Right Atrial Conduit Phase Emptying Predicts Risk of Adverse Events in Pediatric Pulmonary Arterial Hypertension

doi:10.1016/j.echo.2020.02.015

Journal of the American Society of Echocardiography

Volume 33, Issue 8, August 2020, Pages 1006-1013

https://doi.org/10.1016/j.echo.2020.02.015 Get rights and content

Highlights

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Right atrial conduit phase emptying (RA cF%) is a new echo biomarker in PAH.
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RA cF% is significantly altered in pediatric PAH compared to controls.
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RA cF% is prognostic for risk of a clinical adverse event within pediatric PAH.
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RA cF% was measured in all subjects from clinical images with no special software.

Background

Idiopathic pulmonary arterial hypertension (PAH) is a severe disease associated with a 20% 5-year mortality, often due to right heart failure. Recent studies suggest that compensatory changes in right atrial (RA) function may precede other clinical and echocardiographic evidence of right ventricular dysfunction. No prior prospective study has evaluated the role of RA emptying pattern as a prognostic marker of adverse clinical events in pediatric PAH.

Objective

To demonstrate whether RA fractional emptying indices will prospectively predict risk of adverse clinical outcomes in pediatric PAH patients.

Methods

Single-center, prospective cohort analysis of 41 patients with idiopathic or heritable PAH and 1:1 age and sex-matched controls with normal echo and electrocardiogram. Right atrial area (RAA) was measured just prior to tricuspid valve opening (RAAmax), at electrical p wave (RAAp), and just after tricuspid valve closing (RAAmin). Right atrial conduit fraction percent (RA cF%) was defined as the percentage of total RAA change happening prior to the electrical p wave = (RAAmax – RAAp)/(RAAmax – RAAmin) ∗ 100. Clinical worsening was analyzed with a predefined composite adverse event outcome.

Results

RA measurements were technically feasible in all study participants. The PAH patients (median age 11.9 years) had decreased RA cF% compared with controls (P < .0001), and PAH subjects with lower RA cF% demonstrated higher right ventricular systolic (R = −0.49, P = .019) and end-diastolic (R = −0.52, P = .012) pressure than those with higher RA cF%. Sixteen subjects had a clinical event. Right atrial cF% (hazard ratio = 0.09; P < .001) was highly prognostic for risk of adverse clinical event with area under the curve = 0.90 on receiver operating characteristic curve analysis (median 3.2-year follow-up).

Conclusions

Right atrial conduit phase emptying is significantly altered in pediatric PAH. Within the PAH population, decreased RA cF% was prognostic for risk of clinical worsening. The combination of accuracy and ease of measurement could make RA cF% a clinically useful, noninvasive biomarker of early right heart failure and risk of disease progression in pediatric PAH.

Section snippets

Study Population

This study was a single-center, prospective cohort analysis of consecutive patients with known idiopathic or heritable PAH seen in the pulmonary hypertension clinic at Children's Hospital Colorado. Physicians specializing in pulmonary hypertension followed each patient clinically and confirmed the diagnosis. Subjects were enrolled at the time of their first clinical echocardiogram during the study period from January 2014 to March 2019. We did not exclude subjects based on date of diagnosis or

Study Population

Forty-two consecutive pediatric PAH patients with idiopathic or heritable pulmonary hypertension were prospectively enrolled (median age, 11.9 years; IQR, 7.8-15.6 years). No subject had a history of congenital heart disease. One study candidate was retrospectively excluded due to lack of follow-up data. Forty subjects had either no or a small interatrial communication, while one had an iatrogenic moderate-size atrial-level shunt at the time of enrollment. Thirty-six subjects had either trivial

Discussion

In this prospective study we found that (1) children with idiopathic and heritable PAH had decreased RA conduit emptying compared to age- and sex-matched controls; (2) RA cF% had a significant negative correlation with PAH severity by catheterization; (3) PAH subjects with an adverse clinical event had decreased RA cF%, larger RAA, and higher right heart pressures by catheterization compared to those without an event; and (4) decreased RA cF% and increased RVSP% were most prognostic for

Conclusion

Right atrial conduit phase emptying, as measured by noninvasive echocardiography, is significantly altered in pediatric PAH. We report the finding that PAH patients with benign clinical course have a mild decrease in conduit emptying compared with controls, while those with a severe course have worse conduit emptying. In addition, RA cF% correlates with invasive markers of disease severity and is highly prognostic for risk of a clinical adverse event within the pediatric PAH population.

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Citation Excerpt :
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Pulmonary hypertension (PH) is a progressive pulmonary vascular disorder with elevated mortality risk. The pulmonary artery (PA) pulsatility index (PAPi) based on invasively acquired parameters has emerged as a hemodynamic risk predictor. Whether noninvasively derived PAPi (PA pulse pressure divided by right atrial pressure) is valuable is unclear.
Consecutive patients undergoing transthoracic echocardiography for known or suspected PH were included with conventional echocardiographic measures of PA systolic, PA diastolic, and estimated right atrial pressures. In those patients with PH (mean PA pressure > 20 mm Hg), PAPi was divided into 3 groups: <1.5, 1.5 to 3, and >3. Mortality was assessed over 5 years.
Of 1,045 patients enrolled, 64% had PH. Patients with the lowest PAPi had higher N-terminal-pro hormone B-type natriuretic peptide levels, larger right ventricles (RVs), worse RV systolic function, and greater degrees of tricuspid regurgitation. In patients with PH, PAPi was inversely proportional to the risk of death, with PAPi <3 associated with a 1.96-fold increased risk of death (95% CI, 1.45-2.64, P < .0001). At multivariate analysis, RV longitudinal systolic strain (hazard ratio [HR] = 1.45, 1.24-1.71; P < .0001), PAPi <3 (HR = 1.76, 1.31-2.37; P = .0002), and the presence of a pericardial effusion (HR = 1.64, 1.20-2.26 P = .003) were independently associated with increased mortality. In age- and sex-adjusted models, PAPi was incremental to PA compliance.
In patients with PH, low PAPi derived noninvasively by transthoracic echocardiography is associated with markers of right heart failure, RV dysfunction, and worse survival. PAPi could be incorporated into the conventional echo parameters reported in patients with PH and may be a useful predictor of outcome.
Association of Right Ventricular Afterload With Atrial Fibrillation Risk in Older Adults: The Atherosclerosis Risk in Communities Study
2022, Chest
Atrial fibrillation (AF) is widely perceived to originate from the left atrium (LA). Whether increases in right ventricular (RV) afterload in older adults play an etiological role in AF genesis independent of LA and left ventricular (LV) remodeling is unknown.
Is higher RV afterload associated with greater AF risk independent of LA and LV remodeling?
In this observational prospective study, we included 2,246 community-dwelling older adults (mean age, 75 years) without known cardiovascular disease, with LV ejection fraction > 50%, LA volume index < 34 mL/m², and E/e’ ratio < 14 and a measurable functional tricuspid regurgitation jet velocity. From 2D-echocardiograms, we estimated pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR). We ascertained incident AF (through 2018) from hospital discharge codes and death certificates. We estimated hazard ratios (HR) by Cox regression.
During follow-up (median, 6.3 years; interquartile interval, 5.5-6.9 years), 215 participants developed AF. AF risk was significantly higher in the third (vs first) tertile of PASP (HR, 1.65; 95% CI, 1.08-2.54) and PVR (HR, 1.38; 95% CI, 1.00-2.08) independent of LA and LV structure and function, heart rate, BMI, prevalent sleep apnea, systemic BP, antihypertensive medications, and lung, kidney, and thyroid function. These associations persisted after further exclusion of participants with tricuspid regurgitation jet velocity > 2.8 m/s and lateral and septal mitral annular velocity above age- and sex-specific reference limits.
In older adults, higher RV afterload is associated with greater AF risk independent of LA and LV remodeling. Future research should focus on confirming this novel association and elucidate underlying mechanisms.
The Prognostic Value of Right Atrial Strain Imaging in Patients with Precapillary Pulmonary Hypertension
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Right ventricular (RV) failure in patients with pulmonary hypertension (PH) is associated with unfavorable clinical events and a poor prognosis. Elevation of right atrial (RA) pressure is established as a marker for RV failure. However, the additive prognostic value of RA mechanical function is unclear.
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There were 151 patients with PH (mean age, 55 ± 16 years; 73% women; mean World Health Organization functional class, 2.6 ± 0.6), after 14 exclusions (three with atrial septal defects and 11 with left ventricular ejection fractions < 50%). RA strain measurement was feasible in 93% of patients and RV strain measurement in 88%. RA peak longitudinal strain was significantly reduced in patients with PH compared with control subjects, as expected (P < .001). During 5-year follow-up, 73 patients (48%) died. Patients with RA peak strain in the lowest quartile (<25%) had a significant risk for death (P = .006), even after correcting for confounding variables. RA strain was independently associated with survival in multivariate analysis (P = .039) and had additive prognostic value to RV strain (log-rank P = .01) in subgroup analysis.
RA peak longitudinal strain had additive prognostic usefulness to other clinical measures, including RV strain, RA area, and RA pressure, in patients with PH. RA mechanical function by strain imaging has potential for clinical applications in patients with PH.
Longitudinal assessment of right atrial conduit fraction provides additional insight to predict adverse events in pediatric pulmonary hypertension
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Citation Excerpt :
In patients with diastolic dysfunction, impaired active ventricular relaxation leads to increased reliance on atrial contraction during late diastole to maintain RV preload [10]. Our findings support prior reports from prospective and retrospective cohorts in children and adults showing the value of RA cF% to predict adverse clinical events in the PAH population [6]. Although cross-sectional studies have provided evidence for the prognostic value of a variety of imaging and functional biomarkers in children with PAH, longitudinal studies to validate these metrics as potential treatment targets are limited [1,11]. [
Recent studies show adverse right atrial (RA) emptying pattern is prognostic for clinical worsening events in pediatric pulmonary arterial hypertension (PAH). No study has reported changes in RA emptying over time or evaluated whether serial measurements offer further prognostic information.
Prospective study of 32 children with idiopathic or heritable PAH undergoing echocardiogram at baseline and 1-year. RA conduit fraction percent (RA cF%) was measured as percentage of total diastolic RA area change prior to the electrical p wave. Clinical worsening was analyzed with a predefined composite adverse event outcome.
Longitudinal subjects (median age 13.3 yr) had RA cF% 61% (IQR 32–68%) at baseline and 60% (IQR 35–73%) at 1-year (NS). 11 subjects had a qualifying event during median 21-month follow-up. Subjects with an event had 1-year RA cF% = 33% (IQR 20–40%) compared to 72% (IQR 63–75%) for those with no event (p < 0.001). Event rates were lowest for subjects with both echocardiograms showing RA cF% > 60% (0%), highest for subjects with neither (80%), and intermediate for those with one (38%, p = 0.003).
Changes in RA cF% inform risk of adverse events in pediatric PAH. This finding supports the role of RA cF% as both a prognostic biomarker and potential treatment target.
Progress in the application of echocardiography in neonatal pulmonary hypertension
2024, Journal of Maternal-Fetal and Neonatal Medicine
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View all citing articles on Scopus

: Conflicts of Interest: The authors have no conflicts of interest to disclose.

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2020 by the American Society of Echocardiography.

Clinical InvestigationEchocardiography in ChildrenRight Atrial Conduit Phase Emptying Predicts Risk of Adverse Events in Pediatric Pulmonary Arterial Hypertension

Highlights

Background

Objective

Methods

Results

Conclusions

Section snippets

Study Population

Study Population

Discussion

Conclusion

Int J Cardiol

Int J Cardiol

J Am Soc Echocardiogr

Int J Cardiol

J Am Soc Echocardiogr

Int J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Diagnosis, evaluation and treatment of pulmonary arterial hypertension in children

Children

Identification of treatment goals in paediatric pulmonary arterial hypertension

Eur Respir J

Potts shunt and pediatric pulmonary hypertension: what we have learned

Ann Thorac Surg

Potts shunt improves right ventricular function and coupling with pulmonary circulation in children with suprasystemic pulmonary arterial hypertension

Circ Cardiovasc Imaging

Palliative Potts shunt for the treatment of children with drug-refractory pulmonary arterial hypertension: updated data from the first 24 patients

Eur J Cardiothoracic Surg

Use of balloon atrial septostomy in patients with advanced pulmonary arterial hypertension

Chest

Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management

Eur Respir J

Increased right atrial volume measured with cardiac magnetic resonance is associated with worse clinical outcome in patients with pre-capillary pulmonary hypertension

ESC Heart Fail

Clinical Investigation
Echocardiography in Children
Right Atrial Conduit Phase Emptying Predicts Risk of Adverse Events in Pediatric Pulmonary Arterial Hypertension