Left Ventricular Filling Pressure in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of major pulmonary arteries with organized thrombi. Clinical risk factors for pulmonary hypertension due to left heart disease including metabolic syndrome, left-sided valvular heart disease, and ischemic heart disease are common in CTEPH patients. OBJECTIVES: The authors sought to investigate prevalence and prognostic implications of elevated left ventricular filling pressures (LVFP) in CTEPH. METHODS: A total of 593 consecutive CTEPH patients undergoing a first diagnostic right and left heart catheterization were included in this study. Mean pulmonary arterial wedge pressure (mPAWP) and left ventricular end-diastolic pressure (LVEDP) were utilized for assessment of LVFP. Two cutoffs were applied to identify patients with elevated LVFP: 1) for the primary analysis mPAWP and/or LVEDP >15 mm Hg, as recommended by the current pulmonary hypertension guidelines; and 2) for the secondary analysis mPAWP and/or LVEDP >11 mm Hg, representing the upper limit of normal. Clinical and echocardiographic features, and long-term mortality were assessed. RESULTS: LVFP was >15 mm Hg in 63 (10.6%) and >11 mm Hg in 222 patients (37.4%). Univariable logistic regression analysis identified age, systemic hypertension, diabetes, atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume as significant predictors of elevated LVFP. Atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume remained independent determinants of LVFP in adjusted analysis. At follow-up, higher LVFPs were measured in patients who had meanwhile undergone pulmonary endarterectomy (P = 0.002). LVFP >15 mm Hg (P = 0.021) and >11 mm Hg (P = 0.006) were both associated with worse long-term survival. CONCLUSIONS: Elevated LVFP is common, appears to be due to comorbid left heart disease, and predicts prognosis in CTEPH.

Larger pulmonary artery to ascending aorta ratios are associated with decreased survival of patients undergoing pulmonary endarterectomy.

Objectives: The ratio of pulmonary artery (PA) and ascending aorta (AA) diameters has recently been shown to be a useful indicator for disease severity and predictor of outcome in patients with pulmonary hypertension and heart failure. This study aimed at evaluating the applicability of this ratio for perioperative risk assessment of patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary endarterectomy. Methods: In this retrospective cohort study on 149 patients undergoing pulmonary endarterectomy between 2013 and 2020, the preoperative PA to AA ratio was analyzed on axial computed tomography. Variables of pulmonary hemodynamic status were assessed during preoperative right heart catheterization and postoperative Swan-Ganz catheter measurements. Perioperative survival was analyzed by Kaplan-Meier method and log-rank tests. Results: Preoperative computed tomography measurements showed a median AA diameter of 31 mm (range, 19-47 mm), and a median PA diameter of 36 mm (range, 25-55 mm). The calculated median PA to AA ratio was 1.13 (range, 0.79-1.80). PA to AA ratio correlated positively with PA pressure (systolic, r = 0.352 [P < .001]; diastolic, r = 0.406 [P < .001]; mean, r = 0.318 [P < .001]) and inversely with age (r = -0.484 [P < .001]). Univariable Cox regression analysis identified PA diameter (P = .008) as a preoperative parameter predictive of survival. There was a significant difference (log-rank P = .037) in 30-day survival probability for patients with lower PA to AA ratios (<1.136; survival probability, 97.4%) compared with patients with higher ratios (>1.136; survival probability, 88.9%). Conclusions: PA to AA ratio shows a correlation with other variables associated with pulmonary hypertension. In addition, patients with higher PA to AA ratios have lower survival probabilities after PEA. Further analysis of PA to AA ratio on the selection of chronic thromboembolic pulmonary hypertension for different treatment modalities-pulmonary endarterectomy, medical therapy, and or balloon pulmonary angioplasty-is warranted.

Efficacy and Safety of Percutaneous Pulmonary Artery Subtotal Occlusion and Chronic Total Occlusion Intervention in Chronic Thromboembolic Pulmonary Hypertension.

[Figure: see text].

Chronic thromboembolic pulmonary hypertension - still evolving.

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension (PH). The disease is still underdiagnosed, and the true prevalence is unknown. CTEPH is characterized by intraluminal non-resolving thrombus organization and fibrous stenosis, or complete obliteration of pulmonary arteries, promoted by progressive remodeling of the pulmonary vasculature. One consequence of this is an increase in pulmonary vascular resistance and pressure, resulting in PH and progressive right heart failure, leading to death if left untreated. Endovascular disobliteration by pulmonary endarterectomy (PEA) is the preferred treatment for CTEPH patients. PEA surgery is the only technique that can potentially cure CTEPH disease, especially in patients with fresh or organized thrombi of the proximal branches of pulmonary arteries. However, not all patients are eligible for PEA surgery. Recent research has provided evidence suggesting balloon pulmonary angioplasty (BPA) and targeted medical therapy as additional promising available treatments options for inoperable CTEPH and recurrent/persistent PH after PEA surgery. Studies on BPA have shown it to improve pulmonary hemodynamics, symptoms, exercise capacity and RV function in inoperable CTEPH. Subsequently, BPA has developed into an essential component of the modern era of CTEPH treatment. Large randomized controlled trials have demonstrated varying significant improvements with targeted medical therapy in technically inoperable CTEPH patients. Thus, treatment of CTEPH requires a comprehensive multidisciplinary assessment, including an experienced PEA surgeon, PH specialist, BPA interventionist and CTEPH-trained radiologist at expert centers. In this comprehensive review, we address the latest developments in the fast-evolving field of CTEPH. These include advancements in imaging modalities and developments in operative and interventional techniques, which have widened the range of patients who may benefit from these procedures. The efficacy and safety of targeted medical therapies in CTEPH patients are also discussed. As the treatment options for CTEPH improve, hybrid management involving multiple treatments in the same patient may become a viable option in the near future.

Pulmonary artery to ascending aorta ratio by echocardiography: A strong predictor for presence and severity of pulmonary hypertension.

BACKGROUND: The pulmonary artery (PA) to ascending aorta diameter ratio (PA:A) has been evaluated in numerous studies analyzing cardiac magnetic resonance (CMR) and computed tomography (CT) data. Previously, no transthoracic echocardiography (TTE) cutoffs have been published. We sought to evaluate (1) the feasibility to image the pulmonary trunk in a prospective cohort, and (2) the ability of PA:A derived by TTE to predict pulmonary hypertension (PH). METHODS: We performed a post-hoc analysis of a prospectively recruited consecutive cohort of patients referred to our tertiary center cardiology department due to suspicion for PH. Invasive hemodynamic assessment and quasi-simultaneous TTE was performed in all participants. RESULTS: A total of 84 patients were included in the analysis, median age was 70.5 years (IQR 58-75), 46 (55%) were female. The PA was significantly wider in the PH group (28mm vs. 22.5mm, p<0.001) with a resulting median PA:A of 0.84 vs. 0.66 (p<0.001). Both PA diameter (r = 0.524 and r = 0.44, both p<0.001) and PA:A (r = 0.652 and 0.697, both p<0.001) significantly correlated with mPAP and with PVR, respectively. Area under the curve for the detection of PH was 0.853 (95%CI 0.739-0.967, p<0.001). CONCLUSION: The PA can be visualized in almost all echocardiographic exams, especially when it is dilated. A view showing the pulmonary trunk should be included in every routine TTE. An increased PA:A should raise suspicion for PH and prompt further evaluation and follow-up examinations of these patients.

Microvascular Disease in Chronic Thromboembolic Pulmonary Hypertension: Hemodynamic Phenotyping and Histomorphometric Assessment.

BACKGROUND: Pulmonary endarterectomy (PEA) is the gold standard treatment for patients with operable chronic thromboembolic pulmonary hypertension. However, persistent pulmonary hypertension (PH) after PEA remains a major determinant of poor prognosis. A concomitant small-vessel arteriopathy in addition to major pulmonary artery obstruction has been suggested to play an important role in the development of persistent PH and survival after PEA. One of the greatest unmet needs in the current preoperative evaluation is to assess the presence and severity of small-vessel arteriopathy. Using the pulmonary artery occlusion technique, we sought to assess the presence and degree of small-vessel disease in patients with chronic thromboembolic pulmonary hypertension undergoing PEA to predict postoperative outcome before surgery. METHODS: Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure, we partitioned pulmonary vascular resistance in larger arterial (upstream resistance [Rup]) and small arterial plus venous components (downstream resistance) in 90 patients before PEA. For validation, lung wedge biopsies were taken from nonobstructed and obstructed lung territories during PEA in 49 cases. Biopsy sites were chosen according to the pulmonary angiogram still frames that were mounted in the operating room. All vessels per specimen were measured in each patient. Percent media (%MT; arteries) and intima thickness (%IT; arteries, veins, and indeterminate vessels) were calculated relative to external vessel diameter. RESULTS: Decreased Rup was an independent predictor of persistent PH (odds ratio per 10%, 0.40 [95% CI, 0.23-0.69]; P=0.001) and survival (hazard ratio per 10%, 0.03 [95% CI, 0.00-0.33]; p=0.004). Arterial %MT and %IT of nonobstructed lung territories and venous %IT of obstructed lung territories were significantly increased in patients with persistent PH and nonsurvivors. Rup correlated inversely with %MT (r=-0.72, P<0.001) and %IT (r=-0.62, P<0.001) of arteries from nonobstructed lung territories and with %IT (r=-0.44, P=0.024) of veins from obstructed lung territories. Receiver operating characteristic analysis disclosed that Rup <66% predicted persistent PH after PEA, whereas Rup <60% identified patients with poor prognosis after PEA. CONCLUSIONS: Pulmonary artery occlusion waveform analysis with estimation of Rup seems to be a valuable technique for assessing the degree of small-vessel disease and postoperative outcome after PEA in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH): Updated Recommendations from the Cologne Consensus Conference 2018.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subgroup of pulmonary hypertension that differs from all other forms of PH in terms of its pathophysiology, patient characteristics and treatment. For implementation of the European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension in Germany, the Cologne Consensus Conference 2016 was held and last updated in spring of 2018. One of the working groups was dedicated to CTEPH, practical and controversial issues were commented and updated. In every patient with suspected PH, CTEPH or chronic thromboembolic disease (CTED, i.e. symptomatic residual vasculopathy without pulmonary hypertension) should be excluded. Primary treatment is surgical pulmonary endarterectomy (PEA) in a multidisciplinary CTEPH centre. Inoperable patients or patients with persistent or recurrent CTEPH after PEA are candidates for targeted drug therapy. There is increasing experience with balloon pulmonary angioplasty (BPA) for inoperable patients; this option, like PEA, is reserved for specialised centres with expertise in this treatment method.

Usefulness of thrombosis and inflammation biomarkers in chronic thromboembolic pulmonary hypertension-sampling plasma and surgical specimens.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) results from persistent pulmonary vascular obstructions, presumably due to inflammatory thrombosis. Because estimates of thrombus volume at diagnosis have no predictive value, we investigated the role of the thrombosis marker, D-dimer, and the inflammation marker, C-reactive protein (CRP), for predicting outcomes in CTEPH. METHODS: A total 289 consecutive patients with CTEPH were followed for 57 (median 45 to 69) months. One hundred fifty-seven of these patients underwent surgical pulmonary endarterectomy (PEA). D-dimer and CRP were collected at the time of CTEPH diagnosis and their impact on outcome was analyzed using Cox and logistic regression models. Their association with thrombus composition was analyzed utilizing HistoQuest. RESULTS: D-dimer and CRP levels were separately and independently predictive of death or need for lung transplantation (p = 0.012 and p = 0.025, respectively). For example, 5-year survival was 90% (confidence limits 84% to 96%) in patients with D-dimer levels <0.5 µg/ml and CRP <1 mg/dl at diagnosis, as compared with 50% (36% to 64%) for patients with D-dimer ≥0.5 µg/ml and CRP ≥1 mg/dl (p < 0.001). D-dimer and CRP both decreased significantly after PEA (p < 0.01). The amount of fresh red thrombus in thrombendarterectomy specimens correlated positively with D-dimer levels at diagnosis (r = 0.37, p = 0.003). CONCLUSIONS: D-dimer and CRP at the time of diagnosis are independent and significant predictors of outcome in CTEPH, available at the time of diagnosis. This observation suggests an important role for fibrin turnover and inflammation in the pathogenesis of CTEPH and the associated complications.

In-depth haemodynamic phenotyping of pulmonary hypertension due to left heart disease.

The commonest cause of pulmonary hypertension (PH) is left heart disease (LHD). The current classification system for definitions of PH-LHD is under review. We therefore performed prospective in-depth invasive haemodynamic phenotyping in order to assess the site of increased pulmonary vascular resistance (PVR) in PH-LHD subsets.Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure, we partitioned PVR in larger arterial (Rup, upstream resistance) and small arterial plus venous components (Rds, downstream resistance). In the case of small vessel disease, Rup decreases and Rds increases. Inhaled nitric oxide (NO) testing was used to assess acute vasoreactivity.Right ventricular afterload (PVR, pulmonary arterial compliance and effective arterial elastance) was significantly higher in combined post- and pre-capillary PH (Cpc-PH, n=35) than in isolated post-capillary PH (Ipc-PH, n=20). Right ventricular afterload decreased during inhalation of NO in Cpc-PH and idiopathic pulmonary arterial hypertension (n=31), but remained unchanged in Ipc-PH. Rup was similar in Cpc-PH (66.8±10.8%) and idiopathic pulmonary arterial hypertension (65.0±12.2%; p=0.530) suggesting small vessel disease, but significantly higher in Ipc-PH (96.5±4.5%; p<0.001) suggesting upstream transmission of elevated left atrial pressure.Right ventricular afterload is driven by elevated left atrial pressure in Ipc-PH and is further increased by elevated small vessel resistance in Cpc-PH. Cpc-PH is responsive to inhaled NO. Our data support current definitions of PH-LHD subsets.

Subcutaneous treprostinil in congenital heart disease-related pulmonary arterial hypertension.

OBJECTIVE: To assess the efficacy and safety of subcutaneous treprostinil in adult patients with congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after 12 months of treatment. METHODS: Consecutive adult patients with CHD-PAH received subcutaneous treprostinil to maximum tolerated doses in an observational study. RESULTS: Advanced CHD-PAH patients with WHO class III or IV disease (n=32, age 40±10 years, 20 females) received treprostinil for suboptimal response to bosentan (n=12), WHO functional class IV disease (FC, n=7) or prior to bosentan approval (n=13). In the multivariate mixed model, mean increase in 6 min walk distance (6-MWD) from baseline to 12 months was 114 m (76; 152) (P<0.001). WHO FC improved significantly (P=0.001) and B-type brain natriuretic peptide decreased from 1259 (375; 2368) pg/mL to 380 (144; 1468) pg/mL (P=0.02). In those 14 patients who had haemodynamic data before and after initiation of treprostinil, pulmonary vascular resistance decreased significantly (from 18.4±11.1 to 12.6±7.9 Wood units, P=0.003). The most common adverse events were infusion-site erythema and pain. One patient stopped treatment because of intolerable infusion-site pain after 8 months of treatment. No other major treatment-related complications were observed. Five patients died during early follow-up, having experienced a decrease in their 6-MWD prior. CONCLUSIONS: Subcutaneous treprostinil therapy is generally safe and effective for at least 12 months and may be used in CHD-related PAH class III and IV.

Multi-view approach for the diagnosis of pulmonary hypertension using transthoracic echocardiography.

Pulmonary hypertension (PH) is a disease with severe morbidity and mortality. Echocardiography plays an essential role in the screening of PH. The quality of the acquired continuous wave Doppler signal is the major limitation of the method and can greatly affect the accuracy of estimated pulmonary pressures. The aim of this study was to evaluate the clinical need to image from multiple ultrasound windows in patients with suspected pulmonary hypertension. We prospectively evaluated 65 patients (43% male, mean age 67.2 years) with echocardiography and right heart catheterization. 17% had invasively normal pulmonary pressures, 83% had pulmonary hypertension. Peak tricuspid regurgitation (TR) velocity was imaged in five echocardiographic views. Sufficient Doppler signal was recorded in 94% of the patients. Correlation for overall peak TR velocity with invasively measured systolic pulmonary artery pressure was r = 0.83 (p < 0.001). Considering all five imaging windows resulted in a sensitivity of 87%, and a specificity of 91% for correct diagnosis of PH with an AUC of 0.89, which was significantly better as compared to sole imaging from the right ventricular modified apical four-chamber view (AUC 0.85, p = 0.0395). Additional imaging from atypical views changed the overall peak TR velocity in 32% of the patients. A multiple-view approach changed the echocardiographic diagnosis of PH in 11% of the patients as opposed to sole imaging from an apical four-chamber view. This study comprehensively assessed the impact on clinical decision making when evaluating patients with an echocardiographic multiplane approach for suspected PH. This approach substantially increased sensitivity without a decrease in specificity.

Hemodynamic Phenotyping of Pulmonary Hypertension in Left Heart Failure.

Increased pulmonary venous pressure secondary to left heart disease is the most common cause of pulmonary hypertension (PH). The diagnosis of PH due to left heart disease relies on a clinical probability assessment followed by the invasive measurements of a mean pulmonary artery pressure (PAP) ≥25 mm Hg and mean wedged PAP (PAWP) >15 mm Hg. A combination of mean PAP and mean PAWP defines postcapillary PH. Postcapillary PH is generally associated with a diastolic pulmonary pressure gradient (diastolic PAP minus mean PAWP) <7 mm Hg, a transpulmonary pressure gradient (mean PAP minus mean PAWP) <12 mm Hg, and pulmonary vascular resistance ≤3 Wood units (WU). This combination of criteria defines isolated postcapillary PH. Postcapillary PH with elevated vascular gradients and pulmonary vascular resistance defines combined post- and precapillary PH (Cpc-PH). Postcapillary PH is associated with a decreased survival in proportion to increased pulmonary vascular gradients, decreased pulmonary arterial compliance, and reduced right ventricular function. The Cpc-PH subcategory occurs in 12% to 13% of patients with PH due to left heart disease. Patients with Cpc-PH have severe PH, with higher diastolic pulmonary pressure gradient, transpulmonary pressure gradient, and pulmonary vascular resistance and more pronounced ventilatory responses to exercise, lower pulmonary arterial compliance, depressed right ventricular ejection fraction, and shorter life expectancy than isolated postcapillary PH. Cpc-PH bears similarities to pulmonary arterial hypertension. Whether Cpc-PH is amenable to therapies targeting the pulmonary circulation remains to be tested by properly designed randomized controlled trials.

Hemodynamic Thresholds for Precapillary Pulmonary Hypertension.

BACKGROUND: Hemodynamic differentiation between pulmonary arterial hypertension (PAH) and postcapillary pulmonary hypertension (PH) is important because treatment options are strikingly different for the two disease subsets. Whereas patients with PAH can be treated effectively with targeted therapies, their use in postcapillary PH is currently not recommended. Our aim was to establish an algorithm to identify patients who are likely to experience a significant hemodynamic treatment response. METHODS: We determined hemodynamic cutoffs to discriminate between idiopathic PAH and postcapillary PH in a large database of 4,363 stable patients undergoing first diagnostic right and left heart catheterizations. In a second step, we performed a patient-level pooled analysis of four randomized, placebo-controlled trials including 541 patients with PAH who received treprostinil or placebo, to validate hemodynamic cutoffs with regard to treatment response. RESULTS: Receiver operating characteristic analysis identified mean pulmonary arterial wedge pressure (mPAWP) < 12 mm Hg and diastolic pulmonary vascular pressure gradient (DPG) ≥ 7 mm Hg as the best hemodynamic discriminators between idiopathic PAH and postcapillary PH. In our treatment study, only patients with mPAWP < 12 mm Hg, DPG > 20 mm Hg or a combination of both had a significant placebo-corrected improvement in hemodynamics. CONCLUSIONS: mPAWP < 12 mm Hg and DPG > 20 mm Hg identify patients with PAH who are likely to have significant hemodynamic improvement with prostacyclin treatment.

Pulmonary Hypertension in Heart Failure. Epidemiology, Right Ventricular Function, and Survival.

RATIONALE: Patients with pulmonary hypertension due to left heart disease (PH-LHD) and a diastolic pulmonary vascular pressure gradient ≥ 7 mm Hg, representing PH out of proportion to pulmonary arterial wedge pressure, have pulmonary vascular disease and increased mortality. Little information exists on this condition, recently labeled as "combined pre- and post-capillary PH" (Cpc-PH). OBJECTIVES: To investigate epidemiology, risk factors, right ventricular function, and outcomes in patients with chronic heart failure and Cpc-PH. METHODS: The study population was identified from a retrospective chart review of a clinical database of 3,107 stable patients who underwent first diagnostic right heart catheterization and from a prospective cohort of 800 consecutive patients at a national university-affiliated tertiary center. MEASUREMENTS AND MAIN RESULTS: The retrospective cohort had 664 patients with systolic heart failure (SHF) and 399 patients with diastolic heart failure (DHF), 12% of whom were classified as Cpc-PH. The prospective cohort had 172 patients with SHF (14% Cpc-PH) and 219 patients with DHF (12% Cpc-PH). Chronic obstructive pulmonary disease (P = 0.034) and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio (P = 0.015) predicted Cpc-PH in SHF. Younger age (P = 0.004), valvular heart disease (P = 0.046), and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio predicted Cpc-PH in DHF (P = 0.016). Right ventricular-pulmonary vascular coupling was worse in Cpc-PH patients (end-systolic elastance to effective arterial elastance [Ees/Ea]: SHF: 1.05 ± 0.25; P = 0.002; DHF: 1.17 ± 0.27; P = 0.027) than in those with isolated post-capillary PH (Ees/Ea: SHF: 1.52 ± 0.51; DHF: 1.45 ± 0.29). CONCLUSIONS: Cpc-PH is rare in chronic heart failure. Right ventricular-pulmonary vascular coupling is poor in Cpc-PH and could be one explanation for dismal outcomes.

Advanced imaging tools rather than hemodynamics should be the primary approach for diagnosing, following, and managing pulmonary arterial hypertension.

Pulmonary hypertension (PH) is currently defined based on invasive measurements: a resting pulmonary artery pressure ≥ 25 mm Hg. For pulmonary arterial hypertension, a pulmonary arterial wedge pressure ≤ 15 mm Hg and pulmonary vascular resistance > 3 Wood units are also required. Thus, right heart catheterization is inevitable at present. However, the diagnosis, follow-up, and management of PH by noninvasive techniques is progressing. Significant advances have been achieved in the imaging of pulmonary vascular disease and the right ventricle. We review the current sensitivities and specificities of noninvasive imaging of PH and discuss its role and future potential to replace hemodynamics as the primary approach to screening, diagnosing, and following/managing PH.

Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in "out-of-proportion" pulmonary hypertension.

BACKGROUND: Left-sided heart disease (LHD) is the most common cause of pulmonary hypertension (PH). In patients with LHD, elevated left atrial pressure causes a passive increase in pulmonary vascular pressure by hydrostatic transmission. In some patients, an active component caused by pulmonary arterial vasoconstriction and/or vascular remodeling superimposed on left-sided pressure elevation is observed. This "reactive" or "out-of-proportion" PH, defined as PH due to LHD with a transpulmonary gradient (TPG) > 12 mm Hg, confers a worse prognosis. However, TPG is sensitive to changes in cardiac output and left atrial pressure. Therefore, we tested the prognostic value of diastolic pulmonary vascular pressure gradient (DPG) (ie, the difference between invasive diastolic pulmonary artery pressure and mean pulmonary capillary wedge pressure) to better prognosticate death in "out-of-proportion" PH. METHODS: A large database of consecutive cases was analyzed. One thousand ninety-four of 2,351 complete data sets were from patients with PH due to LHD. For proof of concept, available lung histologies were reviewed. RESULTS: In patients with postcapillary PH and a TPG > 12 mm Hg, a worse median survival (78 months) was associated with a DPG ≥ 7 mm Hg compared with a DPG < 7 mm Hg (101 months, P = .010). Elevated DPG was associated with more advanced pulmonary vascular remodeling. CONCLUSIONS: DPG identifies patients with "out-of-proportion" PH who have significant pulmonary vascular disease and increased mortality. We propose a diagnostic algorithm, using pulmonary capillary wedge pressure, TPG, and DPG in sequence to diagnose pulmonary vascular disease superimposed on left-sided pressure elevation.