Pulmonary Artery Occlusion Pressure May Overdiagnose Pulmonary Artery Hypertension in Sickle Cell Disease

Sharma, Sunil; Efird, Jimmy T.; Kadali, Renuka; Mehra, Sanjay; Chohan, Hadi; Liles, Darla; Gouge, Catherine A.; Boettger, Peter; Knupp, Charles

doi:10.1002/clc.22153

Cited by 12 publications

(5 citation statements)

References 30 publications

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“…A total of 45 studies (Delclaux et al , ; Kato et al , ; Akgul et al , ; Aleem et al , ; Nelson et al , ; Voskaridou et al , ; Zilberman et al , ; Aliyu et al , ; Beers et al , ; Caldas et al , ; Klings et al , ; Pashankar et al , ; Aessopos et al , ; Billy‐Brissac et al , ; Lee et al , ; Liem et al , ; Minniti et al , ; Sedrak et al , ; Colombatti et al , ; Dahoui et al , ; Johnson et al , ; Chaudry et al , ; Gordeuk et al , ; Knight‐Perry et al , ; Parent et al , ; Sachdev et al , ; Abdul‐Mohsen, ; Anjum et al , ; Blanc et al , ; Caughey et al , ; Eddine et al , ; Fonseca et al , ; Forrest et al , ; Garrido et al , ; Oguanobi et al , ; Tantawy et al , ; Cabrita et al , ; El‐Shanshory et al , ; Sharma et al , ; Agha et al , ; Cox et al , ; Dosunmu et al , ; Elmariah et al , ; Hebson et al , ; Marouf et al , ), representing 15 countries and contributing a collective population of 6109 individuals, met our inclusion criteria. Of these studies, 49% involved paediatric patients and 36% originated from non‐Western countries (Table ).…”

Section: Resultsunclassified

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

et al. 2015

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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...

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Section: Resultsunclassified

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

et al. 2015

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“…Importantly, most patients with catheter-confirmed PH were found to have PVH, which may be secondary to restrictive physiology. Recently, Sharma and colleagues showed that PCWP overestimates PAH in SCD and that the real prevalence of PVH may even be higher in SCD patients with PH(33). The typical RCM results in increased LA filling pressures, eventually causing PVH.…”

Section: Discussionmentioning

confidence: 99%

Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease

Niss¹,

Quinn²,

Lane³

et al. 2016

JACC: Cardiovascular Imaging

114

137

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Objective To identify a unifying cardiac pathophysiology that explains the cardiac pathology in SCD. Background Cardiopulmonary complications, the leading cause of adult mortality in sickle cell disease (SCD), are associated with heart chamber dilation, diastolic dysfunction, elevated tricuspid regurgitant jet velocity (TRV) and pulmonary hypertension (PH). However, no unifying cardiac pathophysiology has been identified to explain these findings. Methods In a two-part study, we first examined SCD patients who underwent screening echocardiography during steady state at our institution. We then conducted a meta-analysis of cardiac studies in SCD. Results In the 134 SCD patients studied (median age 11 years), a significant enlargement of the left atrial volume was present (z-score 3.1, P=0.002), shortening fraction (SF) was normal (37.6 ± 4.7%), and lateral and septal ratios of mitral velocity to early diastolic velocity of the mitral annulus (E/e′) were severely abnormal in 8% and 14% of patients, respectively, indicating impaired diastolic function. Both TRV and lateral E/e′ correlated with enlarged left atrial volume in SCD (P=0.003 and P=0.006, respectively). Meta-analysis of 68 studies confirmed significant left atrial diameter enlargement in SCD patients compared to controls, evidence of diastolic dysfunction and enlarged left ventricular end-diastolic dimension with normal SF. The majority of patients with catheter-confirmed PH had mild pulmonary venous hypertension consistent with restrictive cardiac physiology. Conclusions Patients with SCD have a unique cardiomyopathy with restrictive physiology that is superimposed on hyperdynamic physiology, and is characterized by diastolic dysfunction, left atrial dilation and normal systolic function. This results in mild, secondary, pulmonary venous hypertension and elevated TRV. Sudden death is common in other forms of restrictive cardiomyopathy. Our finding of this unique restrictive cardiomyopathy may explain the increased mortality and sudden death seen in patients with SCD with mildly elevated TRV.

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“…TRV elevation ≥2.5 m/s has sensitivity and specificity of 78% and 19%, respectively, for pulmonary hypertension, which has reproducibly been associated with increased mortality among adults with sickle cell disease (SCD) . In SCD, pulmonary hypertension may be secondary to pulmonary arterial or venous hypertension . Although not fully defined, this prognostic role of TRV elevation in SCD appears to correlate with disease severity, as demonstrated by studies linking TRV elevation and increased frequency of vaso‐occlusive pain, acute chest syndrome episodes, and proteinuria .…”

Section: Introductionmentioning

confidence: 99%

Elevated tricuspid regurgitation velocity in congenital hemolytic anemias: Prevalence and laboratory correlates

Yates

Joshi

Aygün

et al. 2019

Pediatric Blood & Cancer

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Elevated tricuspid valve regurgitation jet velocity (TRV ≥ 2.5 m/s) is associated with mortality among adults with sickle cell disease (SCD), but correlative biomarkers are not studied according to treatment exposure or genotypes. To investigate the associations between biomarkers and TRV elevation, we examined the relationship between TRV and hemolytic, inflammatory, and cardiac biomarkers, stratified by disease‐modifying treatments and SCD genotype. In total, 294 participants with SCD (mean age, 11.0 ± 3.7 years) and 49 hereditary spherocytosis (HS; mean age, 22.9 ± 19.75 years) were included for comparison and enrolled. TRV was elevated in 30.7% of children with SCD overall: 18.8% in HbSC/HbSβ+‐thalassemia, 28.9% in untreated HbSS/HbSβ0‐thalassemia, 34.2% in HbSS/HbSβ0‐thalassemia hydroxyurea‐treated, and 57% in HbSS/HbSβ0‐thalassemia chronic transfusion treated. TRV was elevated in 10.7% and 27.8% in HS children and adults, respectively. In children with SCD, elevated TRV was correlated with hemoglobin (odds ratio [OR] = 0.78, P = 0.004), lactate dehydrogenase (LDH; OR = 2.52, P = 0.005), and N‐terminal pro‐brain natriuretic peptide (NT‐pro BNP; OR = 1.003, P = 0.004). In multivariable logistic regression, adjusting for genotype, sex, hemolytic index, and treatment, hemoglobin concentration remained the only significant variable associated with elevated TRV in untreated HbSS/HbSβ0‐thalassemia participants. TRV was not associated with inflammatory markers, other markers of hemolysis, or NT‐pro BNP in untreated HbSS/HbSβ0‐thalassemia. Neither hemoglobin nor LDH was associated with TRV in HbSC/HbSβ+‐thalassemia. These results suggest that elevated TRV is influenced by the degree of anemia, possibly reflecting sickling as part of the disease pathophysiology. Prospective studies should monitor hemoglobin concentration as children with SCD age into adulthood, prompting initiation of TRV screening and monitoring.

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Pulmonary Artery Occlusion Pressure May Overdiagnose Pulmonary Artery Hypertension in Sickle Cell Disease

Cited by 12 publications

References 30 publications

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

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

Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease

Elevated tricuspid regurgitation velocity in congenital hemolytic anemias: Prevalence and laboratory correlates

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