Incident pulmonary hypertension in 13 488 cases investigated with repeat echocardiography: a clinical cohort study

Abstract

Background: We addressed the paucity of data describing the characteristics and natural history of incident pulmonary hypertension.

Methods: Adults (n=13 448) undergoing routine echocardiography without initial evidence of pulmonary hypertension (estimated right ventricular systolic pressure, eRVSP <30.0 mmHg) or left heart disease were studied. Incident pulmonary hypertension (eRVSP ≥30.0 mmHg) was detected on repeat echocardiogram a median of 4.1 years apart. Mortality was examined according to increasing eRVSP levels (30.0-39.9, 40.0-49.9 and ≥50.0 mmHg) indicative of mild-to-severe pulmonary hypertension.

Results: A total of 6169 men (45.9%, aged 61.4±16.7 years) and 7279 women (60.8±16.9 years) without evidence of pulmonary hypertension were identified (first echocardiogram). Subsequently, 5412 (40.2%) developed evidence of pulmonary hypertension, comprising 4125 (30.7%), 928 (6.9%) and 359 (2.7%) cases with an eRVSP of 30.0-39.9 mmHg, 40.0-49.9 mmHg and ≥50.0 mmHg, respectively (incidence 94.0 and 90.9 cases per 1000 men and women, respectively, per year). Median (interquartile range) eRVSP increased by +0.0 (-2.27 to +2.67) mmHg and +30.68 (+26.03 to +37.31) mmHg among those with eRVSP <30.0 mmHg versus ≥50.0 mmHg. During a median 8.1 years of follow-up, 2776 (20.6%) died from all causes. Compared to those with eRVSP <30.0 mmHg, the adjusted risk of all-cause mortality was 1.30-fold higher in 30.0-39.9 mmHg, 1.82-fold higher in 40.0-49.9 mmHg and 2.11-fold higher in ≥50.0 mmHg groups (all p<0.001).

Conclusions: New-onset pulmonary hypertension, as indicated by elevated eRVSP, is a common finding among older patients without left heart disease followed-up with echocardiography. This phenomenon is associated with an increased morality risk even among those with mildly elevated eRVSP.

FIGURE 1

Study flow chart. The study schema shows the number of potentially eligible cases who formed the study cohort once key exclusion criteria were applied, according to their estimated right ventricular systolic pressure (eRVSP) level at their last echocardiogram (last echo). NEDA: National Echo Database Australia; LHD: left heart disease; TRV: tricuspid regurgitant velocity; IQR: interquartile range. Age is presented as mean±sd. Duration of follow-up is given for each specific eRVSP group.

FIGURE 2

Change in estimated right ventricular systolic pressure (Δ eRVSP) from first to last echocardiogram (echo). The two plots show the absolute change in eRVSP according to the length of time between the first and last echo (in years) in which this difference was documented between a) 8306 cases with eRVSP <30.0 mmHg versus b) the 5412 cases who developed any grade of pulmonary hypertension (PHT) with eRVSP ≥30 mmHg. Pearson correlation coefficients are presented.

FIGURE 3

Age- and sex-specific incidence of all grades of pulmonary hypertension (PHT) according to estimated right ventricular systolic pressure (eRVSP) at last echocardiogram (echo). The horizontal bars show the sex-specific rate of de novo cases of PHT detected on last echo when adjusting for the time between first and last echo (expressed as cases per 1000 person-years follow-up) for each age group. The external figures show the actual number of de novo PHT cases used to inform each rate calculation for men and women separately relative to the size of each age group. By age group, the mean±sd ages at last echo were <30 years: 27.5±5.1 years; 30–39 years: 39.2±4.7 years; 40–49 years: 50.1±4.9 years; 50–59 years: 60.1±4.7 years; 60–69 years: 69.9±4.6 years; 70–79 years: 79.2±4.2 years; and ≥85 years: 87.1±3.6 years.

FIGURE 4

All-cause survival according to estimated right ventricular systolic pressure (eRVSP) group at last echocardiogram (echo). The curves show the age-, sex-, left heart disease and rate of change in eRVSP between echos derived from 13 448 adults in whom 2776 (20.6%) all-cause deaths were observed. The events and adjusted hazard ratios (HR) and 95% confidence intervals for each grade of the four pre-specified eRVSP groups are presented. ns: nonsignificant.

FIGURE 5

Cause of death in men and women according to estimated right ventricular systolic pressure (eRVSP) group at last echocardiogram. The bar plots show the causes of death (%) and overall mortality rate (n) according to sex (men and women) for each of the four pre-specified eRVSP groups.

FIGURE 6

Age- and sex-specific point prevalence of all grades of pulmonary hypertension (PHT) based on estimated right ventricular systolic pressure (eRVSP) on last echocardiogram (echo) at study census. The horizontal bars show the sex-specific prevalent cases of PHT at study census (expressed as case per 1000 persons) for each age group. The external figures show the actual prevalent PHT cases used to inform each rate calculation for men and women separately relative to the survival size of each age group. For each age group, the mean ages were <30 years: 26.4±2.5 years, 30–39 years: 35.0±2.8 years, 40–49 years: 45.2±2.9 years, 50–59 years: 55.5±2.9 years, 60–69 years: 65.4±2.9 years, 70–79 years: 74.9±2.8 years and ≥85 years: 85.9±4.4 years.