Elevated Transpulmonary Gradient Research Articles

Detrimental effects of elevated transpulmonary gradient on outcomes following restrictive mitral annuloplasty in patients with pre-existing pulmonary hypertension.

BackgroundThis study retrospectively examined the association between elevated trans-pulmonary gradient (TPG), which reflects pre-capillary contribution to pulmonary hypertension (PH), and postoperative pulmonary hemodynamics and outcomes following restrictive mitral annuloplasty (RMA) in patients with pre-existing PH.MethodsPre- and postoperative (1 month) cardiac catheterization was performed in 64 patients with severely impaired left ventricular function (i.e., ejection fraction ≤40%) and pre-existing PH (mean pulmonary artery pressure (PAP) ≥25 mmHg) who underwent RMA. Patients were segregated into two groups: low TPG (≤12 mmHg) and elevated TPG (>12 mmHg). The mean follow-up period was 54±27 months. The primary outcome seen was a change in pulmonary hemodynamics after RMA; secondary outcomes were composite adverse events, including all-cause mortality and readmission for heart failure.ResultsCompared to the low TPG group, patients in the elevated TPG group were more likely to show a postoperative mean PAP of ≥25 mmHg (84% vs. 38%), TPG of >12 mmHg (79% vs. 11%), and pulmonary vascular resistance of ≥240 dynes/sec/cm−5 (84% vs. 6.7%) (all P<0.001), although both groups showed comparable degrees of mitral regurgitation improvement. Serial echocardiography demonstrated that Doppler-derived systolic PAP, which once decreased in both groups, remained stable in the low group while steadily increasing in the elevated group (group effect P<0.001). Patients with elevated TPG had lower freedom from composite adverse events (5-year, 20% vs. 70%, P=0.003). After adjusting for baseline covariates, the elevated TPG was independently associated with increased risk of adverse events (adjusted hazard ratio 2.9, 95% CI: 1.2–6.9, P=0.017).ConclusionsElevated TPG negatively affects postoperative pulmonary hemodynamics and late outcomes in patients with advanced cardiomyopathy and pre-existing PH who have undergone RMA. These findings suggest that the assessment of TPG should be included in post-RMA risk stratification.

Utility of Total Cardiac and Right Ventricular Mass Ratios in Recipients with Pulmonary Hypertension: A UNOS Database Analysis

<h3>Purpose</h3> Cardiac mass ratio (CMR) is validated for donor-recipient sizing, and as a predictor of transplant outcomes. However, there is a lack of data reviewing the role CMR plays in transplant recipients with pulmonary hypertension (pHTN). In particular, the right ventricular (RV) mass ratio (RVMR) is a component of CMR not yet studied separately for this purpose. We aimed to review the relationship of CMR and RVMR with pHTN in terms of development of primary graft dysfunction (PGD) and overall survival. <h3>Methods</h3> The United Network for Organ Sharing (UNOS) database was queried for primary heart transplant patients from 1987 to 2020. Missing data was imputed using a Bayesian network. Left ventricular (LV), RV, total cardiac mass (CM), and their ratios were calculated for donors and recipients. Relevant hemodynamic variables were included in logistic regression and cox proportional-hazards models to evaluate a relationship to PGD and overall survival. A stepwise regression created parsimonious models. Covariates with statistically significant relationships to the outcomes were included in tensor product spline models. <h3>Results</h3> 62,169 patients were identified. A parsimonious logistic model for odds of PGD included RVMR (OR 0.99, p<0.001) and mean PAP (mPAP) (OR 1.00, p<0.001). A parsimonious cox model for survival included diastolic PAP (HR 1.01, p<0.001), systolic PAP (HR 1.01, p<0.001), mPAP (HR 0.98, p<0.001), transpulmonary gradient (TPG) (HR 1.01, p<0.001), and CMR (HR 0.76, p<0.001). A tensor product spline model evaluating PGD demonstrated increasing odds of PGD in patients with elevated mPAP and smaller RVMR (Figure, p<0.001). Comparable models evaluating overall survival demonstrated smaller CMR was associated with reduced survival at elevated mPAP (p<0.001) and TPG (p<0.001). <h3>Conclusion</h3> In patients with pHTN, RVMR is significantly associated with odds of developing PGD, and CMR is with overall survival. Some RV oversizing may be beneficial to mitigate the risk of PGD.

What is High Risk? Hemodynamic Definitions of Pulmonary Hypertension and Heart Transplantation Outcomes: A Contemporary Cohort Analysis

<h3>Purpose</h3> Severe pulmonary hypertension (PH) is a risk factor for heart transplantation (HT), currently defined using pulmonary vascular resistance (PVR) or transpulmonary gradient (TPG). In contrast to TPG, which is directly measured, PVR is flow-dependent measurement (PVR = TPG/cardiac output) and is subject to the shortcoming of different methods for cardiac output estimation. Recently, diastolic pulmonary gradient (DPG), defined as pulmonary artery diastolic pressure - pulmonary capillary wedge pressure (PADP-PCWP), has been proposed as a better surrogate of pulmonary vascular remodeling, but there is a lack of consensus over which of these parameters is better for predicting HT outcomes. We thus aimed to compare their relationship to HT outcomes. <h3>Methods</h3> A contemporary cohort of 157 HT recipients was reviewed for pre-HT invasive hemodynamics. Patients were dichotomized according to DPG ≥7 mmHg, PVR ≥3 Wood units, or TPG ≥12 mmHg (in accordance with a recent classification system for PH). The associations between these parameters and mortality were assessed with univariable followed by multivariable Cox regression analyses. <h3>Results</h3> Higher 5-year cardiovascular mortality was found for patients with high DPG in unadjusted survival analysis (35% vs 12%, p=0.029, Figure A) and after adjustment in multivariable analysis - HR=3.22, p=0.04. For patients < 60 years, high DPG was associated with an increased risk of 30-day mortality (OR=6.39, P=0.03), 1-year mortality (HR=3.81, P=0.02), and 5-year mortality (HR=3.28, P=0.02). Elevated PVR or TPG were not associated with mortality risk (Table), and no interaction with age was found. <h3>Conclusion</h3> For patients with PH undergoing HT, high DPG, rather than high PVR or TPG, was associated with increased short- and long-term mortality.

Haemodynamic Response of Pulmonary Hypertension Secondary to Left Heart Disease with Continuous Flow Left Ventricular Assist Device Therapy (CF-LVADS): Post-Transplant Outcomes

LVAD implantation is often utilised as a bridge to transplantation or candidacy in those with pulmonary hypertension secondary to left heart disease (PHLHD). Pulmonary hypertension portends poorer outcomes post-transplant. We compared pre and post implantation haemodynamic response and outcomes in patients who normalise transpulmonary gradient (TPG) to those who do not. Retrospective review of CF-LVAD patients was conducted for right heart catheter derived haemodynamic measurements and post-transplant outcomes from a single instituition. 219 CF-LVADs were implanted between October 2004 and September 2019. 48 patients had TPG greater than 12 prior to implantation. 1 patient was excluded for incomplete data. 28 patients normalised TPG (Gp 1) and 17 patients had elevated TPG (Gp 2) at first follow up. Table 1 describes the haemodynamic assessment of the two groups. At baseline, Gp 1 patient had significantly lower PVR, p=0.04. At follow-up, Gp 1 patients had significantly lower RAP, p<0.0001 and PP, =0.003. Gp 1 patients were more likely to survive on pump, p=0.03, more likely to be transplanted, p=0.03 and survived longer post transplant, p=0.04. Baseline pulmonary vascular resistance may provide prognostic information in CF-LVAD patients with PHLHD. Early normalization in TPG is associated with favourable haemodynamic response.

Incremental Value of ePLAR-The Echocardiographic Pulmonary to Left Atrial Ratio in the Assessment of Sub-Massive Pulmonary Emboli.

Background: Acute pulmonary embolism (PE) is characterized hemodynamically by abrupt obstruction in trans-pulmonary blood flow. The echocardiographic Pulmonary to Left Atrial ratio (ePLAR, tricuspid regurgitation Vmax/mitral E/e’) has been validated as a non-invasive surrogate for trans-pulmonary gradient (TPG) that accurately differentiates pre-capillary from post-capillary chronic pulmonary hypertension. This study assessed ePLAR as an incremental echocardiographic assessment tool compared with traditional measures of right ventricular pressure and function. Methods: In total, 110 (57.4 ± 17.6 years) patients with confirmed sub-massive pulmonary emboli with contemporaneous echocardiograms (0.3 ± 0.9 days) were compared with 110 age-matched controls (AMC). Results: Tricuspid velocities were higher than AMC (2.6 ± 0.6 m/s vs. 2.4 ± 0.3 m/s, p < 0.05), although still consistent with “normal” right ventricular systolic pressures (34.2 ± 13.5 mmHg vs. 25 ± 5.3 mmHg, p < 0.05) with lower mitral E/e’ values (8.2 ± 3.8 vs. 10.8 ± 5.1, p < 0.05). ePLAR values were higher than AMC (0.36 ± 0.14 m/s vs. 0.26 ± 0.10, p < 0.05) suggesting significantly elevated TPG. Detection of abnormal echocardiographic findings increased from 29% (TRVmax ≥ 2.9 m/s) and 32% (reduced tricuspid annular plane systolic excursion) to 70% with ePLAR ≥ 0.3 m/s. Conclusions: Raised ePLAR values in acute sub-massive pulmonary embolism suggest elevated trans-pulmonary gradients even in the absence of acutely increased pulmonary artery pressures. ePLAR dramatically increases the sensitivity of echocardiography for detection of hemodynamic perturbations in sub-massive pulmonary embolism patients, which may offer clinical utility in diagnosis and management.

(429) - Elevated Transpulmonary Gradient Is a Predictor of Survival in Patients with WHO Group II Pulmonary Hypertension Treated with Continuous-Flow Left Ventricular Assist Devices (CF-LVAD)

poorly understood. Methods: Data from ASCEND-HF, a randomized clinical trial of patients with acute heart failure (AHF) regardless of left ventricular ejection fraction (LVEF), was used to characterize LFTs at baseline. Logistic regression assessed the association of LFTs and 30-day all-cause mortality and HF rehospitalization; Cox proportional hazards models were used for 180-day all-cause mortality among patients alive at a day 30 landmark. Regression was performed using continuous variables (transformed for linearity assumptions when appropriate) and a dichotomous variable (normal vs. abnormal) for each liver function test. Separate analyses were performed for individual LFT. Abnormal bilirubin was defined as O1.0 mg/dL; for AST and ALT, abnormal values were defined as O35 U/L. Results: Among 4,228 ASCEND-HF patients with LFT data, 42% had abnormal total bilirubin, 22% had abnormal ALT, and 30% had abnormal AST on admission. Patients with abnormal LFTs were younger, had lower body mass index, and lower LVEF compared to those with admission LFTs within the normal range. In multivariable models, higher levels of total bilirubin levels were associated with increased 30-day mortality or HF rehospitalization (HR 1.17 per unit change, 95% CI 1.04, 1.32), and a non-significant trend for 180-day mortality (HR 1.10, 95% CI 0.97, 1.25) (Table 1). Compared with normal baseline LFTs, the presence of an abnormal bilirubin was independently associated with increased 30-day all-cause mortality or HF rehospitalization (HR 1.24, 95% CI 1.00, 1.54) and 180-day mortality (HR 1.32, 95% CI 1.08, 1.62). After adjustment, there was no association between AST or ALT and either outcome. Conclusions: In this trial of patients with AHF, abnormalities in LFTs were common on presentation. Elevated total bilirubin, but no other liver function test, was independently associated with worse outcomes at 30and 180-days.

Elevated Transpulmonary Gradient is a Predictor of Survival in Patients with WHO Group II Pulmonary Hypertension Treated with Continuous-flow Left Ventricular Assist Devices (CF-LVAD)

Elevated Transpulmonary Gradient is a Predictor of Survival in Patients with WHO Group II Pulmonary Hypertension Treated with Continuous-flow Left Ventricular Assist Devices (CF-LVAD)

Use of pulmonary arterial hypertension-approved therapy in the treatment of non-group 1 pulmonary hypertension at US referral centers.

Pulmonary hypertension (PH) is a frequent complication of left heart disease and parenchymal lung disease, and it portends increased mortality. A growing number of medications are approved for the treatment of World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH). However, they are not well studied in PH of other etiologies (WHO groups 2-5). We sought to assess treatment approaches used by PAH referral centers in this diverse group of patients. We developed a semiquantitative online survey designed to evaluate the use of PAH-approved therapy by pulmonary vascular disease centers in the United States for management of non-group 1 PH. Thirty of 50 centers completed the survey. Almost all centers (93%) reported using PAH therapy for patients with non-group 1 PH, including 77% with group 2 PH and 80% with group 3 PH. Elevated transpulmonary gradient or pulmonary vascular resistance and the presence of right ventricular (RV) dysfunction were commonly cited as supporting use of PAH therapy in patients with PH secondary to left heart disease. For patients with PH and concomitant parenchymal lung disease, degree of pulmonary function impairment and RV dysfunction were most important in influencing use of PAH therapy. In conclusion, pulmonary vascular disease treatment centers use PAH-approved therapy for patients with WHO group 2-5 PH, mostly relying on hemodynamics and assessment of RV function to identify candidates for therapy. Clinical trials designed to test the efficacy of PAH therapy in PH due to left heart and lung disease are needed, as clinical practice has extended beyond the evidence for these etiologies of PH.

ECHOCARDIOGRAPHIC PULMONARY/LEFT ATRIAL RATIO: A NOVEL AND ROBUST NON-INVASIVE DISCRIMINATOR OF PRE-CAPILLARY VERSUS POST-CAPILLARY PULMONARY HYPERTENSION

Right heart catheterisation (RHC) is the gold-standard for differentiating pre-capillary (high trans-pulmonary gradient (TPG), normal wedge pressure) pulmonary hypertension (PHT) from post-capillary (elevated wedge pressure, with or without elevated TPG). This new non-invasive parameter ePLAR is

Pulmonary artery diastolic pressure gradient as an indicator of severity of illness in patients with pulmonary hypertension related to left-sided heart disease

Pulmonary hypertension (PH) due to left-sided heart disease (Group 2 PH) is most commonly due to passive backward transmission of elevated left-sided heart pressures. A subgroup of these patients develop pulmonary artery remodeling, resulting in systolic and mean pulmonary artery pressures that are 'reactive' or 'out of proportion' to the elevated left-sided heart pressures. These patients have historically been identified by a transpulmonary gradient (TPG) > 12 mmHg. However, since diastolic pulmonary artery pressures are less susceptible to changes in pulmonary blood flow, a diastolic pulmonary gradient (DPG) ⩾ 7 mmHg may be a superior indicator of worse clinical function and prognosis. Based on measurements from a right-heart catheterization (RHC) database (Baylor College of Medicine, Houston, TX, USA), comparisons of several clinical parameters were made among three Group 2 PH patients: normal TPG and DPG (Group 2A), elevated TPG and normal DPG (Group 2B), and elevated TPG and DPG (Group 2C). Among 173 RHCs, 39 were found to have Group 2 PH. Among these 39 cases, 10 (32%), 13 (32%), and 16 (36%) cases were categorized into Groups 2A, 2B, and 2C, respectively. Group 2C patients had significantly worse 6-min walk distance (308 ± 69 m) than Group 2A (425 ± 81 m) and Group 2B (350 ± 103 m) (p = 0.038). There was no significant difference in cardiac output, cardiac index, and right atrial pressure among the three subgroups. Among patients with Group 2 PH, elevated DPG proved to be a more specific indicator of worse functional status than the historically used TPG. International guidelines and protocols for performing RHC for the assessment and diagnosis of PH should include the measurement of DPG.

EPLAR: the echocardiographic pulmonary to left atrial ratio - conceptualising a new parameter for the assessment of pulmonary hypertension. Foundation data from 16,356 normal echocardiograms

Background: ePLAR = TRVmax/E:E’ (maximum tricuspid regurgitation continuous wave Doppler velocity divided by the transmitral E wave: mitral annular DTI E’ wave ratio) is proposed for differentiating pre-capillary pulmonary hypertension (Pre-cap PHT high trans-pulmonary gradient, normal pulmonary wedge pressure) from post-capillary physiology (Post-cap elevatedwedge pressure, +/elevated trans-pulmonary gradient) secondary to left heart disease. Methods: Patients with right ventricular systolic pressure >35mmHg were classified by right heart catheterisation as pre-cap, post-cap PHT or not pulmonary hypertensive (mean pulmonary arterypressure 0.23 had high discriminatory power by ROC analysis (AUC = 0.832). The ePLAR for 1000 population normal echocardiograms (mean age 56±16yrs) was 0.30±0.09. Conclusions: ePLAR is a simple echocardiographic parameter which can accurately differentiate pre-capillary pulmonary hypertension from the more common postcapillary aetiology. The use of ePLAR has the potential to streamline screening of patients for specific pulmonary vasodilator therapy.

The Diastolic Pulmonary Gradient Does Not Predict Survival in Patients With Pulmonary Hypertension Due to Left Heart Disease

ObjectivesThis study sought to evaluate if diastolic pulmonary gradient (DPG) can predict survival in patients with pulmonary hypertension due to left heart disease (PH-LHD). BackgroundPatients with combined post- and pre-capillary PH-LHD have worse prognosis than those with passive pulmonary hypertension. The transpulmonary gradient (TPG) and pulmonary vascular resistance (PVR) have commonly been used to identify high-risk patients. However, these parameters have significant shortcomings and do not always correlate with pulmonary vasculature remodeling. Recently, it has been suggested that DPG may be better a marker, yet its prognostic ability in patients with cardiomyopathy has not been fully assessed. MethodsA retrospective cohort of 1,236 patients evaluated for unexplained cardiomyopathy at Johns Hopkins Hospital was studied. All patients underwent right heart catheterization and were followed until death, cardiac transplantation, or the end of the study period (mean time 4.4 years). The relationships between DPG, TPG, or PVR and survival in subjects with PH-LHD (n = 469) were evaluated with Cox proportional hazards regression and Kaplan-Meier analyses. ResultsDPG was not significantly associated with mortality (hazard ratio [HR]: 1.02, p = 0.10) in PH-LHD whereas elevated TPG and PVR predicted death (HR: 1.02, p = 0.046; and HR: 1.11, p = 0.002, respectively). Similarly, DPG did not differentiate survivors from non-survivors at any selected cut points including a DPG of 7 mm Hg. ConclusionsIn this retrospective study of patients with cardiomyopathy and PH-LHD, an elevated DPG was not associated with worse survival.

The Importance of Assessing Arteriovenous Fistula Patency in the Setting of Persistent Pulmonary Hypertension After Combined Liver Kidney Transplant

Introduction: Portopulmonary hypertension (PoPH) is a well-documented vascular complication in patients with end-stage liver disease. In the setting of left ventricular dysfunction, patients with cirrhosis and ESRD can develop pulmonary venous hypertension. The hemodynamic effects of arteriovenous fistulas (AVFs) in patients with both cirrhosis and ESRD in exacerbating pulmonary arterial and venous hypertension are rarely reported in the literature. A 54-year-old male with a history of 2 renal transplants and a liver transplant for cirrhosis presented with several weeks of progressive dyspnea, orthopnea, and lower extremity edema. His first renal allograft failed due to chronic rejection, requiring him to resume hemodialysis in 2002 through a left upper extremity AVF. He began having recurrent ascites in 2008 and was referred for evaluation of possible liver kidney transplant. His echocardiogram showed an elevated right ventricular systolic pressure of 74.8 mmHg. Subsequent right heart catheterization (RHC) was consistent with pulmonary arterial hypertension, with mean pulmonary arterial pressure (mPAP) 41 mmHg, pulmonary vascular resistance (PVR) 254 dyne*sec/cm5, and cardiac index (CI) 4 dyne*sec/cm5. After 6 months of therapy with sildenafil, his mPAP decreased to 28 mmHg, allowing him to successfully undergo a simultaneous liver kidney transplant in 2009. The patient did well until 3 years later, when he presented with volume overload. Repeat echocardiogram revealed a preserved ejection fraction and a mPAP of 81.6 mmHg. The patent’s RHC revealed a relatively normal PCWP and elevated transpulmonary gradient (TPG) concerning for worsening pulmonary hypertension (mPAP 55 mmHg, PVR 343 dyne*sec/cm5). His symptoms progressed despite receiving aggressive diuresis and ICU support for right ventricular syndrome. Based on the patient’s high cardiac output and pulmonary hypertension with normal PVR, the diagnosis of high output heart failure was made. The patient’s AVF was ligated out of clinical concern for high output through the patient’s fistula causing exacerbation of pulmonary arterial and venous hypertension. Repeat RHC showed decrease in mPAP to 36.6 mmHg 7 months after AVF ligation, consistent with continued improvement of respiratory symptoms with stable liver and kidney allograft function. This case illustrates the potential importance of evaluating graft patency in patients with pre-existing PoPH, given the risk of developing high output heart failure. Given the probability that an AVF will remain patient after renal transplant, clinicians should carefully consider assessing AVF patency and flow in the setting of worsening clinical signs and symptoms suggestive of high-output heart failure.

Pulmonary vascular dysfunction in ARDS.

Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (PH). Multiple factors may contribute to the development of PH in this setting. In this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ARDS and reported on mortality in the period 1977 to 2010. There were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. In order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. We consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ARDS, including the important effects of mechanical ventilation. Pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. The great variability in management strategies within and between studies means that no unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir Crit Care Med 182:1123–1128, 2010) have recently reported that elevated pulmonary vascular resistance (PVR) and TPG were independently associated with increased mortality in ARDS, in a large trial with protocol-defined management strategies and using lung-protective ventilation. We then considered the existing literature to determine whether the relationship between PVR/TPG and outcome might be causal. Although we could identify potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. Nonetheless, abnormally elevated PVR/TPG may provide a useful index of disease severity and progression. Further studies are required to understand the role and importance of pulmonary vascular dysfunction in ARDS in the era of lung-protective ventilation.

Clinical characterization and survival of patients with borderline elevation in pulmonary artery pressure.

Normal resting mean pulmonary artery pressure (PAP) is 8-20 mmHg. Pulmonary hypertension is defined as mean PAP of ≥25 mmHg. Borderline PAP levels of 21-24 mmHg are of unclear significance. We sought to determine the clinical characteristics and survival of subjects with mean PAP of 21-24 mmHg. We examined 1,491 patients enrolled in the Cleveland Clinic Pulmonary Hypertension Registry between February 1990 and May 2012 with baseline right heart catheterization. The relationship between PAP and all-cause mortality was assessed by Cox models and a tree-based analysis. Sixty-three patients had borderline PAP (underlying conditions: 12 left heart disease, 20 respiratory disease, 17 connective-tissue disease, 4 others, and 10 none). We then compared 3 groups: borderline PAP without heart or lung disease ([Formula: see text]), normal PAP without heart or lung disease ([Formula: see text]), and category 1 pulmonary arterial hypertension (PAH; [Formula: see text]). Borderline-PAP patients had levels of hemodynamic and functional compromise between those for normal-PAP patients and those for patients with PAH. Borderline PAP was associated with increased mortality compared to normal PAP (hazard ratio: 4.03 [95% confidence interval: 0.78-20.80], [Formula: see text]). A tree-based analysis demonstrated almost identical cut points in mean PAP (≤20, 21-26, and ≥27 mmHg) associated with differential survival ([Formula: see text]). Connective-tissue disease and an elevated transpulmonary gradient were predictors of worse survival in the borderline-PAP population. Borderline PAP elevation is associated with decreased survival, particularly in the context of connective-tissue disease and an elevated transpulmonary gradient.

Prognostic value of the pre-transplant diastolic pulmonary artery pressure–to–pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension

Although the transpulmonary gradient (TPG) and pulmonary vascular resistance (PVR) are commonly used to differentiate heart failure patients with pulmonary vascular disease from those with passive pulmonary hypertension (PH), elevations in TPG and PVR may not always reflect pre-capillary PH. Recently, it has been suggested an elevated diastolic pulmonary artery pressure-to-pulmonary capillary wedge pressure gradient (DPG) may be a better indicator of pulmonary vascular remodeling, and therefore, may be of added prognostic value in patients with PH being considered for cardiac transplantation. Using the United Network for Organ Sharing (UNOS) database, we retrospectively reviewed all primary adult (age > 17 years) orthotropic heart transplant recipients between 1998 and 2011. All patients with available pre-transplant hemodynamic data and PH (mean pulmonary artery pressure ≥ 25 mm Hg) were included (n = 16,811). We assessed the prognostic value of DPG on post-transplant survival in patients with PH and an elevated TPG and PVR. In patients with PH and a TPG > 12 mm Hg (n = 5,827), there was no difference in survival at up to 5 years post-transplant between high DPG (defined as ≥3, ≥5, ≥7, or ≥10 mm Hg) and low DPG (<3, <5, <7, or <10 mm Hg) groups. Similarly, there was no difference in survival between high and low DPG groups in those with a PVR > 3 Wood units (n = 6,270). Defining an elevated TPG as > 15 mm Hg (n = 3,065) or an elevated PVR > 5 (n = 1,783) yielded similar results. This large analysis investigating the prognostic value of DPG found an elevated DPG had no effect on post-transplant survival in patients with PH and an elevated TPG and PVR.

Pulmonary Hypertension Associated with Left Heart Disease

Left heart disease (LHD) is probably the most frequent cause of pulmonary hypertension (PH). Although rheumatic mitral valve stenosis has been in the past the most common cause of this condition, PH-LHD mainly results from heart failure related to systolic and/or diastolic dysfunction of the left ventricle and is associated with elevated left-sided cardiac filling pressures. Most patients have passive increase in pulmonary arterial pressure because of backward transmission of the elevated left atrial pressure, whereas a small subset develop severe PH with elevated transpulmonary gradient and pulmonary vascular resistance. When present, PH is usually associated with a poor prognosis and increased mortality. Optimizing heart failure regimens and corrective valve surgery are the cornerstones of the treatment of PH in LHD. Although PH-LHD may evolve to right ventricular failure and is associated with some changes in the pulmonary vascular bed similar to pulmonary arterial hypertension (PAH), there is no evidence-based data to support the use of PAH-specific therapies in the setting of PH-LHD. However, recent studies suggest the usefulness of sildenafil, a phosphodiesterase-5 inhibitor. This review addresses the epidemiology, pathophysiology, risk factors, and treatment controversies of PH due to LHDs.

Borderline Mean Pulmonary Artery Pressure in Patients With Systemic Sclerosis: Transpulmonary Gradient Predicts Risk of Developing Pulmonary Hypertension

To determine whether patients with systemic sclerosis (SSc) and borderline mean pulmonary artery pressure (PAP) at cardiac catheterization are more likely to develop pulmonary hypertension (PH) than those in whom pulmonary pressure is normal. Patients with SSc in whom PH and significant interstitial lung disease had been excluded at baseline were enrolled in our prospective cohort. Analysis of followup data identified patients who met prespecified criteria prompting repeat catheterization to reassess for possible PH. Using Kaplan-Meier, receiver operating characteristic, and Cox regression methods, we studied the development of PH and death. Of 228 patients in this study, 86 had borderline mean PAP (21-24 mm Hg) at baseline. Following prespecified criteria, 76 patients underwent repeat catheterization, and 29 of these developed PH. Two cases were related to disease of the left side of the heart. The average mean PAP increased from baseline (20.2 mm Hg) to followup (24.3 mm Hg) (P<0.05 by Student's t-test). Patients with borderline mean PAP were more likely to develop PH than patients with mean PAP≤20 mm Hg (P<0.001 by log rank test, hazard ratio [HR] 3.7). A transpulmonary gradient (TPG)≥11 mm Hg at baseline also predicted PH (P<0.001 by log rank test, HR 7.9). Incident development of pulmonary arterial hypertension (PAH) was not benign, with a mortality of 18% within 3 years. Our findings indicate that borderline mean PAP and an elevated TPG in patients with SSc predict progression to PH. These patients should be monitored closely for the development of PH. Our findings indicate that catheterization data are useful in patients considered at risk of PAH.

RV dysfunction by MRI is associated with elevated transpulmonary gradient and poor prognosis in patients with sickle cell associated pulmonary hypertension

Background Patients with sickle cell disease (SCD) and pulmonary hypertension (PH) have increased mortality. SCD-PH is often complicated by high cardiac output (CO) related to anemia. The transpulmonary gradient (TPG) reflects a pressure differential across the pulmonary vascular bed without the confounding effect of CO (PVR=TPG/CO). Based on the cardiac transplant literature, a TPG ≥ 12 mmHg indicates significant pulmonary arterial hypertension (PAH). With PH, there is often morphologic adaptation by the right ventricle (RV). In idiopathic PAH, RV dilation and decreased function have been correlated with poor prognosis. We hypothesize that patients with SCD and a TPG ≥ 12 mmHg would have lower functional capacity, increased mortality, and evidence of RV dysfunction on cardiac MRI (CMR).

Portopulmonary hypertension: a disease in search of multi-centre cooperation

Portopulmonary hypertension: a disease in search of multi-centre cooperation