The challenge of an expanded therapeutic window in pulmonary hypertension

Our understanding of the causes and consequences of pulmonary hypertension is limited. Consequently, its most distinctive forms with the worst prognosis have been the focus for diagnosis and treatment. We highlight the emerging challenge of reframing the prevalence and prognostic implications of pulmonary hypertension, focusing on the optimal therapeutic window to address the high mortality linked to this condition

Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography

Objective We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS). Methods Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category. Results 49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS—comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged \u3c30 years vs \u3e80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p\u3c0.001). Conclusions New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance

Mild pulmonary hypertension and premature mortality among 154 956 men and women undergoing routine echocardiography

Background Although mild pulmonary hypertension is known to be associated with increased mortality, its impact on premature mortality is largely unknown. Methods We studied the distribution of estimated right ventricular systolic pressure (eRVSP) among a total of 154 956 adults with no evidence of left heart disease investigated with echocardiography. We then examined individually linked mortality, premature mortality and associated life-years lost (LYL) according to eRVSP levels. Results The cohort comprised 70 826 men and 84 130 women (aged 61.3±17.7 and 61.4±18.4 years, respectively). Overall, 85 173 (55.0%), 49 276 (31.8%), 13 060 (8.4%) and 7447 (4.8%) cases had eRVSP levels indicative of no (<30.0 mmHg), mild (30.0–39.9 mmHg), moderate (40.0–49.9 mmHg) or severe (≥50.0 mmHg) pulmonary hypertension, respectively. During a median (interquartile range) 5.7 (3.2–8.9) years of follow-up, 38 456/154 986 (24.8%) individuals died. Compared with eRVSP <30.0 mmHg, age and sex-adjusted hazard ratios for all-cause and cardiovascular-related mortality were 1.90 (95% CI 1.84–1.96) and 1.85 (95% CI 1.74–1.97), respectively, for eRVSP 35.0–39.9 mmHg. Overall, 6256 (54%) men and 7524 (55%) women died prematurely. As a proportion of all deaths, premature mortality rose from 46.7% to 79.2% among those with eRVSP <30.0 versus ≥60.0 mmHg with a mean of 5.1–11.4 LYL each time. However, due to more individuals affected overall, eRVSP 30.0–39.9 mmHg accounted for 58% and 53% of total LYL among men (40 606/70 019 LYL) and women (47 333/88 568 LYL), respectively. Conclusions These data confirm that elevated eRVSP levels indicative of mild pulmonary hypertension are associated with increased risk of death. Moreover, this results in a substantive component of premature mortality/LYL that requires more proactive clinical surveillance and management

Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography

Objective We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS). Methods Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category. Results 49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS—comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged 80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p<0.001). Conclusions New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance

Integrated care and optimal management of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) may occur as an idiopathic process or as a component of a variety of diseases, including connective tissue diseases, congenital heart disease, and exposure to appetite suppressants or infectious agents such as HIV. Untreated, it is a potentially devastating disease; however, diagnosis can be difficult due to the non-specific nature of symptoms during the early stages, and the fact that patients often present to a range of different medical specialties. The past decade has seen remarkable improvements in our understanding of the pathology associated with the condition and the development of PAH-specific therapies with the ability to alter the natural history of the disease. This article reviews the evidence for screening and diagnosis of susceptible patient groups and discusses treatment selection and recommendations based on data available from randomized controlled trials. In addition, due to the complexity of the diagnostic evaluation required and the treatment options available, this review mandates for a multidisciplinary approach to the management of PAH. We discuss the roles and organizational structure of a specialized PAH center in Perth, Western Australia to highlight these issues

Incident pulmonary hypertension in 13488 cases investigated with repeat echocardiography : A clinical cohort study

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

Ejection fraction and mortality: A nationwide register-based cohort study of 499 153 women and men

Aims: We investigated the sex-based risk of mortality across the spectrum of left ventricular ejection fraction (LVEF) in a large cohort of patients in Australia. Methods and results: Quantified levels of LVEF from 237 046 women (48.1%) and 256 109 men undergoing first-time, routine echocardiography (2000–2019) were linked to 119 232 deaths (median 5.6 years of follow-up). Overall, 17.6% of men vs. 8.3% of women had an LVEF P\u3c 0.001] in women and 1.21 (95% CI 1.05–1.39; P = 0.008) in men. In women, an LVEF of 60.0–64.9% was also associated with a HR 1.33 (95% CI 1.16–1.52; P\u3c 0.001) for cardiovascular-related mortality. These associations were most striking in women and men aged Conclusions: Among patients investigated for suspected or established cardiovascular disease, we found clinically relevant sex-based differences in the distribution and mortality associated with an LVE

Prevalence of pulmonary hypertension in mitral regurgitation and its influence on outcomes

Objective: Pulmonary hypertension (PHT) commonly coexists with significant mitral regurgitation (MR), but its prevalence and prognostic importance have not been well characterised. In a large cohort of adults with moderate or greater MR, we aimed to describe the prevalence and severity of PHT and assess its influence on outcomes. Methods: In this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction &gt;50% and with moderate or greater MR were included (n=9683). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes was evaluated (median follow-up of 3.2 years, IQR 1.3–6.2 years). Results: Subjects were aged 76±12 years, and 62.6% (6038) were women. Overall, 959 (9.9%) had no PHT, and 2952 (30.5%), 3167 (32.7%), 1588 (16.4%) and 1017 (10.5%) patients had borderline, mild, moderate and severe PHT, respectively. A ‘typical left heart disease’ phenotype was identified with worsening PHT, showing rising E:e′, right and left atrial sizes increasing progressively, from no PHT to severe PHT (p&lt;0.0001, for all). With increasing PHT severity, 1- and 5-year actuarial mortality increased from 8.5% and 33.0% to 39.7% and 79.8%, respectively (p&lt;0.0001). Similarly, adjusted survival analysis showed the risk of long-term mortality progressively increased with higher eRVSP levels (adjusted HR 1.20–2.86, borderline to severe PHT, p&lt;0.0001 for all). A mortality inflection was apparent at an eRVSP level &gt;34.00 mm Hg (HR 1.27, CI 1.00–1.36). Conclusions: In this large study, we report on the importance of PHT in patients with MR. Mortality increases as PHT becomes more severe from an eRVSP of 34 mm Hg onwards