Tricuspid Regurgitant Jet Research Articles

The global burden of pulmonary hypertension in sickle cell disease: a systematic review and meta-analysis.

Elevated tricuspid regurgitant jet velocity (TRJV) is a surrogate measure of pulmonary hypertension (PH) in persons with sickle cell disease (SCD). We sought to estimate the burden of PH in people living with sickle cell disease based on TRJV. From 2000 to 2015, we searched electronic databases for eligible publications and included 29 studies (n = 5358 persons). We used random effects modeling to determine the pooled estimate of elevated TRJV. The overall pooled prevalence of elevated TRJV was 23.5%(95% CI 19.5-27.4) in persons with SCD. The pooled prevalence of elevated TRJV in children and adults with SCD was 20.7% (95% CI 15.7--25.6) and 24.4% (95% CI 18.4-30.4), respectively. TRJV is prevalent among adults and children with SCD. Our finding support international recommendations that call for screening for PH in SCD patients.

31 Pulmonary hypertension in severe aortic stenosis: prevalence and reversibility with transcatheter aortic valve implant

Introduction We explored the impact of transcatheter aortic valve implantation (TAVI) on pulmonary hypertension (PH) by assessing the prevalence and reversibility of PH in an unselected TAVI cohort. We also identified factors that may predict PH and regression of PH after TAVI. Methods Retrospective analysis of a local TAVI database. 308 consecutive patients underwent TAVI between 2008–13. Pulmonary artery systolic pressure (PASP) was estimated from the velocity of tricuspid regurgitation jet using Bernouille principle; PH was diagnosed if PASP was ≥50mmHg. Simple correlation (Spearman’s rank rS) and regression analyses were used to determine predictors of PH and the change (and 95% confidence interval) in PASP (ΔPASP) after TAVI. Wilcoxon signed-rank Z-test was used to analyse ordinal data. Results 71 (23%) patients had PH, in this group mean PASP before TAVI was 62 ± 6.5mmHg. PASP reduced in 56%, the mean ΔPASP was -12.8mmHg (95% C. I. -9.5 to -16.1, P Conclusion PH is common and usually reversible post TAVI. MR is a significant predictor of PH, the only predictor of regression of PH is reduction in LV end-diastolic function at implantation.

Caesarean section in Eisenmenger’s syndrome: anaesthetic management with titrated epidural and nebulised alprostadil

Pregnancy in patients with Eisenmenger’s syndrome is associated with a high mortality. This article reports two cases of women with Eisenmenger’s syndrome (secondary to two different primary cardiac defects) who presented with near-term pregnancies. Both the patients underwent successful elective Caesarean section with slowly titrated epidural anaesthesia. Nebulised prostaglandin E1(PGE1) analogue, alprostadil, administered immediately post-delivery resulted in a significant drop in systolic pulmonary artery pressures as measured from tricuspid regurgitant jet by transthoracic echocardiography. The postoperative period was uneventful in both patients. A slow induction of epidural anaesthesia can be a safe mode of anaesthesia for Caesarean section in pregnant patients with Eisenmenger’s syndrome. Nebulised alprostadil intraoperatively or postoperatively in the intensive care unit (ICU) is readily available and a relatively cheap option as a selective pulmonary vasodilator in developing countries.

Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease

ObjectivesThe aim of this study was to identify a unifying cardiac pathophysiology that explains the cardiac pathological features in sickle cell disease (SCD). BackgroundCardiopulmonary complications, the leading cause of adult death in SCD, are associated with heart chamber dilation, diastolic dysfunction, elevated tricuspid regurgitant jet velocity (TRV), and pulmonary hypertension. However, no unifying cardiac pathophysiology has been identified to explain these findings. MethodsIn a 2-part study, we first examined patients with SCD who underwent screening echocardiography during steady state at our institution. We then conducted a meta-analysis of cardiac studies in SCD. ResultsIn the 134 patients with SCD studied (median age 11 years), significant enlargement of the left atrial volume was present (z-score 3.1, p = 0.002), shortening fraction 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 patients with SCD compared with controls, evidence of diastolic dysfunction and enlarged left ventricular end-diastolic dimension with normal shortening fraction. The majority of patients with catheter-confirmed pulmonary hypertension had mild pulmonary venous hypertension consistent with restrictive cardiac physiology. ConclusionsPatients with SCD have a unique form of cardiomyopathy with restrictive physiology that is superimposed on hyperdynamic physiology and is characterized by diastolic dysfunction, left atrial dilation, and normal systolic function. This combination 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 rates and sudden death seen in patients with SCD with mildly elevated TRV.

Restoration of Tricuspid Valve Mechanism at the Level of Displaced Septal and Posterior Leaflets in Ebstein's Anomaly.

Surgical techniques currently used for the repair of Ebstein's anomaly comprise reconstruction of the tricuspid valve mechanism at the level of the true annulus with or without plication of the atrialized right ventricle. However, performing this procedure for patients with a dysmorphic anterior leaflet (i.e., insufficient leaflet tissue and decreased mobility due to tethering) may necessitate technical modifications. A retrospective review was performed of 31 patients (seven males and 24 females, median age at operation 31 years) with Ebstein's anomaly, who underwent tricuspid valve repair between March 2002 and December 2014. The original Hetzer technique (annulus to annulus approximation) was employed for six patients with a well-formed anterior leaflet. In 25 patients, the tricuspid valve mechanism was restored at the displaced septal leaflet by approximating the anterior leaflet attachment in the true annulus to the displaced septal leaflet attachment in the mid-septum. A bidirectional superior cavopulmonary anastomosis was added in 27 of 31 (87%) patients. No early or late death occurred during the median follow-up of 66 months (1-138 months). Immediate postoperative tricuspid regurgitation was trivial to mild in 22 patients, and the median preoperative, immediate postoperative, and last follow-up tricuspid regurgitation jet areas in 21 adult patients were 23.3 cm2, 10.4 cm2, and 7.0 cm2, respectively. Two patients underwent reoperation at 81 and 119 months postoperatively. Five-year freedom from severe tricuspid regurgitation or reoperation was 93.2%. Restoration of the tricuspid valve mechanism at the level of displaced septal leaflet leads to excellent long-term outcomes. The addition of the bidirectional superior cavopulmonary anastomosis has contributed to the success of this technique.

Left Ventricular End-Systolic Eccentricity Index for Assessment of Pulmonary Hypertension in Infants.

Pulmonary hypertension (PH) is a common problem in the neonatal intensive care unit and is associated with significant morbidity and mortality. The aim of this study was to identify a quantitative echocardiographic marker of septal curvature that can be used to accurately identify PH in NICU infants with concern for PH. Echocardiograms of infants who were prematurely born and infants with persistent pulmonary hypertension of the newborn were performed using a defined protocol for evaluation of PH. Qualitative assessment by a single pediatric cardiologist was used as a reference standard. Qualitative and quantitative parameters of right ventricular (RV) size, pressure, and function were documented. Left ventricular end-systolic eccentricity index (EI) was defined as the ratio of the anterior-inferior and septal-posterolateral cavity dimensions at the mid-ventricular level. A total of 216 infants at risk for PH were included in this study. One hundred forty-three (66%) had an interpretable tricuspid regurgitation jet velocity. While systolic septal flattening was recognized at EIs ≥ 1.15, more than half-systemic RV pressure became apparent at EIs ≥ 1.3. Unlike qualitative assessment of septal flattening, there was high inter-observer agreement for EIs. Quantitative parameters of RV systolic function were impaired only at EIs ≥ 1.3. We suggest that EIs should be incorporated into routine protocols when there is a concern for PH in neonates. This may lead to a more reliable assessment of PH and may reduce inter-observer variability. Correlation of EIs with invasive hemodynamic data is needed to validate our results.

Pulmonary Hypertension Registry of Kerala (PROKERALA) – Rationale, design and methods

BackgroundPulmonary hypertension (PH) is a disease associated with a high morbidity and mortality. There is paucity of data regarding PH from the developing countries including India.Idiopathic pulmonary arterial hypertension is the most important etiological factor in the western world, but PH secondary to rheumatic heart disease, chronic obstructive pulmonary disease and untreated congenital heart disease could well be the predominant causes in developing countries like India.The main objective of the PROKERALA study – Pulmonary hypertension Registry Of Kerala is to collect data regarding the etiology, practice patterns and one-year outcomes of patients diagnosed to have PH. MethodsThe study is a hospital-based registry in the state of Kerala supported and funded by the Cardiological Society of India, Kerala Chapter. A total of 77 hospitals have agreed to participate in the registry. PH was defined as systolic pulmonary artery pressure derived by echocardiography of more than 50mmHg (by tricuspid regurgitation jet) or mean PA pressure more than 25mmHg obtained at cardiac catheterization.A detailed questionnaire is administered which includes the demographic characteristics, risk factors, family history, ECG data, 6 minute walk test distance, chest X ray findings and echocardiographic data. Details of PH specific therapy and one-year follow-up data are collected.From a preliminary survey in the region, we estimated that we will be able to collect 2000 cases over a period of one year.

Pulmonary Hypertension in Heart Failure Patients Presenting at OAUTHC, Ile-Ife, Nigeria.

BACKGROUNDPulmonary hypertension (PH) is common in heart failure patients. Literature on PH in heart failure is sparse in Nigeria. This study was carried out to determine the prevalence of PH in heart failure patients and ascertain the relationship between left ventricular systolic and diastolic function and the degree of PH.METHODSA total of 125 heart failure patients had echocardiography done. PH was diagnosed using tricuspid regurgitation jet and pulmonary ejection jet profile.RESULTSPH was present in 70.4% of heart failure patients. Estimated mean pulmonary arterial pressure increased with increasing severity of systolic and diastolic dysfunction and had significantly negative correlation with ejection fraction, fractional shortening, and early mitral annular tissue diastolic velocity (E′), but positive correlation with left ventricular end-systolic volume, right ventricular dimension, transmitral E to A ratio, and E/E′ ratio.CONCLUSIONPH is very common in heart failure and has significant relationship with left ventricular function.

Gross right heart dilatation secondary to Ebstein's anomaly.

Cardiac imaging is essential for the diagnosis and follow-up individuals with congenital heart disease (CHD). Currently echocardiography is the first-line investigation, although no single imaging technique is sufficient for complete evaluation of cardiac anatomy and physiology in these patients. Increasingly, adults with CHD are referred for cardiac magnetic resonance (CMR) imaging. The high spatial resolution, functional assessment capabilities and excellent reproducibility of CMR make it a desirable investigation for CHD [1]. Ebstein's anomaly is a rare (incidence ≈1 in 200 000 live births) congenital heart disorder characterized by malformations of the tricuspid valve (TV) and right ventricle (RV). The hallmark features are clearly demonstrated in this CMR study. They are: Malposition of the posterior and septal TV leaflets in the walls of the RV with enlargement, fenestration and/or tethering of the anterior leaflet. Dilatation of the true atrio-ventricular junction and downward displacement of the functional TV annulus. Atrialization of the RV [2]. In the four-chamber view (Fig. 1A), the grossly dilated right heart is clearly evident, with an atrialized RV and dilated tricuspid annulus. The enlarged anterior TV leaflet is well visualized (red arrow), as is the hypoplastic septal leaflet (yellow arrow). The LA and LV are small, owing to compression from the volume-overloaded right heart. Figure 1: (A) CMR four-chamber cine view. Seen here is the grossly dilated right heart, with an atrialized RV and dilated tricuspid annulus. The enlarged anterior TV leaflet is well visualized (red arrow), as is the mislaid and hypoplastic septal leaflet (yellow ... The massively dilated atrial and ventricular portions of right heart are visualized in the short-axis cine view (Fig. 1B). Again the tricuspid valve septal leaflet is seen (red arrow) and the pale jet of tricuspid regurgitation is notable during systole. The intraventricular septum flattened during diastole consistent with right-sided volume overload and there is slow filling of the LV consistent with ventricular–ventricular interaction.

Prevalence of pulmonary hypertension in children with sickle cell disease

Background: To determine the prevalence of elevated pulmonary artery pressures and associated risk factors in children with sickle cell disease. Methods: A descriptive and cross sectional observational study was done over the period of 12 months (March-2013 to Feb-2014). All patients between the age group of 5 to 18 years diagnosed to have Sickle Cell Syndromes were included. A complete physical examination was performed and the details of patient’s age, age at diagnosis, age at first transfusion, frequency of transfusion, history of sickling crisis including the type and number of crisis were analyzed. Investigations done were complete hemogram with reticulocyte count, liver function tests, renal function tests, chest radiograph, electrocardiogram and a 2D echocardiogram. Quantitative data was analyzed by proportion and Chi square test. Results: Total 50 patients (30 males, 20 females) were enrolled in the study between the age group of 5-18 years with the mean age 11.3 ± 3.7 years. Overall prevalence of pulmonary hypertension (PHT) was 38%. Mild PHT (TR Jet velocity 2.5 to 2.9m/second) was found in 12 (24%) patients, 7 (14%) patients had moderate to severe PHT (TR jet velocity >3 m/second).Elevated tricuspid regurgitant jet velocity was more in patients with Hb-SS disease (38.6%) as compared Hb-S/β+ thalassemia (36.6%). A high reticulocyte count (p=0.036), low hemoglobin (p=0.046), increased number of crisis (p=0.048), more frequent packed red cell transfusions (p=0.043), high LDH (p=0.045) and a high bilirubin levels (p=0.041) were significantly associated with elevated pulmonary artery pressures. There was no difference in age of presentation, gender, age of first packed red cell transfusion between patients with and without elevated PHT. Conclusions: High pulmonary artery pressures do occur in children with sickle cell disease. Screening by echocardiography can lead to early detection and intervention.

Percutaneous CT guided lung biopsy in patients with pulmonary hypertension: Assessment of complications

PurposeTo assess the complications of CT-guided percutaneous transthoracic needle aspiration and/or core biopsy (PTNAB) of lung nodules in patients with pulmonary arterial hypertension (PHTN). Method and materialsWe analyzed PTNAB of 74 lung lesions (mean size: 3.6±2.1 cm) in 74 patients (M: F 38:36; age 68±15 years) with documented PHTN on cardiac ultrasound. 39 patients with lung lesions (M: F 24:15; age 65±14) who underwent PTNAB in the same period with right ventricle systolic pressure (RVSP) <35mmHg were selected as controls. Pulmonary arterial pressures were estimated on cardiac ultrasounds by using the tricuspid regurgitation jet method. Two thoracic radiologists reviewed the medical records and PTNAB images on a PACS station and documented nodule size, location, distance traversed in lung, technical success and complications. ResultsFine needle aspirates were obtained in all and core biopsy in 23% (17/74) of the nodules. 61% (45/74) of the nodules were in the middle and 39% (29/74) were in the outer third of lung. PHTN was mild, moderate and severe in 84% (62/74), 13% (10/74) and 3% (2/74) of the patients. Biopsy was complicated by hemorrhage in 26% (19/74), moderate hemoptysis in 1.3% (1/74), pneumothorax in 17% (12/74), chest tube in 1.3% (1/74) and hemothorax in 1.3% (1/74) of the patients. The complications rate in control group was similar, hemorrhage in 33% (19/39) (p=0.6), moderate hemoptysis in 5% (2/39) (p=0.3), pneumothorax in 28% (11/39) (p=0.2), chest tube in (0/39) (p=0.3), and hemothorax in 3% (1/39) of the patients (p=0.7). ConclusionPercutaneous needle biopsy of lung lesions in patients with mild to moderate PHTN can be performed without significant increase in complications.

Kidney Disease among Patients with Sickle Cell Disease, Hemoglobin SS and SC

Sickle cell disease (SCD) is an inherited anemia that afflicts millions worldwide. Kidney disease is a major contributor to its morbidity and mortality. We examined contemporary and historical SCD populations to understand how renal disease behaved in hemoglobin SS (HbSS) compared with HbSC. Kidney function was examined in the multicentered Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) Trial (HbSS=463; HbSC=127; years 2007-2009) and historical comparator populations from the Cooperative Study of Sickle Cell Disease (CSSCD; HbSS=708) and the Multicenter Study of Hydroxyurea in Sickle Cell Disease (MSH; HbSS=299). In adults with SCD, eGFR was lower among older individuals: -1.78 ml/min per 1.73 m(2) per year of age (95% confidence interval [95% CI], -2.06 to -1.50; Walk-PHaSST Trial), -1.75 ml/min per 1.73 m(2) per year of age (95% CI, -2.05 to -1.44; MSH), and -1.69 ml/min per 1.73 m(2) per year of age (95% CI, -2.00 to -1.38; CSSCD) in HbSS compared with -1.09 ml/min per 1.73 m(2) per year of age (95% CI, -1.39 to -0.75) in HbSC (Walk-PHaSST Trial). Macroalbuminuria was seen in 20% of participants with SCD (HbSS or HbSC; P=0.45; Walk-PHaSST Trial), but microalbuminuria was more prevalent in HbSS (44% versus 23% in HbSC; P<0.002). In the Walk-PHaSST Trial, albuminuria was associated with hemolysis (higher lactate dehydrogenase, P<0.001; higher absolute reticulocyte count, P<0.02; and lower Hb, P=0.07) and elevated systolic BP (P<0.001) in HbSS. One half of all participants with HbSS (20 of 39) versus one fifth without (41 of 228) elevated tricuspid regurgitant jet velocity (≥3 m/s; adverse prognostic indicator in SCD) had macroalbuminuria (P<0.001). In the CSSCD, overt proteinuria, detected (less sensitively) by urine dipstick, associated with higher 3-year mortality (odds ratio, 2.48; 95% CI, 1.07 to 5.77). Serum bicarbonate was lower in HbSS (23.8 versus 24.8 mEq/dl in HbSC; P<0.05) and associated with reticulocytopenic anemia and decreased renal function. In SCD, albuminuria or proteinuria was highly prevalent, in HbSS more than in HbSC. Proteinuria associated with mortality in HbSS. Older individuals had a lower than expected eGFR, and this was more prominent in HbSS. Current management does not routinely address renal complications in SCD, which could plausibly reduce morbidity and mortality.

Albuminuria Is Associated with Endothelial Dysfunction in Sickle Cell Disease

Introduction: Albuminuria is a common and sensitive marker of glomerular injury in SCD. We and others have previously observed the association of albuminuria with echocardiographically-derived tricuspid regurgitant jet velocity, systolic blood pressure, and history of stroke, suggesting a shared vasculopathic pathophysiology. However, the pathogenesis of albuminuria in SCD remains poorly defined. The purpose of this study was to evaluate the association of albuminuria with endothelial dysfunction, assessed non-invasively using ultrasound imaging of the brachial artery in SCD patients. In addition, we evaluated the association of albuminuria assessed by spot urine collection with 24-hour urine collections for protein.Methods: Spot urine measurements for microalbumin/creatinine ratio (UACR) were obtained during the "non-crisis," steady state over 2-3 visits, with a 24-hour urine collection for assessment of protein at the final visit. We obtained routine laboratory tests, including markers of hemolysis (lactate dehydrogenase, and total and indirect bilirubin) at the baseline visit. Endothelial function was assessed non-invasively at the final visit using a brachial artery shear stress method, with measurements of flow-mediated dilation (FMD), an index of endothelium-dependent vasodilation and nitroglycerin-mediated dilation (NTMD), a measure of endothelium-independent vasodilation. Patients on renin-angiotensin-aldosterone system (RAAS) blocking agents (ACE-inhibitors, angiotensin receptor blockers, direct renin inhibitors and mineralocorticoid receptor blockers), as well as those on hydroxyurea were on a stable dose for at least 3 months prior to enrollment. We evaluated associations between measures of endothelial function and other study covariates using Spearman's correlation coefficient for continuous covariates, and the Kruskal Wallis test for categorical covariates. Linear regression analysis was used to adjust for baseline arterial diameter. Reported p-values are for individual tests, unadjusted for multiple comparisons.Results: Spot urine samples were obtained in 23 subjects with sickle cell anemia (female = 13, male = 10), mean age, 43.3 ± 12.0 years, with normoalbuminuria (UACR < 30 mg/g creatinine) in 7 subjects, microalbuminuria (UACR = 30 - 299mg/g creatinine) in 9 subjects and macroalbuminuria (UACR ³300 mg/g creatinine) in 7 subjects. Albuminuria (assessed by spot microalbumin/creatinine ratio) was significantly correlated with FMD (ρ = -0.45, p = 0.031). However, albuminuria was no longer significantly associated with FMD when controlled for baseline arterial diameter (p = 0.09). Although FMD appeared to be lowest in patients with macroalbuminuria, no significant difference was observed when FMD was evaluated in the 3 albuminuria categories (p = 0.16). No significant correlations were observed between NTMD and albuminuria (ρ = 0.35, p = 0.20). Surprisingly, no significant correlations were observed between FMD and hemoglobin, fetal hemoglobin, lactate dehydrogenase or indirect bilirubin. We observed a strong correlation between albuminuria assessed by spot microalbumin-creatinine ratio and total urinary protein assessed by 24-hour urine collection (ρ = 0.90, p < 0.0001). Furthermore, albuminuria assessed by spot microalbumin-creatinine ratio was strongly correlated with urine aliquots for microalbumin-creatinine ratio obtained from the 24-hour urine collection (ρ = 0.97, p < 0.0001).Conclusion: In this exploratory study, we found that albuminuria is significantly correlated with FMD in patients with SCD, suggesting that endothelial dysfunction may contribute to the pathogenesis of this complication in SCD. We also find a very strong correlation between spot urine assessments for microalbumin/creatinine ratio and 24-hour urine collections for protein, providing validation for the use of spot urine assessments for the evaluation of albuminuria in patients with SCD. DisclosuresArcher:Global Blood Therapeutics: Consultancy.

The Effects of Glutamine Supplementation on Markers of Autophagy and Apoptosis in Peripheral Blood Mononuclear Cells from Patients with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is a hemoglobinopathy associated with an increased risk of pulmonary hypertension (PH) due to a number of mechanisms that includes iron overload, hemolysis, erythrocyte-derived arginase (which limits both nitric oxide and arginine bioavailability), functional splenectomy, and a hypercoagulable state among others. Glutathione (GSH, and its oxidized pair glutathione disulfide GSSG) is the principal thiol redox buffer in erythrocytes, which has been linked to hemolysis when depleted. Glutamine is not only a precursor to GSH, but also plays an anti-oxidant role through preservation of the intracellular nicotinamide adenine dinucleotide (NAD) levels, required for reducing GSSG back to GSH, thus decreasing the risk for hemolysis. Low erythrocyte glutamine levels are associated with risk of PH as defined by a tricuspid regurgitant jet velocity of (TRV) ≥2.5 m/s measured by Doppler echocardiography. SCD also exhibits an elevated level of circulating leukocytes, known as leukocytosis, which may contribute to vascular occlusion. The mechanism by which leukocytosis occurs is currently unknown. However, leukocyte cell death can be informative on the regulation of leukocyte cell numbers and measurement of mitochondrial BAX and caspase 9, are classic indicators of an active intrinsic cell death pathway. Autophagy is responsible for the turnover of macromolecules and organelles via the lysosomal degradative pathway. In this pathway, LC3 is important for the maturation and transport of autophagosomes and therefore, a reflection of autophagic activity. Autophagy ensures cell survival under certain conditions of nutrient deprivation or growth factor withdrawal and has also been implicated in innate and adaptive immune responses. In this study, the mitochondrial apoptotic marker BAX and the autophagy marker LC3 were examined in a SCD trial of glutamine therapy in patients at risk for PH.Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples taken from SCD (n=13) and control patients (n=7) and BAX and LC3 were measured via western blot analysis. Western blot results were evaluated via densitometry. SCD patients with PH-risk were treated with oral L-glutamine supplementation (10 mg TID) with the objective of estimating the level of cell death and autophagy proteins in circulating PBMCs from SCD patients at baseline and after glutamine supplementation. SCD patients were sampled at baseline (BL),and then at two weeks (W2), four weeks (W4), six weeks (W6), and eight weeks (W8) during the glutamine therapy.Results: Mean age for patients with SCD was 46±14; 39% were male with 54% having Hb-SS, while 46% had Hb-SC. Mean TRV was 3.0±0.6 m/s. The mean age for controls was 32± 12 and 57% were male; all controls were Hb-AA with a mean TRV of 1.8±0.6. At baseline there was no statistical difference in BAX expression between control and SCD patients. In comparison to baseline, however, supplementation with glutamine in SCD patients resulted in significantly increased expression of BAX in PMBCs by 15% over the 8 weeks of therapy; potentially indicating a restorative effect of glutamine on the intrinsic mitochondrial apoptotic pathway, which may ultimately reduce leukocytosis. In contrast, glutamine supplementation over 8 weeks, significantly reduced LC3 expression by 42% in PBMCs, suggesting a decrease in cellular autophagy, thus reducing the ability for PBMCs to remain in circulation.Conclusions: At baseline there was no difference in BAX expression between control and SCD patients, however, after 8 weeks of glutamine supplementation, PBMCs had an increased BAX expression and a decreased LC3 expression. This suggests that PBMCs from glutamine supplemented SCD patients may lose their ability to remain in circulation via apoptosis upregulation and autophagy downregulation DisclosuresWalter:Novartis: Research Funding.

A randomized pilot study on the effect of niacin on pulmonary arterial pressure.

BackgroundNiacin induces the release of vasodilating prostaglandins, for which receptors are present within the pulmonary arterial circulation. We hypothesized that immediate-release niacin would reduce right ventricular systolic pressure in patients with pulmonary hypertension in a randomized, double-blinded, single-dose provocation study.MethodsWe recruited inpatient subjects with a Doppler echocardiogram showing a peak tricuspid regurgitation (TR) jet velocity of 2.7 m/s or greater, and who were free of known pulmonary vascular disease. Subjects were randomized in a 1:2:2 ratio to receive a single dose of either placebo, niacin 100 mg or niacin 500 mg, respectively. TR jet velocities were measured immediately before, and 1 hour post dose, corresponding to peak niacin absorption and prostaglandin release. The primary endpoint was the change in mean TR jet velocity measured over ten successive cardiac cycles.ResultsThe baseline mean estimated right ventricular systolic pressure (RVSP) for all 49 subjects (25 male) was 51.9 ± 12.1 mm Hg. The primary endpoint of mean change in TR jet velocity was 0.016 ± 0.065 m/s in the placebo group, compared to −0.017 ± 0.065 m/s with niacin 100 mg, and −0.063 ± 0.038 m/s with niacin 500 mg (P = 0.63). The change in maximum estimated RVSP across the three drug groups was 0.2 ± 1.6 mm Hg, −1.3 ± 1.8 mm Hg and −2.2 ± 1.2 mm Hg (P = 0.62). In exploratory pairwise analysis in the high-dose niacin group (500 mg), the reduction in mean RVSP was from 50.9 ± 9.4 mm Hg to 48.7 ± 10.0 mm Hg (P = 0.09).ConclusionsA single dose of immediate-release niacin (100 mg or 500 mg) had no significant effect on RVSP 1 hour post administration. A nonsignificant dose-dependent trend for a modest reduction in RVSP, most notable in the 500 mg group, was noted.(ISRCTN number 12353191, registered April 23, 2015).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1013-6) contains supplementary material, which is available to authorized users.

Serum apelin as a novel non-invasive marker for subclinical cardiopulmonary complications in children and adolescents with sickle cell disease

BackgroundCardiovascular involvement represents a leading cause of mortality and morbidity in sickle cell disease (SCD). Apelin is a peptide involved in the regulation of cardiovascular function. AimTo determine serum apelin among 40 children and adolescents with SCD compared with 40 healthy controls and assess its relation to markers of hemolysis, iron overload as well as cardiopulmonary complications. MethodsSCD patients, in steady state and asymptomatic for heart disease, were studied stressing on hydroxyurea/chelation therapy, hematological profile, serum ferritin and apelin levels. Full echocardiographic study including assessment of biventricular systolic function and pulmonary artery pressure was done. ResultsApelin levels were significantly lower in SCD patients compared with controls (P<0.001). Cardiopulmonary complications were encountered in 30% of patients. Apelin was significantly decreased among patients with cardiopulmonary disease (P=0.006) whether those at risk of pulmonary hypertension (P=0.018) or patients with heart disease (P=0.043). Hydroxyurea-treated patients had higher apelin levels than untreated ones (P=0.001). Apelin was negatively correlated to lactate dehydrogenase, indirect bilirubin, serum ferritin, end systolic diameter, tricuspid regurgitant jet velocity, right ventricle systolic pressure, pulmonary vascular resistance and tissue Doppler imaging S wave. Apelin cutoff value of 1650ng/L could significantly detect the presence of cardiopulmonary complications in SCD with 90.9% sensitivity and 72.4% specificity. ConclusionApelin is a promising marker for screening of SCD patients at risk of cardiopulmonary disease because it is altered during the early subclinical stage of cardiac affection. A combination of apelin and echocardiography provides a reliable method to assess cardiopulmonary affection in young SCD patients.

Intracardiac Doppler Echocardiography for Monitoring of Pulmonary Artery Pressures in High-Risk Patients Undergoing Transcatheter Aortic Valve Replacement

Uncontrolled pulmonary hypertension may cause worse outcomes after transcatheter aortic valve replacement (TAVR), while hemodynamic monitoring is desirable for risk control. Pulmonary artery pressure (PAP) readings obtained by intracardiac Doppler echocardiography were evaluated. In 114 patients with symptomatic aortic stenosis and median Society of Thoracic Surgeons scores of 10.5% (interquartile range, 7.7%-15.0%), transfemoral and transapical TAVR was guided by intracardiac Doppler echocardiography. The continuous-wave Doppler beam interrogated the jet of tricuspid regurgitation from the "home view" position. Systolic PAP (PAPs) was estimated as the sum of the pressure gradient derived from the maximum transtricuspid regurgitation jet velocity and the central venous pressure. Mean PAP (PAPm) was calculated by the mean gradient method (1) and the Chemla formula (2). Measurements were obtained immediately before and after TAVR. Pre- and postinterventional readings showed marginal pressure underestimation in comparison with measurements derived from right-heart catheterization: PAPs, -2.7 (95% CI, -3.3 to 2.1) and -1.4 (95% CI, -1.9 to -0.9); PAPm by the mean gradient method, -1.9 (95% CI, -2.2 to -1.6) and -0.1 (95% CI, -0.4 to 0.2). Agreement (95% limits) for PAPs was -8.6 to 3.2 and -6.8 to 4.0; agreement for PAPm by the mean gradient method was -5.4 to 1.6 and -3.4 to 3.2. The repeatability coefficient (95% limits of agreement) for PAPs was excellent: 3.4 (-4.2 to 2.5) and 5.5 (-5.3 to 5.8); repeatability for PAPm was higher by the mean gradient method than by the Chemla method. In ≥ 85% of patients with pulmonary hypertension, PAPm improved after valve deployment. Intracardiac Doppler echocardiography-derived monitoring of PAP by the mean gradient method is accurate and well applicable to high-risk TAVR candidates for intraprocedural risk control.

Risk Factors of Pulmonary Hypertension in Brazilian Patients with Sickle Cell Anemia.

This study was a prospective cross-sectional cohort study of 125 patients with sickle cell anemia (SS) between the ages of 16 to 60 years. Enrolled patients were followed-up prospectively for 15 months. Demographic, clinical, hematological and routine biochemical data were obtained on all patients. Six-minute walk test and Doppler Echocardiography were performed on all patients. A tricuspid regurgitant jet velocity (TRJV) < 2.5 m/sec was considered normal, 2.5 ≤ TRJV ≤ 3.0 was considered mild-moderate and > 3.0 m/sec, severe. Patients with abnormal TRJV were significantly older and more anemic, had significantly higher lactate dehydrogenase (LDH) levels, reticulocyte count and incidence of death. The logistic multimodal model implemented for the 125 patients indicated that age was the covariate that influenced the outcome of normal or abnormal TRJV with a cutoff age of thirty-two years. The survival rate for the group of patients with creatinine (Cr) > 1.0 mg/dL was lower than the group with Cr ≤ 1 and normal TRJV. A coefficient matrix showed that the LDH values were weakly correlated with the reticulocyte count but strongly correlated with hemoglobin suggesting that the TRJV values were not correlated with the hemolytic rate but with anemia. Ten patients died during the follow-up of whom 7 had TRJV > 2.5 m/sec. Acute chest syndrome was the most common cause of death followed by sepsis. In conclusion, this study shows that patients with SS older than thirty-two years with high LDH, elevated TRJV, severe anemia and Cr > 1 have poor prognosis and may be at risk of having pulmonary hypertension and should undergo RHC.

Aging in Sickle Cell Disease: Co-morbidities and New Issues in Management

Availability of hydroxyurea (HU) coupled with early therapeutic interventions has increased the life expectancy of patients with sickle cell disease. Hence, the sickle cell community needs to be aware of common diseases of aging that survivors are predisposed to. We chose to investigate the sickle cell disease-related complications as well as non sickle cell disease-related medical problems of aging in 45 sickle cell patients over the age of 40 years. The most frequent chronic complications of sickle cell disease were elevated tricuspid regurgitant jet velocity on echocardiogram, chronic renal disease, iron overload and leg ulcers. Medical co-morbidities in this patient group included hypertension, diabetes mellitus (DM), hypercholesterolemia and symptomatic coronary artery disease (CAD). In our cohort, only 38.0% had a primary care doctor. Only 11.0% over age 50 had a screening colonoscopy, and of the women, 42.0% had a screening mammography. Medical co-morbidities and lack of health maintenance in older sickle cell patients are likely to impact overall health and mortality. Aging patients with sickle cell disease may benefit from a primary medical home for age appropriate comprehensive health care.

Correlation between Pulmonary Artery Pressure Measured by Echocardiography and Right Heart Catheterization in Patients with Rheumatic Mitral Valve Stenosis (A Prospective Study)

Right heart catheterization (RHC) remains the gold standard for hemodynamic assessment of the right heart and pulmonary artery. However, this is an invasive tool, and noninvasive alternatives such as transthoracic echocardiography (TTE) are preferable. Nonetheless, the correlation between measurements by TTE and RHC are debated. In this study, we prospectively examined the correlation between systolic and mean pulmonary artery pressures (sPAP and mPAP) measured by RHC and TTE in patients with hemodynamically significant rheumatic mitral stenosis (MS). Three hundred patients with hemodynamically significant MS undergoing TTE who were scheduled to undergo RHC within 24 hours were analyzed. PAP measurements were taken for all patients by RHC (sPAP(RHC), mPAP(RHC)). Maximum velocity of tricuspid regurgitation (TR) jet obtained by continuous-wave Doppler with adding right atrial (RA) pressure was used for measuring sPAP by TTE (sPAP(TRVmax)). Mean PAP was measured using either pulmonary artery acceleration time (mPAP(PAAT)) method or by adding RA pressure to velocity-time integral of TR jet (mPAP(TRVTI)). A good correlation between sPAP(RHC) and sPAP(TRVmax) (r = 0.89, P < 0.001), between mPAP(RHC) and mPAP(PAAT) (r = 0.9, P < 0.001), and between mPAP(RHC) and mPAP(TRVTI) (r = 0.92, P < 0.001) was found. Sensitivity and specificity of sPAP(TRV) max in detecting pulmonary hypertension (PH) were 92.8% and 86.6% and of mPAP(PAAT) were 94.1% and 73.3%, respectively. The noninvasive assessment of sPAP and mPAP by TTE correlates well with invasive measurements and has an acceptable specificity and sensitivity in detecting PH in patients with hemodynamically significant MS.