Tricuspid Regurgitant Jet Research Articles

Device closure of atrial septal defect with severe pulmonary hypertension in adults: Patient selection with early and intermediate term results.

To describe a subset of atrial septal defect (ASD) with severe pulmonary hypertension (PHT) that is suitable for closure. As per American Heart Association/American College of Cardiology guidelines, ASD with elevated pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) >2/3rd systemic is considered as a contraindication for closure. Patients with anatomically large ASD measuring >25 mm and a high probability of reversible pulmonary vascular disease were subjected to fenestrated device closure, despite severe PHT and elevated PVR. They were discharged on pulmonary vasodilators and were followed for 39.5 ± 8.5 months. Four patients had repeat cardiac catheterization. Six patients underwent successful device closure of large ASD with severe PHT. Their basal Qp:Qs was 2.8 ± 0.3:1 while the systolic PAP and the PVR index (PVRI) were 102.6 ± 11.5 mm Hg and 9.6 ± 1.6 Wu m2 , respectively. Post 100% oxygen inhalation, the Qp:Qs increased to 3.5 ± 0.3:1, systolic PAP remained 103.5 ± 7.6 mm Hg while the PVRI dropped to 5.4 ± 1.1 Wu m2 . The postballoon occlusion systolic PAP decreased to 86.6 ± 8.8 mm Hg. At the last follow-up, their pulmonary artery systolic pressure by tricuspid regurgitation (TR) jet decreased from 105.6 ± 12.6 mm Hg to 45 ± 7.0 mm Hg. During follow-up cardiac catheterization (n = 4), the systolic PAP and PVRI were 55.7 ± 9.2 mm Hg and 3.2 ± 0.4, respectively. Patients with anatomically big defect and a large left to right shunt at baseline with a high probability of reversible PVR benefit with ASD closure and pulmonary vasodilators, despite significantly elevated PAP and PVRI.

Use of prostaglandin E1 to treat pulmonary hypertension in congenital diaphragmatic hernia

Background/PurposeProstaglandin E1 (PGE) has been used to maintain ductus arteriosus patency and unload the suprasystemic right ventricle (RV) in neonates with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension (PH). Here we evaluate the PH response in neonates with CDH and severe PH treated with PGE. MethodsWe performed a retrospective chart review of CDH infants treated at our center between 2011 and 2016. In a subset, PGE was initiated for echocardiographic evidence of severe PH, metabolic acidosis, or hypoxemia. To assess PH response, we evaluated laboratory data, including B-type natriuretic peptide (BNP) and echocardiograms before and after PGE treatment. Categorical and continuous data were analyzed with Fisher's exact tests and Mann–Whitney t-tests, respectively. ResultsFifty-seven infants were treated with PGE a mean 17 ± 2 days. BNP levels declined after 1.4 ± 0.2 days of treatment and again after 5.2 ± 0.6 days. After 6 ± 0.8 days of treatment, echocardiographic estimates of severe PH by tricuspid regurgitation jet velocity, ductus arteriosus direction, and ventricular septum position also improved significantly. Treatment was not associated with postductal hypoxemia or systemic hypoperfusion. ConclusionsIn patients with CDH and severe PH, PGE is well tolerated and associated with improved BNP and echocardiographic indices of PH, suggesting successful unloading of the RV. Type of studyTreatment study. Level of evidenceLevel III.

Aortic Stenosis with Severe Tricuspid Regurgitation: Comparative Study between Conservative Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement Combined With Tricuspid Repair

Severe aortic stenosis (AS) and severe tricuspid regurgitation (TR) may coexist. The aim of this study was to determine the change in right ventricular (RV) function and TR after surgical aortic valve replacement combined with tricuspid valve repair (SAVR+TVr), transcatheter aortic valve replacement (TAVR), or conservative management and compare outcomes dependent on RV functional parameters and treatment allocation. A retrospective analysis was conducted in 147 consecutive patients with severe AS and TR of baseline and 6-month clinical and echocardiographic parameters, including quantitative estimation of RV size and function (end-diastolic and end-systolic areas, tricuspid annular plane systolic excursion, fractional area change, and Tei index). SAVR+TVr and TAVR were associated with superior reduction in TR jet area after 6months (P=.01 for time×group interaction) compared with conservative therapy. However, RV function (tricuspid annular plane systolic excursion and stroke volume) improved after TAVR but not after SAVR+TVr (P=.007 and P=.02 for time×group interaction, respectively). Conservative therapy for combined AS and TR was associated with >80% mortality in <4years. TAVR and SAVR+TVr were associated with improved survival compared with conservative therapy (P<.0001), without significant difference between each other. Quantitative RV functional parameters were associated with poor outcomes, including tricuspid annular plane systolic excursion (P=.002), Tei index (P=.02), and RV fractional area change (P=.03). In this nonrandomized, retrospective, observational study, SAVR+TVr and TAVR were associated with reductions in TR in patients with severe AS combined with severe TR. Importantly, RV function improved after TAVR but not after SAVR+TVr. Patients with severe AS and TR have a very poor prognosis with conservative therapy. When contemplating invasive procedures, assessment should include quantitative functional RV parameters.

Sleep Apnea is not Associated with Elevations in Pulmonary Artery Pressure in a Clinical Cohort

Introduction Pulmonary hypertension (PH) is associated with adverse patient outcomes. Apneic events during sleep cause transient elevations in pulmonary artery pressure, however the association between sleep apnea and persistent daytime PH is less clear. Hypothesis We hypothesized that sleep apnea would be associated with elevated pulmonary artery systolic pressure (PASP) through both direct effects of hypoxia and indirect effects on left ventricular function. Methods We examined the electronic medical records of patients age ≥ 18 years undergoing sleep study within our large multisite hospital system between March 1999 and December 2015 who had an echocardiogram within 12 months of sleep study. Patients with severe left-sided valve disease (n=33), missing PASP (n=736), or missing apnea hypopnea index (AHI) (n=9) were excluded. An AHI ≥15 events/hour was used to define sleep apnea. PASP was noninvasively estimated by Doppler interrogation of the tricuspid regurgitant jet. Multivariable linear regression was used to examine associations between AHI and measures of left ventricular function and PASP. Results A total of 5,075 patients (age 58.2 ± 14.4 years; 53.0% female) were included. Sleep apnea was found in 45.4% of patients. Mean PASP was 33 ± 15 mm Hg with 34.8% having PASP ≥ 36 mmHg. Patients with higher AHI were older, more likely to be male, and had higher body mass index (BMI). Compared to patients without sleep apnea, those with sleep apnea had lower ejection fraction (EF) (53.6 vs 55.4%), higher left ventricular mass index (LVMI) (105 vs 92 g/m 2 ), and higher early mitral inflow to early diastolic mitral annual velocity ratio (E/e’) (11.9 vs 10.8). After adjustment for age, sex, site, and BMI, EF was 0.9 percentage points lower (95% CI [0.4, 1.4]), LVMI was 7.0 g/m 2 higher [5.1, 8.9], and E/e’ was 0.6 higher [0.1, 1.0] in patients with sleep apnea. In contrast, patients with and without sleep apnea had similar PASP (33.9 vs 33.2 mmHg; p=0.08). These findings persisted when limiting analysis to the 1,784 patients who underwent sleep study prior to echocardiogram. Conclusions In this analysis of real world patients referred for sleep study and echocardiogram, although sleep apnea was associated with markers of left ventricular dysfunction, we found no association between sleep apnea and PASP. This finding suggests sleep apnea does not directly elevate daytime pulmonary artery pressure. Elevations in PASP from left ventricular dysfunction may take time to develop and may not be apparent on cross-sectional analysis. Longitudinal follow-up of pulmonary artery pressure trajectories in patients with sleep apnea will provide greater insights on the impact of sleep apnea on PH.

The association of nocturnal hypoxia and an echocardiographic measure of pulmonary hypertension in children with sickle cell disease.

Pulmonary hypertension (PH) is multifactorial in origin and may develop early in children with sickle cell disease (C-SCD). Potential etiologies are hemolysis-induced endothelial dysfunction, left ventricular (LV) dysfunction, and chronic hypoxia. Nocturnal hypoxia (NH) in C-SCD is known to be a sequela of obstructive sleep apnea (OSA). The primary objective of this study is to correlate polysomnographic evidence NH with echocardiographic measures of PH in C-SCD. We performed a retrospective chart review of 20 C-SCD (Hemoglobin SS), who had polysomnography and echocardiogram performed within a narrow time interval, and 31% of them had pre-existing cardiac conditions. Tricuspid regurgitant jet velocity (TRJV) ≥ 2.5 m/s was considered as an indicator of PH. Twenty-five percent of the subjects had NH. Forty percent of C-SCD, predominantly male, had evidence of PH based on an elevated TRJV. Children with NH compared to non-NH had significantly worse baseline hypoxemia (p < 0.001), higher TRJV (p = 0.005), and higher LV end-diastolic diameters (p = 0.009). The severity of NH was influenced by OSA. However, PH was not associated with OSA or duration of hydroxyurea therapy. Our study indicates that NH is associated with PH in C-SCD, and that screening for NH may help to identify C-SCD with higher morbidity risk.

Successful Living Donor Liver Transplantation in a Case of Mean Pulmonary Arterial Pressure of 52 mmHg

Introduction Pulmonary hypertension (PH) is defined as an elevated mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest. The perioperative management can be complicated by hemodynamic instability resulting in severe hypoxemia, acute right heart failure/circulatory collapse and death. Portal hypertension is a curable cause for PH. However, Krowka et al reported that mPAP of 50 mmHg or greater was associated with 100% cardiopulmonary mortality in liver transplantation (LT) setting. Materials and Methods A 45 years old male patient underwent LDLT for HBV + alcoholic cirrhosis and HCC. MELD score was 28. Echocardiography performed 2 months before the operation showed right ventricular systolic pressure (RVSP) 62 mmHg and maximum tricuspid regurgitant jet velocity (TRVmax) 3.8m/sec, suggesting moderate resting PH. During anesthetic induction, pulmonary vascular resistance (PVR) was measured as 246 dynes/sec/cm-5 and mPAP as 52mmHg. One hour later, they were 217 and 40, respectively, with infusion of Isosorbide 1mcg/Kg/min. Vital signs were stable and PaO2 level was 223 mmHg. So we decided to proceed with surgery despite of moderate PH. Results Graft weighed 550g and GRWR was 0.74. The living donor LT procedure was done with modified right lobe graft. Additionally portal vein endthrombectomy, direct ligation of a large splenorenal shunt and splenic artery ligation was done. The operation took 850 minutes and 24 pints of RBC, 16 pints of FFP, 8 pints of PC and 10 pints of cryoprecipitate. PVR and mPAP were in the range of 217~149 and 46~31, respectively. Alprostadil 7mcg/hr was started just after finishing arterial anastomosis and was infused for 7 days thereafter. Extubation was done 9 hours after the operation and liquid diet was begun 2 days after the operation. The day after LT, RVSP was 96 mmHg and TRVmax 4.9m/sec. And 5 days after LT, he complained of dyspnea and Beraprost (prostacyclin pathway agonist) was given orally. Even with mild dyspnea, the patient was discharged on foot 19 days after LT. 6 weeks after LT RVSP was measured as 84 mmHg and TRVmax 4.0m/sec. mPAP was 63 mmHg on right heart catheterization. On CT scan, there was marked hepatic congestion resulting from pulmonary hypertension. Endothelin receptor antagonist Ambrisentan was given orally. The patient's breathing difficulty almost disappeared soon. Now, 3 months after the operation, he returned to work. Conclusion The authors conducted LDLT in a case of severe pulmonary hypertension with mean PAP 50 mmHg successfully by careful intraoperative monitoring and postoperative management. When encountered a case of moderate to severe pulmonary hypertension during LT, initial response to anesthetic management might dictate whether to proceed with LT or not.

Clinical and Laboratory Predictors of Elevated TRV In Sickle Cell Anaemia

Pulmonary hypertension (PH) has become an increasingly recognized complication in sickle cell anaemia (SCA) and is a major cause of morbidity and mortality. Though the burden of SCA in sub-Saharan Africa is high, there is paucity of data on SCA-associated PH with little or no attention given to it in routine patient care. The current study therefore sought to determine the prevalence of PH and its associated risk factors among adult patients with SCA. This was a cross-sectional study involving 76 clinically stable, hydroxyurea-naive participants. We obtained socio-demographic and clinical history. Measurement of Tricuspid Regurgitant jet Velocity (TRV) was obtained via transthoracic echocardiography and lung function was assessed using spirometry and pulse oximetry. Other investigations were complete blood counts, free plasma haemoglobin, serum urea and creatinine. Twenty-five (32.9%) of study participants had elevated TRV (≥ 2.5m/s) on Doppler echocardiography, which was suggestive of raised pulmonary artery systolic pressure. There were significant associations between elevated TRV and steady-state haemoglobin (p &lt; 0.001), blood urea level (p = 0.030), presence of chronic leg ulcers (p = 0.043) and oxygen saturation (p &lt; 0.001) and these may be identifiable and modifiable risk factors for selective screening with echocardiography in a resource poor setting.

Predictors of Procedural and Clinical Outcomes in Patients With Symptomatic Tricuspid Regurgitation Undergoing Transcatheter Edge-to-Edge Repair

ObjectivesThis study sought to investigate predictors of procedural success and clinical outcomes in patients with tricuspid regurgitation (TR) at increased surgical risk undergoing transcatheter tricuspid valve edge-to-edge repair (TTVR). BackgroundRecent data suggest TTVR using the edge-to-edge repair technique in patients at high surgical risk is feasible and improves functional status at short-term follow-up. MethodsTTVR was carried out in 117 patients with symptomatic TR (median age 79.0 years [interquartile range (IQR): 75.5 to 83.0 years], EuroSCORE II 6.3% [IQR: 4.1% to 10.8%], STS mortality score 5.3% [IQR: 2.9% to 7.1%]) at 2 centers in Germany between March 2016 and November 2017. Seventy-four patients had concomitant severe mitral regurgitation and underwent transcatheter edge-to-edge repair of both valves. ResultsDuring TTVR, 185 and 34 clips were implanted at the anteroseptal and posteroseptal commissures, respectively. Procedural success (TR reduction ≥1) was achieved in 81% of patients. Median TR effective regurgitant orifice area was reduced from 0.5 to 0.2 cm2. After a median follow-up of 184 days (IQR: 106 to 363 days), 24 patients died and 21 patients were readmitted for heart failure. TTVR procedural success independently predicted the time free of death and admission for heart failure (hazard ratio: 0.20 [95% confidence interval: 0.08 to 0.48]; p < 0.01), irrespective of concomitant mitral regurgitation. Small TR coaptation gap size and a central/anteroseptal TR jet location independently predicted procedural success on multivariate analysis. ConclusionsSuccessful TR reduction by TTVR serves as a predictor for reduced mortality and heart failure hospitalization. TR coaptation gap and jet location may assist in decision making whether a patient is anatomically suited for TTVR.

First Description of Tricuspid Valve Dysplasia in a Basset Hound

This report represents the first description of tricuspid valve dysplasia in a Basset hound. We evaluated clinical signs, ECG abnormalities and echocardiographic findings related to tricuspid valve dysplasia in a 6 month Basset Hound. A specific protocol of cardiologic examination was performed every time the patient was evaluated. This protocol included: clinical exam, ECG and echocardiographic investigation. The clinical examination identified over the entire period of surveillance a dog with good body condition score (2.5-3/5), alert, bright, being able to take moderate exercise. A 4/6 left heart base systolic murmur was identified at every examination. ECG revealed a sinus rhythm. Echocardiography identified right heart abnormality, with malposition of tricuspid annulus, one leaflet being short and thick and other extremely long with abnormal motion. Due to abnormal morphology of tricuspid valve apparatus a tricuspid regurgitant jet was noted with Color Doppler. The left heart seemed to have normal morphology. An atrial septal defect was also noticed. Further studies need be performed in order to establish if tricuspid valve dysplasia in Basset hound is a congenital or genetic defect.

VALIDATING THE USE OF PULMONARY ARTERY ACCELERATION TIME IN ESTIMATING PULMONARY PRESSURE IN NEONATES

Abstract BACKGROUND Estimation of right ventricular peak systolic pressure (RVSP) or pulmonary pressure using echocardiography is crucial in neonates with acute or chronic pulmonary hypertension. Conventionally in echocardiography, the maximal velocity of the Tricuspid Regurgitant jet (TR Vmax) is used to estimate the RVSP. However, TR jet can often be absent or unmeasurable in neonates, resulting in a need to search for alternative echocardiographic measures of pulmonary pressure in neonates. Pulmonary Artery Doppler Waveform Parameter known as Pulmonary Artery Acceleration Time (PAAT) has been investigated in adults and older children and found to be reliable in estimating pulmonary pressure. To date, no such validation study exists for neonates.Hence we designed this study to explore the role of Pulmonary Artery Acceleration Time in estimating pulmonary pressures in neonates. OBJECTIVES To identify the pulmonary artery doppler waveform parameter that most closely reflects pulmonary pressure and analyse the impact of baseline variables and measurement techniques on this relationship. DESIGN/METHODS This was a retrospective cohort analysis conducted at two tertiary neonatal intensive care units. All neonates who underwent Targeted Neonatal Echocardiographic(TnECHO) assessments over May 2014-May 2017 were assessed for eligibility. Neonates whose echocardiography revealed a complete, measurableTR jet were included. Baseline characteristics such as gestational age, chronological age at echo, weight, blood pressure, ventilation and diagnosis were collected. Echocardiographic parameters such as TR Vmax, Pulmonary artery doppler waveform parameters such as Right Ventricular Ejection Time (RVET) and Pulmonary Artery Acceleration Time (PAAT) were measured by a single expert operator. Pulmonary Vascular Resistance Index (PVRI) was calculated as a ratio between RVET and PAAT. Correlation between pulmonary artery waveforms and RVSP estimated from the TR jet was examined using Pearson or Spearman analysis as appropriate. Univariate and multivariate regression analysis was used to further explore the influence of relevant factors on this relationship. Ethical approval was obtained from the institutional ethic board. RESULTS 678 neonates with 1767 echocardiographic studies were screened for eligibility of which 201 scans were included. Mean gestational age of this cohort was 30.5+/-5.7 weeks with mean birthweight of 1635 +/-1115 grams. Pulmonary Vascular Resistance Index (ratio of RVET to PAAT) also known as indexed PAAT, measured by Pulsed Wave Doppler at the level of the main pulmonary artery was found to have the strongest correlation with RVSP estimated from TRVmax. [r=0.45,P&lt;0.05]. Using regression analysis, we could generate an equation to estimate systolic pulmonary artery pressures(ESPAP) directly from PVRI. [ESPAP= 25.53 + 3.97xPVRI, p&lt;0.0001]. At the multivariate level, factors such as the Systolic Blood Pressure at time of echocardiogram and the presence or absence of PDA were found to have a statistically significance influence on this relationship. Pulmonary Vascular Resistance Index could be measured on all eligible scans. Inter-observer and intra-observer reliability assessment completed on a random subset of 30 showed excellent reliability for PVRI. [ICC =0.88, P&lt;0.000] CONCLUSION This important validation study shows that PAAT indexed to right ventricular ejection time(PVRI) has statistically significant correlation with pulmonary pressures as measured by TR jet in neonates. However the strength of correlation in neonates is moderate at best. The measurement is feasible with good interobserver agreement and potentially can play an important role in serial monitoring of pulmonary pressures in neonates without any demonstrable TR jet on echocardiography.

Hypertension pulmonaire et connectivites

Pulmonary hypertension (PH) is a rare complication of connective tissue diseases (CTD), and especially of systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). It is defined by an elevation of mean pulmonary arterial pressure above 25mmHg documented during a right-heart catheterization. Due to their systemic nature, CTD can induce PH by several mechanisms, that are sometimes intricated: pulmonary arterial (group 1) or venous (groupe 1′) microangiopathy, left-heart disease (group 2), chronic lung disease (group 3) and/or chronic thromboembolic disease (group 4). PH suspicion is often raised by echocardiographic data (which can show an elevation of the tricuspid regurgitation jet and/or a right atrial dilation), and/or by an isolated decrease in DLCO observed during pulmonary function tests, an unexplained elevation of serum NT-pro-BNP or right-heart abnormalities on an electrocardiogram. Its formal diagnosis always requires a hemodynamic confirmation by right-heart catheterization. Therapeutic management of PH depends of the underlying mechanism(s): pulmonary vasodilators in group 1 PH (with possible use of immunosuppressants in case of SLE or MCTD); management of an underlying left-heart disease in group 2 PH; management of an underlying chronic lung disease in group 3 PH; anticoagulation, pulmonary vasodilators, pulmonary endartectomy or balloon pulmonary angioplasty in group 4 PH. Regular follow-up is mandatory in patients with PH and CTD.

The obesity paradox: the protective effect of obesity on right ventricular function using echocardiographic strain imaging in patients with pulmonary hypertension

Obesity is associated with right ventricular (RV) dysfunction, but its effect on RV remodeling in patients with pulmonary hypertension (PHTN) has not been studied. We evaluated the effect of obesity, and its interplay with diabetes, in patients with PHTN using RV echocardiographic strain imaging. One hundred eighty-five patients underwent echocardiographic imaging and pulmonary artery pressure was calculated using tricuspid regurgitation jet velocity. From focused RV apical-four-chamber view, global and mid peak systolic RV free wall longitudinal strain (FWLS) was calculated using speckle-tracking software. Global and mid RV FWLS in patients with PHTN (N.=84) was lower (-16.8±7 vs. 18.9±6.3, P=0.035 and -11.2±12.8 vs. -18.9±9.2, P=0.002 respectively) compared with patients without PHTN (N.=101). Among patients without PHTN, obese patients (BMI>30) had lower global and mid RV FWLS (-17.2±6.2 vs. -20.3±5.7, P=0.012 and -17.6±7.2 vs. -21.9±7.3, P=0.004), even after excluding diabetic patients (Mid RV FWLS -18.2±6.8 vs. -22.1±8, P=0.032). Among patients with PHTN, obese patients had similar RV FWLS compared with non-obese patients (P=0.46). However, on excluding diabetic patients from PHTN group, obese patients with PHTN had higher global and mid RV FWLS (-21.7±5.7 vs. -16.1±8, P=0.017 and 23.8±4.8 vs. -17±9.4, P=0.009 respectively) compared to non-obese patients which suggests a protective effect of obesity on RV function in patients with PHTN. Obesity is associated with subclinical RV dysfunction as assessed by RV strain imaging, but paradoxically it may confer a protective effect on RV function once the patient develops PHTN. Future studies should evaluate the clinical impact of this paradox.

Abstract P331: Association of Extraosseous Calcification With Pulmonary Hypertension in Patients Evaluated for Kidney Transplantation

Background: Pulmonary hypertension (PH) is commonly reported in patients with end-stage renal disease (ESRD), and is associated with early graft failure and death in kidney transplant recipients. Calcifications of the lung, pulmonary vessels, heart, and kidney are frequently observed with ESRD, the consequence of secondary hyperparathyroidism. It follows that pulmonary artery vasculopathy, notably from extraosseous calcification, may contribute to PH. A popular, but unestablished, theory is that the stiffened pulmonary artery is unable to accommodate elevations in right ventricular stroke volume caused by arteriovenous (AV) hemodialysis shunts. We hypothesized that extraosseous calcification is related to PH in patients evaluated for kidney transplantation, and that the association is largely driven by AV shunts. Methods: Established in 2006, the UNC Cardiorenal Registry offers ongoing enrollment to all patients with stage 4 or 5 chronic kidney disease (CKD) referred for pretransplant cardiac evaluation. Pulmonary artery systolic pressure (PASP) was derived from routine echocardiograms within 6 months of the registry visit. All echocardiograms followed a standardized protocol, and were interpreted by the same cardiologist. PH was defined by a tricuspid regurgitant jet velocity &gt;2.8 m/s, corresponding to a PASP &gt;40 mmHg. Classification of grade 2 diastolic dysfunction (impaired left ventricular relaxation with elevated left atrial pressure) required a transmitral E/A ratio ≥ 0.8, and a transmitral to myocardial relaxation E/e’ ratio ≥ 15. Mitral annular calcification (MAC) was visually assessed, and considered evidence of extraosseous calcification. Associations between MAC and PH were analyzed with logistic regression, adjusted for age, sex, BMI, diastolic dysfunction, mitral regurgitation, left atrial dilation, and hematocrit. Results: From 2006-2013, 795 registry patients were screened preoperatively by echocardiography. Most were male (56%) and black (61%) with a mean age of 56 years. The majority (74%) received dialysis (13% peritoneal, 61% hemodialysis), for an average 2.8 years prior to the registry visit. PH, MAC, and AV shunts were present in 17%, 28%, and 62%; respectively. Relative to patients without MAC, those with MAC had higher odds of PH (OR adj =1.80; 95% CI: 1.17 – 2.78), which was not impacted by adjustment for AV shunts (OR adj = 1.78; 95% CI: 1.15 – 2.76). Further adjustment for years of dialysis modestly attenuated the association (OR adj = 1.55; 95% CI: 0.99 – 2.43). Conclusion: MAC is associated with higher odds of PH in severe CKD, irrespective of factors associated with PASP in the general population (age, sex, BMI), sources of pulmonary congestion (diastolic dysfunction, mitral regurgitation, and left atrial dilation), and causes of hyperdynamic circulation (hematocrit). The association is independent of hemodialysis shunts and dialysis vintage.

Diminished Cardiac Performance and Left Ventricular Dimensions in Neonates with Congenital Diaphragmatic Hernia.

Newborns with congenital diaphragmatic hernia (CDH) have varying degrees of pulmonary hypoplasia and pulmonary hypertension (PH), and there is limited evidence that cardiac dysfunction is present. We sought to study early neonatal biventricular function and performance in these patients by reviewing early post-natal echocardiography (ECHO) measurements and comparing them to normal term newborns. Retrospective case-control study reviewing clinical and ECHO data on term newborns with CDH and normal controls born between 2009 and 2016. Patients were excluded if major anomalies, genetic syndromes, or no ECHO available. PH was assessed by ductal shunting and tricuspid regurgitant jet velocity. Speckle-tracking echocardiography was used to assess myocardial deformation using velocity vector imaging. Forty-four patients with CDH and 18 age-matched controls were analyzed. Pulmonary pressures were significantly higher in the CDH cohort (systolic pulmonary arterial pressure to systolic blood pressure of 103 ± 13 vs. 78 ± 29%, p = 0.0001). CDH patients had decreased RV fractional area change (FAC - 28.6 ± 11.1 vs. 36.2 ± 9.6%, p = 0.02), tricuspid annular plane of systolic excursion (TAPSE-5.6 ± 1.6 vs. 8.6 ± 1.6mm, p = 0.0001), and RV outflow tract stroke distance (8.6 ± 2.7 vs. 14.0 ± 4.5cm, p = 0.0001) compared with controls. The left ventricular (LV) ejection fraction was similar in both groups, but CDH patients had a decreased LV end-diastolic volume by Simpson's rule (2.7 ± 1.0 vs. 5.0 ± 1.8mL, p = 0.0001) and LVOT stroke distance (9.7 ± 3.4 vs. 12.6 ± 3.6cm, p = 0.004). Biventricular global longitudinal strain (GLS) was markedly decreased in the CDH population compared to controls (RV-GLS: - 9.0 ± 5.3 vs. - 19.5 ± 1.4%, p = 0.0001; LV GLS: - 13.2 ± 5.8 vs. - 20.8 ± 3.5%, p = 0.0001). CDH newborns have evidence of biventricular dysfunction and decreased cardiac output. Abnormal function may be a factor in the non-response to pulmonary arterial vasodilators in CDH patients. A two-pronged management strategy aimed at improving cardiac function, as well as reducing pulmonary artery pressure in CDH newborns, may be warranted.

Tricuspid annular plane systolic excursion-to-aortic ratio provides a bodyweight-independent measure of right ventricular systolic function in dogs

ObjectivesTo evaluate whether tricuspid annular plane systolic excursion (TAPSE) can be normalized to aortic valve (Ao) measurements in dogs. To determine TAPSE:Ao reference intervals for healthy dogs and examine diagnostic performance of TAPSE:Ao in dogs with pulmonary hypertension (PH). AnimalsOne hundred and thirty-seven healthy adult dogs; 115 dogs with myxomatous mitral valve disease (MMVD) but no PH; 91 dogs with PH. MethodsA combined prospective and retrospective study. Full echocardiographic evaluations were performed on all dogs; TAPSE was indexed to Ao to produce a unitless TAPSE:Ao. Reference intervals for TAPSE:Ao were generated, and TAPSE:Ao was regressed on tricuspid regurgitant jet velocity in dogs with PH and on LA:Ao in dogs with MMVD without PH. Diagnostic test analysis was used to examine the ability of TAPSE:Ao to identify severe PH. An adjusted TAPSE:Ao (TAPSE:Ao(adj)) was derived to account for MMVD in dogs with PH. ResultsThe ratio, TAPSE:Ao, removed the effect of bodyweight from TAPSE measurements. Healthy dogs had TAPSE:Ao > 0.65. The ratio, TAPSE:Ao, showed a linear negative relationship with tricuspid regurgitation velocity and positive relationship with LA:Ao. The adjusted ratio, TAPSE:Ao(adj), increased the sensitivity of diagnosis of PH in dogs with moderate-severe MMVD without affecting the diagnosis of PH in dogs with PH and with no or mild MMVD. ConclusionsThe ratios, TAPSE:Ao and TAPSE:Ao(adj), are a bodyweight-independent means of assessing right ventricular systolic function in dogs and for identifying severe PH in dogs with or without MMVD.

Reappraisal of the reliability of Doppler echocardiographic estimations for mean pulmonary artery pressure in patients with pulmonary hypertension: a study from a tertiary centre comparing four formulae.

Different Doppler echocardiography (DE) models have been proposed for estimation of mean pulmonary arterial pressures (PAMP) from tricuspid regurgitation (TR) jet velocity. We aimed to compare four TR-derived DE models in predicting the PAMP measured by right heart catheterization (RHC) in different groups of precapillary pulmonary hypertension (PH). A total of 287 patients with hemodynamically pre-capillary PH were enrolled (mean age = 51 ± 17.4 years, 59.9% female). All patients underwent DE before RHC (< 3 h) and four formulae (F) were used for TR-derived PAMP estimation (PAMP-DE). These were as follows: F1 = Chemla (0.61 × systolic pulmonary artery pressure [PASP] + 2); F2 = Friedberg (0.69 × PASP − 0.22), F3 = Aduen (0.70 × PASP); and F4 = Bech-Hanssen (0.65 × PASP − 1.2). The PASP and PAMP (mmHg) measured by RHC were 89.1 ± 30.4 and 55.8 ± 20.8, respectively. In the overall PH group, DE estimates for PASP (r = 0.59, P = 0.001) and PAMP (r = 0.56, P = 0.001 for all) showed significant correlations with corresponding RHC measures. Concordance was noted between Chemla and Bech-Hanssen, and Aduen and Bech-Hanssen. The Bland–Altman plot showed that Chemla and Bech-Hanssen overestimated and Friedberg and Aduen underestimated PAMP-RHC measures. Paired-t test showed significant systematic biases for Aduen and Bech-Hanssen while Passing-Bablok non-parametric analysis revealed significant systematic biases all four PAMP-DE estimates. There was poor agreement between PAMP-RHC measures and PAMP-DE deciles (Kappa values were 0.112, 0.097, 0.095, and 0.121, respectively). This study showed a poor agreement between PAMP-DE estimates by four TR-derived formulae and PAMP-RHC in patients with PH, regardless of the etiology. However, these results can not be fully extrapolated to a normal population and did not address the reliability of DE estimates for PH screening procedures.

Lower than expected elevated tricuspid regurgitant jet velocity in adults with sickle cell disease in Nigeria.

Cardiopulmonary disease is a major cause of morbidity and mortality in persons with sickle cell disease (SCD). Tricuspid regurgitant jet velocity (TRJV) and predicted forced expiratory volume in 1 s (FEV1%) predicted are independently associated with death in SCD. The goal of this study was to determine the prevalence of elevated TRJV and the association, if any, between TRJV and FEV1% predicted among persons with sickle cell anaemia (SCA) in Nigeria. Using a cross-sectional design, we enrolled 100 adult Nigerians (≥15 y) with SCA. We screened participants using Doppler echocardiogram to determine their TRJV and assessed their lung function with spirometry. The prevalence of elevated TRJV was 6%, with 74% of participants having low FEV1% predicted (<70%). TRJV was negatively correlated with FEV1%, but this finding was not statistically significant (Spearman's ρ=-0.0263, p=0.8058). We found a low prevalence of elevated TRJV and a trend in association between TRJV and FEV1% predicted in Nigerian adults with SCA. Our findings underscore the need to explore further the relationship between SCD and cardiopulmonary disease in adults.

89: Fetal endoscopic tracheal occlusion (FETO) reduces pulmonary hypertension in severe congenital diaphragmatic hernia (CDH)

Growing evidence indicates fetal endoscopic tracheal occlusion (FETO) improves perinatal survival in fetuses with severe congenital diaphragmatic hernia (CDH).This study evaluates the impact of FETO on the resolution of pulmonary hypertension (PH) in fetuses with isolated severe left or right-sided CDH. All fetuses evaluated for CDH between January 2004 and July 2017 at a single institution were included. The resolution of PH by 1 year of life was compared in a cohort of infants with severe CDH who underwent FETO to a non-FETO cohort. The non-FETO cohort included CDH neonates stratified by prenatal MRI severity indices, [observed to expected total lung volume (O/E TLV) and % liver herniation] into mild, moderate, and severe groups. Postnatal echocardiograms were used to determine presence of PH, defined as elevation of pulmonary arterial pressure > 2/3 systemic systolic pressure based on Doppler parameters of the ductus arteriosus, interventicular septal position, and/or peak tricuspid regurgitant jet velocity. Patients were included if they underwent at least one prenatal MRI, had serial echocardiograms (the first within 48 hours of life) and had no other major structural or chromosomal anomalies. ANOVA and Dunnett’s post hoc tests were used for comparisons. A total of 254 CDH cases were evaluated; 57% (n=145) had no major structural or chromosomal anomalies and 106 met inclusion criteria. The FETO cohort consisted of 18 severe CHD cases and the non-FETO cohort consisted of 35% mild (n=31), 36% moderate (n=32), 29% severe (n=25) CHD cases. The proportion of left-or right-sided CDH cases was not different among groups. All infants with severe CDH, with and without FETO, had evidence of neonatal PH (see Table). By 1 year of life, a higher proportion of infants with severe CDH who underwent FETO had resolution of PH compared to infants with severe CDH in the non-FETO cohort (66.7% vs. 28%; p: 0.021). Of note, this proportion was similar to that of the moderate cases in the non-FETO cohort (see Table). FETO was also associated with a reduced need for ECMO in severe CHD cases regardless of the site of the CDH lesion (p: 0.009). In severe CDH infants, FETO is associated with resolution of PH by 1 year of life akin to moderate CDH cases. FETO may induce changes in fetal lung architecture facilitating resolution of PH in severe CDH.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Predictive value of pulmonary function testing in the evaluation of pulmonary hypertension in sarcoidosis.

Background: In sarcoidosis patients, pulmonary hypertension (PH) is associated with significant morbidity and mortality. Early identification of sarcoidosis-associated pulmonary hypertension (SAPH) has substantial clinical implications. While a number of pulmonary function testing (PFT) variables have been associated with SAPH, the optimal use of PFT’s in screening for SAPH is unknown. Objectives: To examine the predictive value of PFT’s for echocardiographic PH in a cohort of sarcoidosis patients. Methods: We conducted a retrospective cohort study of patients with sarcoidosis from a single center over a period of five years. All consecutive adult patients with a diagnosis of biopsy-proven sarcoidosis (determined by review of the medical chart) who underwent PFT and echocardiographic testing were included. Echocardiographic risk of PH (either intermediate or high) was determined by the presence of echocardiographic PH signs and tricuspid regurgitant jet velocity. Data analysis was performed using multivariate logistic regression analysis with least absolute shrinkage and selection operator. Results: Of the 156 patients included in the study, 42 (27%) met the criteria for echocardiographic PH. Roughly equal proportions met the criteria for intermediate risk (45%) as did for high risk of PH (55%). The percent predicted of diffusion capacity for carbon monoxide (%DLCO) and forced vital capacity (%FVC) were predictive of echocardiographic PH. No other PFT variables outperformed these two markers, and the incorporation of additional PFT variables failed to significantly enhance the model. Conclusions: The %FVC and %DLCO emerged as being predictive of echocardiographic PH in this cohort of biopsy-proven sarcoidosis patients. Potentially reflecting the multifactorial pathogenesis of PH in sarcoidosis, incorporation of other PFT variables failed to enhance screening for PH in this population. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 308-316)

Successful Plerixafor-Mediated Mobilization, Apheresis, and Lentiviral Vector Transduction of Hematopoietic Stem Cells in Patients with Severe Sickle Cell Disease

Background Patients with severe sickle cell disease (SCD) may benefit from β-globin gene transfer into autologous hematopoietic stem cells (HSC). Successful HBB gene transfer requires vector-mediated transduction of primitive HSCs. Steady-state bone marrow (BM) is the default HSC source in patients with SCD. Normal human BM contains up to 30% CD34+CD19+ pro-B cells and other lineage-committed cell types (CD34dim) that will not contribute to improved long-term erythropoiesis via gene therapy; these cells mobilize at low rates. CD34+ cell yields from BM harvest (BMH) are typically lower than those after mobilization and peripheral blood (PB) apheresis; multiple rounds of BMH may be required to obtain adequate cell doses for autologous gene therapy (GT) protocols. As G-CSF can cause life-threatening SCD complications and is contraindicated, plerixafor, a CXCR4 receptor antagonist, may accomplish HSC mobilization without the neutrophil or endothelial activation that elicit vaso-occlusion. We modified the protocol for the HGB-206 phase 1 study of LentiGlobin GT in severe SCD (NCT02140554) to assess HSC mobilization with plerixafor alone, followed by apheresis and transduction of mobilized cells. We also characterized BM-derived and plerixafor-mobilized HSC populations from patients with SCD. Methods HGB-206 is a phase 1 study of LentiGlobin Drug Product (DP), which contains autologous HSCs transduced ex vivo with the betibeglogene darolentivec (BB305) lentiviral vector, in patients with severe SCD (defined as a history of recurrent vaso-occlusive crisis [VOC], acute chest syndrome, stroke, or tricuspid regurgitant jet velocity of >2.5 m/s). Patients in group B receive 240 µg/kg plerixafor followed 4-6 hours later by apheresis, processing ~3 total blood volumes to collect backup HSCs. If Results To date, 3 patients have undergone plerixafor mobilization. Patients had a transient 1.5- to 3-fold increase in peak white blood cell and absolute neutrophil levels after plerixafor. Peak absolute CD34+ cell counts in PB were 170, 58, and 160 x 106 CD34+ cells/liter. A total of 15.3, 5.6, and 9.0 x 106 CD34+ cells/kg were collected in a single day of apheresis, and no subsequent apheresis or mobilization was required. In the same study, a mean of 5.0 (range 0.3-10.8) x 106 CD34+ cells/kg were collected per BMH (N=21). The mobilization and apheresis procedures had an acceptable toxicity profile. No dose-limiting toxicities were observed after plerixafor dosing. One patient had a single VOC approximately 48 hours after receiving plerixafor; this patient also experienced VOCs of similar severity after BMH. In contrast, after 21 BMHs in 9 patients, 18 ≥ grade 3 AEs were reported in 6 patients, primarily pain. Ex vivo cultured CD34+ cells isolated from BMH consisted of an average of 41.0% (17.3%-50.7%) CD34dim cells, with 16%-50% of the CD34dim cells expressing lymphoid markers. In contrast, ex vivo cultured CD34+ cells isolated from plerixafor mobilized PB contained an average of 8.2% (1.5-19.5%) CD34dim cells. Similar drug product vector copy numbers were obtained after research-scale transduction of CD34+ cells from marrow and PB from the same patient. Conclusion Initial results suggest that obtaining adequate doses of CD34+ cells from plerixafor-mobilized PB of patients with SCD may be safe and feasible, without the life-threatening complications associated with G-CSF, and with fewer, less invasive procedures compared with BMH. PB-derived CD34+ cells may contain lower proportions of lineage-committed CD34+ cells than BM-derived cells from patients with SCD. Cells collected by BMH and PB mobilization/apheresis appear to have an equivalent transduction efficiency. Together these results indicate that it may be possible to use plerixafor-only mobilization in clinical studies of autologous HSC GT in SCD. Results of mobilization, apheresis, and DP manufacturing at clinical scale for additional patients will be available for presentation. Disclosures Pierciey: bluebird bio: Employment. Kanter: American Society of Hematology (Sickle Cell Disease Guideline Panel): Membership on an entity9s Board of Directors or advisory committees; AstraZeneca: Membership on an entity9s Board of Directors or advisory committees; Novartis: Membership on an entity9s Board of Directors or advisory committees, Research Funding; MUSC: Other: The site PI for sponsored research conducted at MUSC who receives funds from: Novartis, bluebird bio, GBT, Sancillo, Apopharma, Pfizer; NHLBI (sickle cell disease research advisory committee): Membership on an entity9s Board of Directors or advisory committees, Research Funding; Sancillo: Research Funding; Apopharma: Research Funding; Pfizer: Research Funding; GBT: Research Funding; Bluebird Bio: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Kwiatkowski: Novartis: Research Funding; Bluebird Bio: Research Funding; Apopharma: Research Funding; Agios: Consultancy, Honoraria; Ionis: Consultancy, Honoraria. Thompson: Novartis: Consultancy, Research Funding; bluebird bio: Consultancy, Research Funding; Baxalta: Research Funding; Celgene: Consultancy, Research Funding. Shestopalov: bluebird bio: Employment, Equity Ownership. Bonner: bluebird bio: Employment, Equity Ownership. Joseney-Antoine: bluebird bio: Employment, Equity Ownership. Asmal: bluebird bio: Employment, Equity Ownership. Walters: bluebird bio: Research Funding; ViaCord Processing Lab: Other: Medical Director; Sangamo Therapeutics: Consultancy; AllCells, Inc: Other: Medical Director.