) - et al.
Effects of healthy aging on the cardiopulmonary hemodynamic response to exercise
Am J Cardiol
(2014) - et al.
Relationships between right ventricular function, body composition, and prognosis in advanced heart failure
J Am Coll Cardiol
(2013) - et al.
Hemodynamics at rest and during supine and sitting bicycle exercise in normal subjects
Am J Cardiol
(1978) - et al.
Age-related alterations of Doppler left ventricular filling indexes in normal subjects are independent of left ventricular mass, heart rate, contractility and loading conditions
J Am Coll Cardiol
(1991) - et al.
Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction
Circ Heart Fail
(2010) - et al.
Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology
Eur J Heart Fail
(2017)
Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction
Eur. Heart J.
Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study
Circ Heart Fail
Right ventricular dysfunction as an independent predictor of short- and long-term mortality in patients with heart failure
Eur J Heart Fail
Right ventricular function in heart failure with preserved ejection fraction: a community-based study
Circulation
Impaired right ventricular–pulmonary arterial coupling and effect of sildenafil in heart failure with preserved ejection fraction: an ancillary analysis from the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX) trial
Circ Heart Fail
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