Search

Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH) worldwide, but the prevalence and risk factors for schistosomiasis-associated PAH (SchPAH) development are not well understood. Schistosomiasis-associated hepatosplenic disease (SchHSD) is thought to be a major risk factor for PAH development. Herein, we describe our plans for prospectively screening SchHSD subjects for clinical evidence of PAH at two major academic medical centers and national referral hospitals in Addis Ababa, Ethiopia and Lusaka, Zambia. The screening study will primarily be conducted by echocardiography, in addition to clinical assessments. Plasma samples will be drawn and banked for subsequent analysis based on preclinical animal model rationale. If successful, this study will demonstrate feasibility of conducting prospective cohort studies of SchPAH screening in schistosomiasis-endemic regions of Africa, and provide initial data on clinic-based disease prevalence and potential mechanistic biomarkers underlying disease pathogenesis.

Pulmonary arterial hypertension (PAH) is a disease of the lung blood vessels that results in right heart failure. PAH is thought to occur in about 5% to 10% of patients with hepatosplenic schistosomiasis, particularly due to S. mansoni. The lung blood vessel injury may result from a combination of embolization of eggs through portocaval shunts into the lungs causing localized Type 2 inflammatory response and vessel remodeling, triggering of autonomous pathology that becomes independent of the antigen, and high cardiac output as seen in portopulmonary hypertension. The condition is likely underdiagnosed as there is little systematic screening, and risk factors for developing PAH are not known. Screening is done by echocardiography, and formal diagnosis requires invasive right heart catheterization. Patients with Schistosoma-associated PAH show reduced functional capacity and can be treated with pulmonary vasodilators, which improves symptoms and may improve survival. There are animal models of this disease that might help in understanding disease pathogenesis and identify novel targets to screen and treatment. Pathogenic mechanisms include Type 2 immunity and activation and signaling in the TGF-β pathway. There are still major uncertainties regarding Schistosoma-associated PAH development, course and treatment.

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly-sponsored insurance during the COVID-19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly-sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID-19 pandemic. The relatively small impact of the COVID-19 pandemic on pulmonary hypertension-related outcomes was unexpected but may be due to pre-established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID-19 pandemic, patients who were on publiclysponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary hypertension (PH) is prevalent in those with end‐stage kidney disease (ESKD) and poses a barrier to kidney transplant due to its association with poor outcomes. Studies examining these adverse outcomes are limited and often utilize echocardiographic measurements of pulmonary artery systolic pressure (PASP) instead of the gold standard right heart catheterization (RHC). We hypothesized that in ESKD patients deemed ineligible for kidney transplant because of an echocardiographic diagnosis of PH the predominant cause of PH is hypervolemia and is potentially reversible. Methods: We conducted a prospective study of 16 patients with ESKD who were denied transplant candidacy. Prior echocardiograms and RHCs were reviewed for confirmation of PH. Patients were admitted for daily sessions of ultrafiltration for volume removal and repeat RHCs were performed following intervention. RHC parameters and body weight were compared before and after intervention. Statistical analysis was performed using PRISM GraphPad software. A p‐value <.05 was considered statistically significant. Results: Following intervention, the mean pulmonary artery pressure (mPAP) and pulmonary arterial wedge pressure decreased from 45.0 ± 3.06 to 29.1 ± 7.77 mmHg (p <.0001) and 22.2 ± 5.06 to 13.1 ± 7.25 mmHg (p =.003), respectively. The pulmonary vascular resistance decreased from 4.73 ± 1.99 to 4.28 ± 2.07 WU (p =.30). Eleven patients from the initial cohort underwent successful kidney transplantation post‐intervention with 100% survival at 1‐year. Conclusions: In ESKD patients, diagnoses of PH made by echocardiography may be largely due to hypervolemia and may be optimized using an intensive ultrafiltration strategy to restore transplant candidacy. [ABSTRACT FROM AUTHOR]

Background and Aims: Invasive hemodynamics may provide a more nuanced assessment of cardiac function and risk phenotyping in patients undergoing cardiac surgery. The systemic pulse pressure (SPP) to central venous pressure (CVP) ratio represents an integrated index of right and left ventricular function and thus may demonstrate an association with valvular heart surgery outcomes. This study hypothesized that a low SPP/CVP ratio would be associated with mortality in valvular surgery patients.Methods: This retrospective cohort study examined adult valvular surgery patients with preoperative right heart catheterization from 2007 through 2016 at a single tertiary medical center (n = 215). Associations between the SPP/CVP ratio and mortality were investigated with univariate and multivariate analyses.Results: Among 215 patients (age 69.7 ± 12.4 years; 55.8% male), 61 died (28.4%) over a median follow-up of 5.9 years. A SPP/CVP ratio <7.6 was associated with increased mortality (relative risk 1.70, 95% confidence interval [CI] 1.08-2.67, p = .019) and increased length of stay (11.56 ± 13.73 days vs. 7.93 ± 4.92 days, p = .016). It remained an independent predictor of mortality (adjusted odds ratio 3.99, 95% CI 1.47-11.45, p = .008) after adjusting for CVP, mean pulmonary artery pressure, aortic stenosis, tricuspid regurgitation, smoking status, diabetes mellitus, dialysis, and cross-clamp time.Conclusions: A low SPP/CVP ratio was associated with worse outcomes in patients undergoing valvular heart surgery. This metric has potential utility in preoperative risk stratification to guide patient selection, prognosis, and surgical outcomes. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a broad term describing the mean pulmonary artery pressure, as measured by right heart catheterization, exceeds 20mmHg. Pulmonary arterial hypertension (PAH) exists when PH is accompanied by a normal wedge pressure and elevated pulmonary vascular resistance. PAH is typified by dysmorphic and dysfunctional pulmonary arterial vasculature. Attempting to restore the functionality of the pulmonary artery is a hallmark of care to the PAH patient. Riociguat is a powerful stimulator of soluble guanylate cyclase and increases blood flow through the pulmonary arteries by dilating vascular smooth muscle cells. This review examines the pharmacology of riociguat, the fundamental clinical trials applying it to PAH patients, practical aspects when selecting its use, and future directions for its utilization. [ABSTRACT FROM AUTHOR]

Background: Pulmonary artery proportional pulse pressure (PAPP) was recently shown to have prognostic value in heart failure (HF) with reduced ejection fraction (HFrEF) and pulmonary hypertension. We tested the hypothesis that PAPP would be predictive of adverse outcomes in patients with implantable pulmonary artery pressure monitor (CardioMEMS™ HF System, St. Jude Medical [now Abbott], Atlanta, GA, USA).Methods: Survival analysis with Cox proportional hazards regression was used to evaluate all-cause deaths and HF hospitalisation (HFH) in CHAMPION trial1 patients who received treatment with the CardioMEMS device based on the PAPP.Results: Among 550 randomised patients, 274 had PAPP ≤ the median value of 0.583 while 276 had PAPP>0.583. Patients with PAPP≤0.583 (versus PAPP>0.583) had an increased risk of HFH (HR 1.40, 95% CI 1.16-1.68, p=0.0004) and experienced a significant 46% reduction in annualised risk of death with CardioMEMS treatment (HR 0.54, 95% CI 0.31-0.92) during 2-3 years of follow-up. This survival benefit was attributable to the treatment benefit in patients with HFrEF and PAPP≤0.583 (HR 0.50, 95% CI 0.28-0.90, p<0.05). Patients with PAPP>0.583 or HF with preserved EF (HFpEF) had no significant survival benefit with treatment (p>0.05).Conclusion: Lower PAPP in HFrEF patients with CardioMEMS constitutes a higher mortality risk status. More studies are needed to understand clinical applications of PAPP in implantable pulmonary artery pressure monitors. [ABSTRACT FROM AUTHOR]

Background: Pulmonary artery (PA) pulsitility index (PAPi) is a novel haemodynamic index shown to predict right ventricular failure in acute inferior myocardial infarction and post left ventricular assist device surgery. We hypothesised that PAPi calculated as [PA systolic pressure - PA diastolic pressure]/right atrial pressure (RAP) would be associated with mortality in the National Institutes of Health Registry for Primary Pulmonary Hypertension (NIH-RPPH).Methods: The impact of PAPi, the Pulmonary Hypertension Connection (PHC) risk score, right ventricular stroke work, pulmonary artery capacitance (PAC), other haemodynamic indices, and demographic characteristics was evaluated in 272 NIH-RPPH patients using multivariable Cox proportional hazards (CPH) regression and receiver operating characteristic (ROC) analysis.Results: In the 272 patients (median age 37.7+/-15.9years, 63% female), the median PAPi was 5.8 (IQR 3.7-9.2). During 5years of follow-up, 51.8% of the patients died. Survival was markedly lower (32.8% during the first 3years) in PAPi quartile 1 compared with the remaining patients (58.5% over 3years in quartiles 2-4; p<0.0001). The best multivariable CPH survival model included PAPi, the PHC-Risk score, PAC, and body mass index (BMI). In this model, the adjusted hazard ratio for death with increasing PAPi was 0.946 (95% CI 0.905-0.989). The independent ROC areas for 5-year survival based on bivariable logistic regression for PAPi, BMI, PHC Risk, and PAC were 0.63, 0.62, 0.64, and 0.65, respectively (p<0.01). The ROC area for 5-year survival for the multivariable logistic model with all four covariates was 0.77 (p<0.0001).Conclusions: Pulmonary artery pulsatility index was independently associated with survival in PAH, highlighting the utility of PAPi in combination with other key measures for risk stratification in this population. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance leading to right heart failure. Elevated right atrial (RA) pressure reflects right ventricular (RV) pressure overload and is an established risk factor for mortality in PH. We hypothesized that PH patients with an increased ratio of RA to LA volume index (RAVI/LAVI), would have increased mortality. Methods: We evaluated the association of RAVI/LAVI with mortality in 124 patients seen at a single academic center's PH clinic after adjusting for the REVEAL risk score, an established risk score in PH. LA and RA volume indices were measured in the four‐and two‐chamber views by two independent researchers. Multivariable logistic regression was used to model the independent association of RAVI/LAVI with survival. Results: Among 124 patients (mean age 62 ± 12.7 years, 68.6% female), each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.91, 95% CI: 1.20–3.04). In a multivariable logistic regression, each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.73, 95% CI: 1.003–2.998). Furthermore, RAVI/LAVI in the highest quartile (>1.42) was significantly associated with elevated right atrial pressure (RAP) to pulmonary artery wedge pressure ratio (RAP/PAWP) (0.76 ± 0.41, P = 0.02) compared with the lowest quartile (<0.77), suggesting an interaction between invasive hemodynamic data, atrial structural changes, and mortality in PH. Conclusions: Increased RAVI/LAVI in PH is associated with decreased survival and accounts for atrial structural remodeling related to invasive hemodynamics. These findings support further study of this index in predicting outcomes in PH. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the association of preoperative invasive hemodynamic parameters with mortality in valvular heart surgery. Design Retrospective cohort study. Setting Single tertiary academic medical center. Participants A total of 382 patients who underwent preoperative right and/or left heart catheterization before open aortic valve replacement (AVR), open mitral valve repair/replacement (MVR), or combined AVR and MVR, from July 2009 to December 2014. Interventions Retrospective chart review. Measurements and Main Results Common hemodynamic indices derived from direct catheterization measurements were assessed, including pulmonary artery systolic pressure (PASP), pulmonary artery pulse pressure (PPP), mean pulmonary capillary wedge pressure (mPCWP), pulmonary artery pulsatility index, diastolic pressure gradient, left ventricular work index, and right ventricular work index. Bivariable and multivariable associations of these measures with survival were determined using Cox proportional hazards regression. Kaplan–Meier survival curves were generated using the log-rank test. The median age of the cohort was 69 years (interquartile range 60-79 years), and 162 (42.4%) of the patients were female. Elevated PASP (hazard ratio [HR] 1.32 per 10 mmHg, p < 0.0001), elevated PPP (HR 1.48 per 10 mmHg, p < 0.0001), and elevated mPCWP (HR 1.95 per 10 mmHg, p < 0.0001) were all associated with decreased survival, as was decreased diastolic blood pressure (DBP) (p = 0.005). The combination of elevated PPP and decreased DBP was associated with the worst outcomes. Conclusions PASP, PPP, mPCWP, and DBP were significantly associated with mortality in valvular heart surgery patients. These hemodynamic parameters may be useful in risk stratification of this population subset. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the novel index pulmonary arterial proportional pulse pressure (PAPP) in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial.Methods and Results: Multivariable Cox proportional hazards and logistical regression were used to model 6-month death; death, transplantation, or left ventricular assist device (DTLVAD); and DTLVAD or heart failure rehospitalization (DTLVADHF) with respect to PAPP. Among 175 patients with final hemodynamic data, 15.5% and 33.9%, respectively, died in optimal PAPP (PAPP >0.50) and nonoptimal PAPP (PAPP ≤0.50) groups (P = .008), and PAPP was independently associated with death, DTLVAD, and DTLVADHF (P < .01 for all outcomes). The hypothesized logistic regression model with pulmonary capillary wedge pressure, creatinine, and nonoptimal PAPP had an area under the curve of 0.818 (P < .0001) for death. Furthermore, PAPP as a continuous variable was the most powerful predictor of DTLVADHF (hazard ratio 0.793 per 0.1 increase in PAPP [95% confidence interval 0.659-0.955], chi square 8.80; P = .01) in the Cox model, with no other clinical, laboratory, or hemodynamic parameters significant after adjustment for PAPP.Conclusions: PAPP, a novel parameter for right-sided proportional pulse pressure, is an independent and powerful predictor of adverse clinical outcomes in advanced HF. Increased PAPP promises to be a useful therapeutic target in patients with pulmonary arterial pressure assessment. [ABSTRACT FROM AUTHOR]

Background: Assessment of diffuse right ventricular (RV) fibrosis is of particular interest in pulmonary hypertension (PH) and heart failure (HF). Current cardiovascular magnetic resonance (CMR) T1 mapping techniques such as Modified Look-Locker inversion recovery (MOLLI) imaging have limited resolution, but accelerated and navigator-gated Look-Locker imaging for cardiac T1 estimation (ANGIE) is a novel CMR sequence with spatial resolution suitable for T1 mapping of the RV. We tested the hypothesis that patients with PH would have significantly more RV fibrosis detected with MRI ANGIE compared with normal volunteers and patients having HF with reduced (LV) ejection fraction (HFrEF) without co-existing PH, independent of RV dilitation and dysfunction. Methods: Patients with World Health Organization group 1 or group 4 PH, patients with HFrEF without PH, and normal volunteers were recruited to undergo contrast-enhanced CMR. RV and LV extracellular volume fractions (RV-ECV and LV-ECV) were determined using pre-contrast and post-contrast T1 mapping using ANGIE (RV and LV) and MOLLI (LV only). Results: Thirty-two participants (53.1 % female, median age 52 years, IQR 26-65 years) were enrolled, including n =1 2 with PH, n = 10 having HFrEF without co-existing PH, and n = 10 normal volunteers. ANGIE ECV imaging was of high quality, and ANGIE measurements of LV-ECV were highly correlated with those of MOLLI (r = 0.91; p < 0.001). The RV-ECV in PH patients was 27.2 % greater than the RV-ECV in normal volunteers (0.341 v. 0.268; p < 0.0001) and 18.9 % greater than the RV-ECV in HFrEF patients without PH (0.341 v. 0.287; p < 0.0001). RV-ECV was greater than LV-ECV in PH (RV-LV difference = 0.04), but RV-ECV was nearly equivalent to LV-ECV in normal volunteers (RV-LV difference = 0.002) (p < 0.0001 for RV-LV difference in PH versus normal volunteers). RV-ECV was linearly associated with both increasing RVEDVI (p = 0.049) and decreasing RVEF (p = 0.04) in a multivariable linear model, but PH was still associated with greater RV-ECV even after adjustment for RVEDVI and RVEF. Conclusions: Pre- and post-contrast ANGIE imaging provides high-resolution ECV determination for the RV. PH is independently associated with increased RV-ECV even after adjustment for RV dilatation and dysfunction, consistent with an independent effect of PH on fibrosis. ANGIE RV imaging merits further clinical evaluation in PH. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular (RV) failure. The failing RV, through interventricular uncoupling, deleteriously impacts the left ventricle and overall cardiac efficiency. We hypothesised that the ratio of the pulmonary artery pulse pressure to the systemic pulse pressure ("pulmonary-systemic pulse pressure ratio", or PS-PPR) would be associated with mortality in PAH.Methods: We conducted a retrospective analysis of 262 patients in the National Institute of Health Primary Pulmonary Hypertension Registry (NIH-PPH). We evaluated the association between the PS-PPR and mortality after adjustment for the Pulmonary Hypertension Connection (PHC) risk equation.Results: Among 262 patients (mean age 37.5±15.8years, 62.2% female), median PS-PPR was 1.04 (IQR 0.79-1.30). In the Cox proportional hazards regression model, each one unit increase in the PS-PPR was associated with more than a two-fold increase in mortality during follow-up (HR 2.06, 95% CI 1.40-3.02, p=0.0002), and this association of PS-PPR with mortality remained significant in the multivariable Cox model adjusted for the PHC risk equation, mean pulmonary artery pressure, and body mass index (BMI) (adjusted HR 1.81, 95% CI 1.13-2.88, p=0.01). Furthermore, PS-PPR in the upper quartile (>1.30) versus quartiles 1-3 was associated with a 68% increase in mortality after adjustment for these same covariates (adjusted HR 1.68, 95% CI 1.13-2.50, p=0.01).Conclusions: Pulmonary-systemic pulse pressure ratio, a marker of biventricular efficiency, is associated with survival in PAH even after adjustment for the PHC risk equation. Further studies are needed on the wider applications of PS-PPR in PAH patients. [ABSTRACT FROM AUTHOR]

Introduction: Right ventricular (RV) function is a key determinant of mortality in pulmonary arterial hypertension (PAH). Pulmonary effective arterial elastance (PAE) is a hemodynamic marker of total RV afterload, reflecting both resistive and pulsatile components. PAE has been shown to predict mortality in pulmonary hypertension (PH) secondary to left heart disease, but there is a paucity of data on PAE and clinical outcomes in PAH. Hypothesis: We hypothesized that PAE would be independently associated with 5-year survival in PAH, even after adjustment for the PH Connection (PHC) risk score. Methods: Using the National Institute of Health Primary PH (NIH-PPH) database, PAE was calculated by dividing the pulmonary artery systolic pressure by stroke volume. Cox proportional hazards analysis and Kaplan Meier survival curves were used to assess associations with PAE and survival during 5 years of follow-up. Results: Among 216 patients (age 38.0 ± 15.6 years; 64.8% female; 86.6% White race) with PAH, the median PAE was 2.10 (IQR 1.34-3.05). Among patients in the upper quartile (Q4) of PAE, 68.5% died during 5 years of follow-up versus 45.7% in quartiles 1-3 (Q1-Q3), (P=0.005). As shown in the Kaplan-Meier survival curves in the accompanying figure, proportional hazards were evident throughout 5 years of follow-up in Q4 versus Q1-3, and the log rank statistic was significant (P <0.0001). In a Cox proportional hazards model adjusted for the PHC risk score, PAE in Q4 was associated with a two-fold increased risk of 5-year death (HR 1.99; 95% CI 1.33-2.96; P=0.0007). PAE, as a continuous variable, was significant in a separate PHC-adjusted Cox model (HR per unit increase 1.12; 95% CI 1.04-1.21; P=0.002). Conclusions: In conclusion, PAE is independently associated with survival in PAH, even after adjustment for the PHC risk score. This underscores the importance of RV afterload on mortality in PAH. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) is a progressive condition characterized by elevated right ventricular (RV) pressure leading to deleterious interventricular interactions including left ventricular (LV) diastolic compression. There is paucity of data on the relationship of these hemodynamic/structural Interventricular interactions with clinical outcomes in PH. Hypothesis: We hypothesized that in PH, an increase in the ratio of RV end diastolic pressure (RVEDP) to pulmonary arterial wedge pressure (PAWP), RVEDP/PAWP, would be associated with corresponding structural changes in RV end diastolic dimension (RVIDd), LV end diastolic dimension (LVIDd), and that both RVEDP/PAWP and RVIDd/LVIDd ratios would be associated with increased mortality. Methods: This was a retrospective study of consecutive patients of all groups of PH in an outpatient setting at a tertiary academic center (from 2012-2017).Multivariable Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the association of RVEDP/PAWP ratio with mortality. Correlational analysis was made to assess the relationship between RVEDP/PAWP and RVIDd/LVIDd. Results: Among 116 patients (mean age 64 years +/- 13 and 68% female), each unit increase in the RVEDP/PAWP ratio was associated with over a three-fold increase in mortality (HR 3.386, 95% Cl 1.465-7.828). In the multivariable logistic regression model adjusted for the RVIDd/LVIDd, each unit increase in the RVEDP/PAWP was still significantly associated with mortality. There was a weak correlation (p<0.06) between RVEDP/PAWP and RVIDd/LVIDd suggesting a relationship between hemodynamics and ventricular structural remodeling. Patients in the lowest quartile (<0.87) of RVIDd/LVIDd had the best 4 year survival compared to the other quartiles. Conclusion: Increased RVEDP/PAWP in PH is associated with mortality and weakly correlates with ventricular structural remodeling. These findings support further study of this index for guiding risk stratification in PH patients. [ABSTRACT FROM AUTHOR]