Higher Pulmonary Vascular Resistance Index Research Articles

Sex Differences in Outcomes of Adults With Isolated Coarctation of the Aorta

BackgroundData are limited about the effect (or lack thereof) of sex on clinical outcomes in adults with coarctation of the aorta (COA). The purpose of this study was to compare atherosclerotic cardiovascular disease (ASCVD) risk profile, blood pressure (BP) data, echocardiographic indices, and mortality between men and women with COA. MethodsRetrospective study of adults with COA, and no associated left-sided obstructive lesions, who received care at Mayo Clinic (2003-2022). ASCVD risk profile was assessed as the prevalence of hypertension, hyperlipidemia, type 2 diabetes, obesity, smoking history, and coronary artery disease. A 24-hour BP monitor was used to assess daytime and nighttime BP and calculate nocturnal dipping. ResultsOf 621 patients with isolated COA, 375 (60%) were men, and 246 (40%) were women. Women had similar ASCVD risk profile and daytime BP as men. However, women had less nocturnal dipping (7 ± 5 mm Hg vs 16 ± 7 mm Hg, P < 0.001), higher pulmonary artery mean pressure (23 mm Hg [range: 16-31] vs 20 mm Hg [range: 15-28], P = 0.04), and higher pulmonary vascular resistance index (3.41 ± 1.14 WU · m2 vs 3.02 ± 0.76 WU · m2, P = 0.006). Female sex was associated with all-cause mortality (adjusted hazard ratio 1.26, 95% confidence interval 1.04-1.94) and cardiovascular mortality (adjusted hazard ratio 1.38, 95% confidence interval 1.09-2.18). ConclusionsWomen had a higher risk of both cardiovascular mortality and all-cause mortality compared to the risks in men. This difference may be related to the higher-than-expected ASCVD risk factors, abnormal nocturnal blood pressure, and pulmonary hypertension observed in women in this cohort. Further studies are required to identify optimal measures to address these risk factors.

Effects of ventricular assist device with a fenestration in the failing Fontan circulation: a theoretical analysis using a lumped parameter model

Abstract Background Fenestration is surgically created at the time of Fontan operation, in which the extracardiac conduit is connected to the atrium through a small communication. Since the fenestration has been reported to increase venous return to the ventricle and improve the hemodynamics, the fenestration is often made when the risk of postoperative Fontan failure is high. In the failing Fontan circulation, the implantation of ventricular assist device (VAD) is sometimes required as a bridge-to-transplantation therapy. However, it has been controversial whether a closure of fenestration is necessary or not. Purpose To evaluate the effects of fenestration on the hemodynamics under VAD in the failing Fontan circulation. Methods A computational model of Fontan circulation was developed using a time-varying elastance cardiac chamber model and a modified 3-element Windkessel vasculature model. Pressure gradient through fenestration was calculated by the simplified Bernoulli’s equation. The relationship between pressure head and rotational frequency of VAD was modeled as a non-linear function. To simulate Fontan failure, ventricular end-systolic elastance was set at 1.0 mmHg/ml and then pulmonary vascular resistance index (PVRI) was varied from 3.0 to 6.8 WU m². Results In the Fontan failure model with PVRI of 3.0 WU m², mean blood pressure (MBP), cardiac index (CI) and central venous pressure (CVP) were 58.4 mmHg, 1.7 l/min/m² and 19.2 mmHg, respectively. When MBP was maintained at the same value, the 4-mm fenestration rarely affected CI (1.7 l/min/m²) and CVP (18.1 mmHg), but significantly decreased oxygen saturation (SpO2, 84.0 %). The introduction of VAD at 4000 rpm significantly increased MBP and CI in both models with/without fenestration (Fenestration (+): 93.7 mmHg, 3.2 l/min/m², Fenestration (-): 94.5 mmHg, 3.2 l/min/m²). In the model with fenestration, SpO2 recovered to 91.6 % after the VAD initiation. However, CVP slightly changed after the VAD initiation in both models with/without fenestration (18.5 and 18.9 mmHg, respectively). When stressed blood volume (SBV) was decreased until end-systolic ventricular volume became around 0 ml, CVP was decreased to the normal range (Fenestration (+): 8.3 mmHg, Fenestration (-): 10.0 mmHg). Then SBV was significantly lower in the model with fenestration than that without fenestration (-150 ml). The effects of fenestration on CVP and SBV were larger in the model with high PVRI of 6.8 WU m² (CVP: -5.5 mmHg, SBV: -460 ml) than those with PVRI of 3.0 WU m² (CVP: -1.7 mmHg, SBV: -150 ml). Conclusions Although fenestration decreases SpO2 at the onset of Fontan failure, fenestration can significantly decrease CVP and SBV under VAD support. These effects are more significant in the patients with higher PVRI. This study demonstrates that fenestration did not impair the hemodynamics under VAD support, indicating the closure of fenestration may not be necessary.

Echocardiography Assessment of Left Ventricular Function in Extremely Preterm Infants, Born at Less Than 28 Weeks’ Gestation, With Bronchopulmonary Dysplasia and Systemic Hypertension

The survival of smaller and more immature premature infants has been associated with lifelong cardiorespiratory comorbidities. Infants with bronchopulmonary dysplasia (BPD) undergo routine screening echocardiography to evaluate for development of chronic pulmonary hypertension, a late manifestation of pulmonary vascular disease. Our aim was to evaluate left ventricular (LV) performance in infants with BPD and pulmonary vascular disease who developed systemic hypertension. We hypothesized that infants with hypertension were more likely to have impaired LV performance. We present a single-center cross-sectional study of premature infants born at less than 28 0/7weeks'gestational age with a clinical diagnosis of BPD. Infants were categorized by the systolic arterial pressure (SAP) at time of echocardiography as hypertensive (SAP ≥90mm Hg) or normotensive (SAP <90mm Hg). Sixty-four patients were included. Infants with hypertension showed altered LV diastolic function with prolonged tissue Doppler imaging-derived isovolumic relaxation time (54.2±5.1 vs 42.9±8.2, P<.001), lower E:A, and higher E:e'. Indices of left heart volume/pressure loading (left atrium:aorta and LV end-diastolic volume [6.1±2 vs 4.2±1.2, P<.001]) were also higher in the hypertensive group. Finally, infants in the hypertensive group had higher pulmonary vascular resistance index (4.42±1.1 vs 3.69±0.8, P=.004). We conclude that extremely preterm infants with BPD who develop systemic hypertension are at risk of abnormal LV diastolic dysfunction. Increased pulmonary vascular resistance index in the hypertensive group may relate to pulmonary venous hypertension secondary to LV dysfunction. This is an important consideration in this cohort when selecting the physiologically most appropriate treatment.

Long-term outcome of children with newly diagnosed pulmonary arterial hypertension: results from the global TOPP registry.

The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global network established to gain insights into the disease course and long-term outcomes of paediatric pulmonary arterial hypertension (PAH). Previously published cohorts in paediatric PAH are obscured by survival bias due to the inclusion of both prevalent (previously diagnosed) and incident (newly diagnosed) patients. The current study aims to describe long-term outcome and its predictors in paediatric PAH, exclusively of newly diagnosed patients. Five hundred thirty-one children with confirmed pulmonary hypertension, aged ≥3 months and <18 years, were enrolled in the real-world TOPP registry at 33 centres in 20 countries, from 2008 to 2015. Of these, 242 children with newly diagnosed PAH with at least one follow-up visit were included in the current outcome analyses. During long-term follow-up, 42 (17.4%) children died, 9 (3.7%) underwent lung transplantation, 3 (1.2%) atrial septostomy, and 9 (3.7%) Potts shunt palliation (event rates: 6.2, 1.3, 0.4, and 1.4 events per 100 person-years, respectively). One-, three-, and five-year survival free from adverse outcome was 83.9%, 75.2%, and 71.8%, respectively.Overall, children with open (unrepaired or residual) cardiac shunts had the best survival rates. Younger age, worse World Health Organization functional class, and higher pulmonary vascular resistance index were identified as independent predictors of long-term adverse outcome. Younger age, higher mean right atrial pressure, and lower systemic venous oxygen saturation were specifically identified as independent predictors of early adverse outcome (within 12 months after enrolment). This comprehensive analysis of survival from time of diagnosis in a large exclusive cohort of children newly diagnosed with PAH describes current-era outcome and its predictors.

LACK OF PULMONARY HYPERTENSION REGRESSION IN PATIENTS WITH SEVERE AORTIC STENOSIS ASSOCIATED WITH CHRONIC LUNG DISEASE AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT

LACK OF PULMONARY HYPERTENSION REGRESSION IN PATIENTS WITH SEVERE AORTIC STENOSIS ASSOCIATED WITH CHRONIC LUNG DISEASE AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT

Preoperative N-terminal pro-brain natriuretic peptide is associated with Fontan outcomes

ObjectiveThe role of preoperative N-terminal pro-brain natriuretic peptide level in patient outcomes after the Fontan operation remains unclear. MethodsThe medical records of all patients who underwent their first Fontan operation from June 2011 to October 2019 in our tertiary referral pediatric cardiac center were retrospectively reviewed. Preoperative hemodynamic factors and N-terminal pro-brain natriuretic peptide were analyzed to test the association of mortality and morbidity. ResultsWe enrolled 110 patients (men/women 62/48; median age, 4.1 [3.4, 5.8] years; median follow-up period, 4.28 [2.31, 6.71] years). Almost all operations were extracardiac conduits (98.2%). Primary outcomes of death, Fontan takedown, and heart transplantation were observed in 9 patients (8.2%). Abnormal ventricular contractility, elevated preoperative pulmonary artery pressure, high pulmonary vascular resistance index, and high log10 N-terminal pro-brain natriuretic peptide level were associated with poor outcomes. Secondary outcomes: atrioventricular valve regurgitation moderate or greater, elevated pulmonary artery pressure, high pulmonary vascular resistance index, and high log10 N-terminal pro-brain natriuretic peptide level were associated with rehospitalization due to heart failure. Multivariable Cox regression analysis revealed that log10 N-terminal pro-brain natriuretic peptide was the only significant predictor of all primary and secondary outcomes. A scoring system including factors of pulmonary artery pressure, pulmonary vascular resistance index, and N-terminal pro-brain natriuretic peptide was established, and the risk stratification is associated with outcomes after the Fontan operation. ConclusionsHigh preoperative N-terminal pro-brain natriuretic peptide was associated with poor outcomes after the Fontan operation.

Prognostic Value of Early Risk Stratification in Pediatric Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease with risk stratification-based treatment strategy in adults. Although the risk factors have been studied individually in children, effective risk stratification is still lacking. We have tested the prognostic accuracy of pediatric PAH risk factors in our patient group. Records of 58 PAH patients treated between 1995 and 2019 were reviewed retrospectively. Median age at diagnosis was 4.2 years (range, 0.1-16.1 years), and follow-up was 5.4 years (range, 0.01-24.1 years). Data collected at diagnosis were demographics, World Health Organization functional class, evidence of right ventricular failure, and parameters of echocardiography and cardiac catheterization. Mortality was 29% and 33% reached the composite endpoint. Patients with idiopathic PAH (n=12) had increased risk of mortality compared with the congenital heart disease-associated PAH group (n=32) (P=.0024). Neither the initial World Health Organization functional class staging nor the echocardiographic parameters significantly predicted the prognosis. The number of risk factors had no significant prognostic value either. In contrast, patients with higher pulmonary vascular resistance index (PVRI) had significantly increased risk (each 10 Wood units ⋅ m2 increase in PVRI being associated with 49.1% higher hazard, P=.0048). Survival analysis showed that PAH etiology might be an important determinant in pediatric PAH risk stratification. We confirmed that PVRI has predictive value in prognostic assessment. We could not establish the prognostic value of nonweighted single risk factors or their combination to predict pediatric PAH outcome due to the low sample size, but these results indicate that such studies are warranted.

ST2 Is a Biomarker of Pediatric Pulmonary Arterial Hypertension Severity and Clinical Worsening

Pediatric pulmonary hypertension is a severe disease defined by sustained elevation of pulmonary artery pressures and pulmonary vascular resistance (PVR). Noninvasive diagnostic and prognostic markers that are more pulmonary vascular specific have been elusive because of disease heterogeneity and patient growth. Is soluble suppressor of tumorigenicity (ST2) associated with pulmonary hemodynamic and functional changes in pediatric pulmonary hypertension? Does ST2 improve mortality risk models in pediatric pulmonary hypertension? Two pediatric cohorts (age< 21 years) were assayed for ST2 and N-terminal prohormone B-natriuretic peptide: a cross-sectional cohort from the National Heart Lung and Blood Institute-funded National Biological Sample and Data Repository for PAH (PAHB) (N= 182), and a second longitudinal cohort from Children's Hospital of Colorado (N= 61). Adjusted linear regression was used for association with clinical variables. Clinical mortality models (the Registry to Evaluate Early and Long-Term PAH Disease Management [REVEAL] score) with and without ST2 were used to predict worsening outcomes and compared. Pulmonary artery endothelial and smooth muscle cell ST2 expression and secretion were assayed invitro. In an adjusted (age and sex) analysis in the PAHB, ST2 was significantly associated with shorter 6-min walk distance (P= .03) and increased PVR index (P= .02). In adjusted longitudinal regression in the Children's Hospital of Colorado cohort, ST2 was significantly associated with higher PVR index (P< .001), shorter 6-min walk distance (P= .01), and higher mean pulmonary artery pressure (P< .001). Although the REVEAL Risk Score Calculator 2.0 was predictive of clinical worsening in the PAHB (hazard ratio, 1.88), addition of ST2 significantly improved the model (hazard ratio, 2.05). In cell culture, ST2 was produced and secreted predominately by endothelial cells as opposed to smooth muscle cells (P< .0001). In two pediatric PAH cohorts, elevated ST2 was associated with unfavorable pulmonary hemodynamics and functional measures, clinical worsening, and significantly improved prediction of clinical worsening. Pulmonary artery endothelial cellular expression of ST2 suggests that ST2 is a more pulmonary vascular-specific marker for pulmonary hypertension.

Degree of Portal and Systemic Hemodynamic Alterations Predict Recurrent AKI and Chronic Kidney Disease in Patients With Cirrhosis.

The relevance of hemodynamic derangements on the incidence of recurrent acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with cirrhosis is largely unknown. Consecutive patients with cirrhosis with a complete record of baseline hemodynamics were followed for identifying risk factors for the development of recurrent AKI and CKD by using negative binomial regression and competing risk analysis, respectively. Consecutive patients with cirrhosis (n = 2013, age 50.1 ± 11.8 years, 80% male, Child A:B:C percentage 13.7:52.9:33.4, and mean Child‐Turcotte‐Pugh score 8.6 ± 1.8) were enrolled, 893 (44.3%) of whom received beta‐blockers, with 44.2% responders. Prior AKI was noted in 12.4% at enrollment. At a median follow‐up of 379 (interquartile range: 68‐869) days, AKI developed at a rate of 0.37 episodes per person‐year, and 26% patients developed CKD. A lower mean number of AKI episodes (0.05 ± 0.25 vs. 0.42 ± 0.868; P < 0.001), CKD (subdistribution hazard ratio 0.74 [0.54‐1.02]), and mortality (hazard ratio 0.21 [0.06‐0.73]) were observed in beta‐blocker responders. Albuminuria was an independent risk factor for recurrent AKI, CKD, and mortality (P < 0.05). Lower systemic vascular resistance index predicted hemodynamic response (odds ratio 2.04 [1.29‐3.22]), cumulative AKI episodes (ratio of means 0.10 [0.08‐0.14]), and development of CKD (subdistribution hazard ratio 0.70 [0.58‐0.83]). Higher hepatic venous pressure gradient (≥17 mm Hg) predicted AKI episodes (ratio of means 1.76 [1.32‐2.35]) but not CKD. Conclusion: High portal pressure and severe vasodilatation predispose patients with cirrhosis to repeated AKI episodes and development of CKD. Response to beta‐blockers and therapies targeting the vasodilatory state could prevent frequent AKI and the risk of CKD development. Albuminuria could serve as an early marker of renal dysfunction in patients with cirrhosis.

Survival of Patients after Left-to-Right Shunt Repaired of Congenital Heart Defect: A Comparison between Baseline Pulmonary Vascular Resistances

Objective: This study compared the survival of patients with completely repaired pulmonary hypertension-associated congenital heart disease (PH-CHD) with a left-to-right shunt based on their pulmonary vascular resistance index (PVRi). Material and Methods: In this retrospective cohort study, the demographics, disease characteristics, laboratory tests, hemodynamic characteristics and survival of patients with PH-CHD in our institute between January 2004 and January 2016 were reviewed. Results: Of 298 patients, 216 had a low PVRi (72.5%), 57 had a moderate PVRi (19.1%) and 25 had a high PVRi (8.4%). In the overall population, the 1-, 5- and 10-year survival rates were 96.6±1.0%, 94.2±1.5%, and 91.1±3.3%, respectively. At 10 years after the operation, patients with a low PVRi had the best survival, but patients with a moderate PVRi didn’t have significantly better survival than the patients with a high PVRi (98.6±0.8% vs. 81.9±5.5% vs. 76.5±11.2%, respectively; p-value&lt;0.001 in low vs. moderate or high PVRi; p-value=0.8 in moderate vs. high PVRi). The World Health Organization functional class and PVRi were predictors of survival at 10 years after the operation. Conclusion: This study supports the recent 2015 European Society of Cardiology and European Respiratory Society guideline, which says that patients with a PVRi &lt;4 Wood units m2 have the best survival, a PVRi of 8 Wood units m2 was proposed as the limit for considering surgery, and a PVR of 4–8 Wood units m2 as the range in which the proper approach should be considered on a case by case basis.

Genotypes and Phenotypes of Chinese Pediatric Patients With Idiopathic and Heritable Pulmonary Arterial Hypertension—A Single-Center Study

BackgroundThe relationship between clinical outcomes and gene mutations in Chinese pediatric patients with idiopathic and heritable pulmonary arterial hypertension (PAH) is unclear. MethodsWe retrospectively studied the clinical characteristics and outcomes of pediatric patients who visited Beijing Anzhen Hospital from September 2008 to December 2018. ResultsEighty-two pediatric patients were included. Forty-two gene mutations were identified in 41 patients (50%), including 25 mutations in BMPR2, 5 mutations in ACVRL1, 3 mutations each in ABCA3 and NOTCH3, 2 mutations each in KCNK3 and HTR2B, 1 mutation in ENG, and 1 mutation in EIF2AK4. The mean age at diagnosis of PAH was 86.4 ± 55.1 months. Forty-eight patients (twenty-eight mutation carriers) underwent cardiac catheterization examinations, with acute vasodilator testing performed simultaneously. Results showed that mutation carriers demonstrated a higher pulmonary vascular resistance index (P = 0.037). Patients with gene mutations responded poorly to vasodilators (P = 0.001). The 1-, 2-, and 3-year survival rates of mutation noncarriers were 95.1%, 87.8%, and 82.5% respectively; while for mutation carriers, the proportions were 86.6% (P = 0.216), 63.8% (P = 0.021), and 52.2% (P = 0.010), respectively. Cardiac index was an independent predictor of death (P = 0.005; odds ratio [OR] 2.16, 95% confidence interval [CI] 1.258-3.704), as well as RAP (P = 0.01; OR 1.26, 95% CI 1.056-1.503). ConclusionsIn our cohort of Chinese pediatric patients, those with an identified gene mutation demonstrated worse clinical outcomes. Therefore, early gene screening for pediatric patients with idiopathic and heritable PAH is recommended, and more aggressive treatment for mutation carriers may be advisable.

Effective shunt closure for pulmonary hypertension and liver dysfunction in congenital portosystemic venous shunt.

Congenital portosystemic venous shunt (CPSVS) is a rare vascular malformation with a high risk of mortality from pulmonary arterial hypertension (PAH), but the treatment outcome of CPSVS closure remains elusive. Our aim was to investigate the clinical features and establish the optimal management of CPSVS with or without PAH. Twenty-four patients with CPSVS treated in Kyushu University Hospital between 1990 and 2015 were enrolled in this study. The patients were divided into a PAH group (n = 9) and a non-PAH group (n = 15). Clinical characteristics and outcomes were evaluated. The first manifestation of CPSVS at diagnosis (28.5 [1-216] months) was hypergalactosemia in 13 (54%) or PAH in six (25%) patients. PAH was the cause of all three deaths. The PAH group had higher levels of serum total bile acid, manganese, and total bilirubin, along with higher pulmonary vascular resistance index (PVRI) than the non-PAH group (7.2 [5.1-38.1] vs 1.2 [0.5-3.3] unit/m2 , P < 0.001). Five of nine PAH patients underwent CPSVS closure at a median of 38 months (range 21-118) after PAH diagnosis. Pulmonary artery pressure improved after CPSVS closure with PAH-specific therapy, but normal range was not achieved. CPSVS closure improved the hepatic synthetic function of four PAH patients. Eigh-t of 15 non-PAH patients who received CPSVS closure did not develop PAH for a median of 34.5 months (range 6-164) after the procedure. CPSVS closure with PAH-specific therapy successfully controlled PAH. Early CPSVS closure may prevent the occurrence and progression of PAH with CPSVS.

Hemodynamics of Fontan Failure: The Role of Pulmonary Vascular Disease.

Nonpulsatile pulmonary blood flow in Fontan circulation results in pulmonary vascular disease, but the potential relationships between pulmonary vascular resistance index (PVRI) and Fontan failure have not been studied. The objective was to determine whether the absence of subpulmonary ventricle in the Fontan circulation would make patients more vulnerable to even low-level elevations in PVRI, and when coupled with low cardiac index, this would identify patients at increased risk of Fontan failure. Two hundred sixty-one adult Fontan patients underwent cardiac catheterization; age 26±3 years, men 146 (56%), atriopulmonary Fontan 144 (55%). Patients were divided into 2 groups: those with high PVRI (>2 WU·m2) and low cardiac index <2.5 L min-1 m-2 (group 1, n=70, 30%), and those with normal PVRI and normal cardiac index (group 2, n=182, 70%). Fontan failure was defined by the composite of all-cause mortality, listing for heart transplantation, or initiation of palliative care. There were 68 (26%) cases of Fontan failure during a mean follow-up of 8.6±2.4 years. When compared with group 2, freedom from Fontan failure was significantly lower in group 1: 66% versus 89% at 5 years. The combination of high PVRI and low cardiac index was an independent risk factor for Fontan failure (hazard ratio, 1.84; 95% confidence interval, 1.09-2.85). When coupled with low cardiac index, even mild elevations in PVRI identify patients at high risk of Fontan failure. This suggests that pulmonary vascular disease is a key mechanism underlying Fontan failure and supports further studies to understand the pathophysiology and target treatments to pulmonary vascular tone in this population.

The Use of Oral Sildenafil for Management of Right Ventricular Dysfunction After Pediatric Heart Transplantation

High pulmonary vascular resistance index (PVRI) can lead to right ventricular dysfunction and failure of the donor heart early after pediatric heart transplantation. Oral pulmonary vasodilators such as sildenafil have been shown to be effective modifiers of pulmonary vascular tone. We performed a retrospective, observational study comparing patients treated with sildenafil ("sildenafil group") to those not treated with sildenafil ("nonsildenafil group") after heart transplantation from 2007 to 2012. Pre- and posttransplant data were obtained, including hemodynamic data from right heart catheterizations. Twenty-four of 97 (25%) transplant recipients were transitioned to sildenafil from other systemic vasodilators. Pretransplant PVRI was higher in the sildenafil group (6.8 ± 3.9 indexed Woods units [WU]) as compared to the nonsildenafil group (2.5 ± 1.7 WU, p=0.002). In the sildenafil group posttransplant, there were significant decreases in systolic pulmonary artery pressure, mean pulmonary artery pressure, transpulmonary gradient and PVRI (4.7 ± 2.9 WU before sildenafil initiation to 2.7 ± 1 WU on sildenafil, p=0.0007). While intubation time, length of inotrope use and time to hospital discharge were longer in the sildenafil group, survival was similar between both groups. Oral sildenafil was associated with a significant improvement in right ventricular dysfunction and invasive hemodynamic measurements in pediatric heart transplant recipients with high PVRI early after transplant.

Four- and Seven-Year Outcomes of Patients With Congenital Heart Disease–Associated Pulmonary Arterial Hypertension (from the REVEAL Registry)

Uncorrected congenital heart disease (CHD) frequently leads to pulmonary arterial hypertension (PAH), the most severe form of which is Eisenmenger syndrome (ES). We compared patients with idiopathic or heritable PAH (IPAH or HPAH; n = 1,626) against those with CHD-associated PAH (n = 353) who were enrolled in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL Registry). Of patients with CHD-associated PAH, 151 had ES. Compared with the IPAH or HPAH cohort, the ES cohort had greater systemic blood flow (2 ± 1 vs 3 ± 2 L/min/m(2), p <0.001), lower mean right atrial pressure (10 ± 6 vs 7 ± 4 mm Hg, p <0.001), higher mean pulmonary artery pressure (53 ± 14 vs 65 ± 17 mm Hg, p <0.001), higher pulmonary vascular resistance index (22 ± 12 vs 32 ± 31 Wood units × m(2), p <0.001), and lower systemic arterial oxygen saturation at rest (92 ± 11% vs 84 ± 13%, p <0.001). At 4 years from enrollment and 7 years from diagnosis, survival rate was similar between IPAH or HPAH and CHD-associated PAH cohorts. For the overall CHD-associated PAH cohort, longer 6-minute walk distance, lower mean right atrial pressure, brain natriuretic peptide level <50 pg/ml, and the presence of acute vasoreactivity were predictors of survival at 4 years from enrollment; younger age and lower mean right atrial pressure were predictors of survival at 7 years from diagnosis. In conclusion, these observations support predicted physiologic differences (e.g., hemodynamics) between patients with IPAH or HPAH and patients with CHD-associated PAH, with or without a systemic-pulmonary shunt. These differences, however, did not translate into significantly improved 4- and 7-year survival rates in patients with ES versus IPAH or HPAH and CHD-associated PAH.

Increased Transpulmonary Gradient Predicts Functional Class, Mortality, and RV Dysfunction by MRI in Patients with Sickle Cell Associated Pulmonary Hypertension

AbstractAbstract 89▪▪This icon denotes a clinically relevant abstract Background:Patients with sickle cell disease (SCD) and pulmonary hypertension (PH) have increased mortality. Whether SCD-associated PH (SCD-PH) is predominantly a pulmonary pre-capillary (PAH) vs. post-capillary (PVH) process is an area of ongoing investigation. SCD-PH is often complicated by high cardiac output (CO) related to anemia.The transpulmonary gradient (TPG) represents a pressure differential across the pulmonary vascular bed that the right ventricle (RV) has to overcome regardless of the total volume being ejected and has been employed to determine eligibility for cardiac transplantation because it eliminates the confounding effect of CO (PVR=TPG/CO). Typically, a TPG ≥ 12 mmHg indicates significant PAH with increased risk of acute RV failure post-transplantation.With significant PAH, there is often morphologic adaptation by the RV. MRI enables accurate quantification of RV function and structure. In idiopathic PAH, RV dilation and decreased function have been correlated with poor prognosis. Thus, we hypothesize that patients with SCD and a TPG ≥ 12 mmHg would have lower functional capacity, increased mortality, and MRI evidence of RV dysfunction. Materials & Methods:Five hundred and thirty one consecutive patients (age 35.6 ± 12.6, 54% (n=284) female, 73% (n=387) HbSS phenotype) with SCD were prospectively screened for PH using echocardiography (tricuspid regurgitant jet ≥ 2.5 m/s) without any exclusion criteria. Eighty four patients (age 41 ± 13, 55% (n=46) female, 82% (n=69) HbSS phenotype, mean Hb 8.8 ± 1.7) underwent RHC, and forty-one patients (age 42 ± 15, 54% (n=22) female, 80% (n=33) HbSS phenotype, mean Hb 8.9 ± 1.8) underwent cardiac MRI (CMR) within one week of RHC. CMR sequences consisted of cine imaging and late gadolinium enhancement imaging. Results:Of the 84 catheterized patients, forty-six had a TPG ≥ 12 mmHg and 38 had a TPG < 12 mmHg. Of the 41 patients who had both RHC and CMR, twenty-one had a TPG ≥ 12 mmHg and 20 had a TPG < 12 mmHg. Those with a TPG ≥ 12 mmHg had higher mortality (median years from enrollment to death were 4.0 vs. 4.7 years with 21 (46%) deaths in the high TPG group vs. 6 (16%) deaths in the lower TPG group, p=0.008), poorer functional class (p=0.007), shorter 6-minute walk distance (p=0.003), higher pulmonary vascular resistance index (p<0.001), and lower cardiac index (p=0.001). High TPG patients demonstrated significantly more abnormal CMR markers of RV dysfunction, including lower tricuspid annular plane excursion (p=0.001) and RV ejection fraction (p=0.002). High TPG patients also showed a non-significant trend for other markers of RV dysfunction, including higher RV end-diastolic volume index (EDVI) and RV mass index (MI), and lower RV stroke volume index (SVI). Recently validated CMR markers of pulmonary hypertension including septal-to-LV-free-wall curvature ratio (p=0.013), septomarginal trabeculae mass index (p=0.002), and ventricular mass index ratio (p=0.016) were significantly different in the high TPG group. CMR eccentricity index (EI) at end-systole (ES) was significantly greater in the high TPG group (p=0.026) without a significant change between ES and ED (end-diastole), which is consistent with the finding that there is a greater degree of RV pressure overload. In the low TPG group, the EIED was greater than EIES(p=0.001), which supports anemia-related RV volume overload rather than pressure overload. Although the left ventricular (LV) ejection fraction was similar in both groups, parameters indicative of LV dilation such as LV ESVI (p=NS) and EDVI (p=0.006) were more elevated in the low TPG group. Late gadolinium enhancement (LGE) at the RV insertion points indicative of myocardial fibrosis also occurred more frequently in the higher TPG group (p=0.030). Conclusions:A TPG ≥ 12 mmHg effectively identified patients with a lower functional capacity, MRI evidence of RV dysfunction, and overall worse prognosis. The MRI pattern of RV dysfunction in the TPG ≥ 12 mmHg is consistent with RV pressure overload. The TPG, being less subject to the confounding effects of CO, further demonstrates the functional severity of pulmonary arterial disease in SCD using objective thresholds established in the cardiac transplant literature. Disclosures:Off Label Use: Gadolinium contrast is used for late gadolinium enhancement imaging. Arai:Siemens: Dr. Arai is a principal investigator on a US Government Cooperative Research and Development Agreement (CRADA). Other.

Survival in Childhood Pulmonary Arterial Hypertension

Background— Pulmonary arterial hypertension (PAH) is a rare but important cause of morbidity and mortality in children. Methods and Results— We analyzed data from 216 patients ≤18 years of age at diagnosis who were enrolled in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). Median age at diagnosis and enrollment was 7 and 15 years, respectively. The most frequent presenting symptom was dyspnea (idiopathic/familial PAH, 53%; PAH associated with congenital heart disease, 30%). Presyncope/syncope was more frequent in patients with idiopathic PAH/familial PAH (36%) than in those with PAH associated with congenital heart disease (4%). At diagnosis, mean pulmonary artery pressure and pulmonary vascular resistance index were 56 mm Hg and 17 Wood units · m 2 , respectively. Five-year survival from diagnosis for the overall cohort was 74±6%, with no significant difference between the idiopathic PAH/familial PAH (n=122, 75±7%) and PAH associated with congenital heart disease (n=77, 71±13%) cohorts ( P =0.53). Older age at diagnosis was the only variable significantly associated with decreased survival from diagnosis. Variables at enrollment that were significantly associated with decreased survival from enrollment included higher pulmonary vascular resistance index, lower-weight z scores, and familial PAH. Additional variables at enrollment, identified in a secondary analysis, that were marginally associated with increased survival from enrollment included acute vasoreactivity (adaptation of conventional pediatric definition; P =0.087) and lower brain natriuretic peptide ( P =0.060). None of the 22 patients who were acute responders treated with high-dose calcium channel blockade as monotherapy or combination therapy died within 5 years of diagnosis. Conclusion— Using REVEAL, we identified key predictors of survival in childhood PAH. Refining these prognostic parameters should help clinicians improve outcomes. Clinical Trial Registration— URL: www.clinicaltrials.gov . Unique identifier: NCT00370214.

Decline in arterial partial pressure of oxygen after exercise: a surrogate marker of pulmonary vascular obstructive disease in patients with atrial septal defect and severe pulmonary hypertension

To examine the utility of decline in arterial partial pressure of oxygen after exercise as a marker of pulmonary vascular obstructive disease in patients with atrial septal defect and pulmonary hypertension. Treadmill exercise was performed in 18 patients with atrial septal defect and pulmonary hypertension. Arterial blood gas samples were obtained before and after peak exercise. A decline in the arterial pressure of oxygen of more than 10 millimetres of mercury after exercise was considered significant based on preliminary tests conducted on the controls. Cardiac catheterisation was performed in all patients and haemodynamic data sets were obtained on room air, oxygen, and a mixture of oxygen and nitric oxide (30-40 parts per million). There were 10 patients who had more than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise and who had a basal pulmonary vascular resistance index of more than 7 Wood units per square metre. Out of eight patients who had less than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise, seven had a basal pulmonary vascular resistance index of less than 7 Wood units per square metre, p equals 0.0001. A decline in arterial partial pressure of oxygen of more than 10 millimetres of mercury predicted a basal pulmonary vascular resistance index of more than 7 Wood units per square metre with a specificity of 100% and a sensitivity of 90%. A decline in arterial partial pressure of oxygen following exercise appears to predict a high pulmonary vascular resistance index in patients with atrial septal defect and pulmonary hypertension. This test is a useful non-invasive marker of pulmonary vascular obstructive disease in this subset.

Heart transplantation in children with markedly elevated pulmonary vascular resistance: Impact of right ventricular failure on outcome

Pulmonary hypertension causes increased morbidity and mortality in adults after heart transplantation. The effect of markedly elevated pulmonary vascular resistance (PVR) on post-transplant outcomes in children has not been well described. Outcomes were compared in a retrospective study between 58 children with an elevated PVR index (PVRI) ≥ 6 U/m(2) and 205 children with a PVRI < 6 U/m(2). Patients who did and did not respond to acute vasodilator testing and patients who underwent transplant before (pre-1995) and after (post-1995) the availability of inhaled nitric oxide (iNO) were compared. The pre-transplant diagnoses, and cardiopulmonary bypass and donor ischemic times were similar between the high and low PVRI groups. High PVRI patients were older at transplant (12 ± 6.2 vs 8 ± 7.1 years, p = 0.002). The post-transplant inotrope score was higher in the high PVRI group (12 ± 12 vs 2 ± 2, p = 0.0001) and 1-year survival was worse (76% vs 81%, p = 0.03). The PVRI fell to < 6 U/m(2) with acute vasodilator testing in 21 of 49 (42%) high PVRI patients. RV failure occurred in 4 (19%) of the responders and in 14 (50%) of the non-responders (p = 0.037). One responder (5%) and 4 non-responders (14%) died of RV failure. In the period after 1995, the year iNO became clinically available, the select group of high PVRI patients who received iNO preemptively had a lower incidence of post-transplant RV failure than the group that did not receive preemptive iNO (13% vs 54%, p = 0.04). Pre-transplant vasodilator testing identified patients at higher risk for RV failure. Patients who did not respond to vasodilator testing had an increased incidence of RV failure and death from RV failure. Preemptive use of iNO was associated with a decreased incidence of RV failure.

Perioperative Considerations in HIV-Infected Liver Transplanted Patients

The introduction of highly active antiretroviral therapy (HAART) has improved survival in HIV patients, allowing them to undergo liver transplantation (OLT) in cases of end-stage liver disease. HIV patients show a higher incidence of pulmonary hypertension. The aim of this study was to evaluate pulmonary and systemic hemodynamic changes in HIV-infected patients compared with a non–HIV-infected group of patients undergoing OLT. Methods We analyzed 20 HIV-infected patients and 20 non–HIV-infected patients who underwent OLT. We analyzed preoperative cardiovascular status, as well as intra- and postoperative hemodynamic data. Hemodynamic data were recorded at 4 predefined phases during OLT and at 24, 48, and 72 hours after intensive care unit (ICU) admission. We also evaluated the following perioperative aspects: transfusion requirements, postoperative mechanical ventilation time, ventilation time, and length of ICU and of hospital stay. Results HIV-positive patients were younger than controls with a greater incidence of coinfection with hepatotropic viruses. One HIV-infected patient died in the ICU. Hemodynamic data showed a higher cardiac index and higher pulmonary vascular resistance index among HIV-infected patients, but without any clinical impact. No significant difference in blood unit transfusions, postoperative time on mechanical ventilation, or length of ICU or hospital stay was observed between the groups. Conclusions Although the number of patients studied is limited, we concluded that HIV-infected patients undergoing OLT showed similar perioperative courses as non–HIV-infected patients.