Estimated pulmonary artery systolic pressure and sickle cell disease: a meta‐analysis and systematic review

Abstract

SummaryMany studies report estimated pulmonary artery systolic pressure (ePASP) in patients with sickle cell disease (SCD) screened by echocardiography. To better understand the prevalence and outcomes of elevated ePASP in clinically stable SCD patients, we conducted a random-effects meta-analysis. A total of 45 studies, representing 15 countries and including 6109 individuals, met our inclusion criteria. In most (70%) studies, elevated ePASP was defined by a tricuspid regurgitant velocity of 2Á5 m/s. The prevalence of elevated ePASP was 21% (17-26%) in children and 30% (26-35%) in adults. After adjustment for sex, SCD genotype, haemoglobin, hydroxycarbamide (hydroxyurea) treatment, country and publication year, age remained associated with elevated ePASP, yielding a 12% (0Á4-23%) higher adjusted prevalence in adults. Few studies reported 6-min walk tests or mortality outcomes, and estimates were highly heterogeneous. In random effects meta-analyses, patients with elevated ePASP walked an estimated 30Á4 (6Á9-53Á9) metres less than those without elevated ePASP and had an associated mortality hazard ratio of 4Á9 (2Á4-9Á7).Keywords: sickle cell disease, pulmonary hypertension, echocardiography, meta-analysis.The American Thoracic Society (ATS) recommends screening patients with sickle cell disease (SCD) every 1-3 years by echocardiography, for the detection of possible pulmonary hypertension (PHT) and increased mortality risk (Klings et al, 2014). Although right heart catheterization remains the gold standard for PHT detection, echocardiography is non-invasive and relative inexpensive, making it suitable for prospective screenings and implementation in less developed countries. To assess pulmonary artery systolic pressure (PASP) by echocardiography, the tricuspid regurgitant jet velocity (TRV) is quantified and PASP is estimated with the modified Bernoulli equation: ePASP = 4 9 (TRV) 2 + right atrial pressure (with 5 or 10 mmHg generally assumed for the right atrial pressure). Numerous echocardiography screening programmes of patients with SCD have been initiated worldwide, but to date, the prevalence and outcomes of elevated ePASP associated with SCD have not been assessed by a formal meta-analysis. Methods Literature searchPublished articles were identified using MEDLINE (PubMed) and BIOSIS (Web of Science) search engines, by entering the key term 'sickle' with 'tricuspid', 'pulmonary hypertension' or 'echocardiography'. Our initial search retrieved 757 articles published between 1964 and 2014. Reviews, duplicate citations, non-human studies, highly selected study populations and articles written in languages other than English were excluded. To avoid elevated pulmonary pressures due to vaso-occlusive pain crisis or acute chest syndrome , we omitted studies with hospitalized patients, patients presenting with cardiopulmonary symptoms and retrospective chart reviews of hospital records. We limited our analysis to steady-state prospective screenings, and publications not specifying clinically stable conditions dur...

Doppler-Defined Pulmonary Hypertension in Sickle Cell Anemia in Kurdistan, Iraq

“…Most previous studies worldwide have taken a cut-off TRV of ≥ 2.5 m/s as an indicator of pulmonary hypertension [3,14–17]. When the latter cut off point was used, nineteen of our 94 patients (20.2%) would be considered as having PH.…”

“…Among its most important pulmonary complications are acute chest syndrome (ACS) and pulmonary hypertension [2]. While most studies have used the non-invasive measurement of tricuspid regurgitant jet velocity (TRV) as an indicator of Pulmonary Hypertension (PH) with respective rates of 20–30% in sickle cell disease [3], using the invasive but "gold standard" method of right heart catheterization documented lower rates of 6.0–10.4% [4–6]. Pathogenesis of PH in sickle cell disease appears to be multifactorial, including: hemolysis induced endothelial dysfunction, chronic hypoxaemia, chronic thromboembolism, asplenia, intravascular sequestration of sickled red cells and iron overload [7].…”

Revisiting the hyperhemolysis paradigm

“…The finding that TR jet velocity is improved in the group with chronic transfusion is of significant interest as TR jet velocity is a biomarker of disease severity, associated with an increased risk of having pulmonary hypertension defined by right heart catheterization, and an independent risk factor for early death. 9,10,12 In the second study, Almeida et al report that acute intravascular hemolysis induced by hypotonic water infusion in mice produces acute NO metabolism to nitrate and acute inflammation, as measured by decreased leukocyte rolling, and increased adhesion and extravasation. Interestingly, this effect is phenocopied by acute NO inhibition using 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) and blocked by an NO donor.…”

New insights into sickle cell disease

“…These results indicate the adverse impact of pulmonary vasculopathy on the heart, and strongly suggest a relationship to exercise capacity and death. This conclusion was further supported by a new meta-analysis of pulmonary artery pressure estimated by echocardiography [15]. This meta-analysis of 45 studies totaling 6109 patients across 15 countries found higher than normal estimated pulmonary artery systolic pressure (ePASP) in 21% of children and 30% of adults with SCD.…”