Combined Pre- And Post-capillary PH Research Articles

Transcriptome-wide analysis associates ID2 expression with combined pre- and post-capillary pulmonary hypertension

Heart failure with preserved ejection fraction (HFpEF) patients who develop pulmonary hypertension (PH) have an increased risk of death, with combined pre- and post-capillary PH (CpcPH) having the highest risk. However, the mechanism behind PH development in HFpEF is poorly understood. We aimed to identify transcriptomic associations with PH development in HFpEF. Blood was collected from 30 HFpEF patients: 10 without PH, 10 with isolated post-capillary PH, and 10 with CpcPH. Gene expression measurements were completed using transcriptome-wide RNA sequencing. Gene expression differences were compared using a quasi-likelihood method adjusting for age, sex, race, and smoking-status. Biological pathways were compared using global gene expression differences. A replication in 34 additional heart failure patients and a validation in lung tissue from a representative mouse model were completed using quantitative PCR. Six differentially expressed genes were identified when comparing transcriptomics between subjects with CpcPH and those without PH. When tested in additional subjects, only the association with ID2 replicated. Consistent with clinical findings, Id2 expression was also upregulated in mice with HFpEF and PH. Pathway analysis identified proliferative and mitochondrial pathways associated with CpcPH. Thus, these patients may possess systemic pathophysiological differences similar to those observed in pulmonary arterial hypertension patients.

Association Between Right Ventricular Contractile Function and Cardiac Events in Isolated Postcapillary and Combined Pre- and Postcapillary Pulmonary Hypertension

BackgroundRecent studies have shown that patients with combined pre- and postcapillary pulmonary hypertension (CpcPH) had worse outcomes than those with isolated postcapillary pulmonary hypertension (IpcPH). However, the prognostic factors including right ventricular (RV) function have not been well documented. The aim of this study was to assess the differentiation of PH phenotypes, using echocardiography, and the association between RV longitudinal strain and cardiac events. Methods and ResultsWe prospectively recruited consecutive patients who had undergone right heart catheterization. The primary endpoint was cardiovascular death or readmission due to heart failure. We included 137 patients with Group 2 PH. A RV longitudinal strain of 17% was sensitive (85%) and specific (70%) to determine the CpcPH. During a median period of 31 months, 43 patients experienced the primary endpoint during follow-up. In a multivariate analysis, RV longitudinal strain was associated with the primary endpoint in both CpcPH and IpcPH (HR: 0.84, P = 0.003; HR: 0.86, P = 0.001). ConclusionsLower RV longitudinal strain was independently associated with worse outcomes in CpcPH and IpcPH. RV longitudinal strain may play a prognostic role in PH phenotypes.

Hemodynamic Effects of Pulmonary Arterial Hypertension-Specific Therapy in Patients With Heart Failure With Preserved Ejection Fraction and With Combined Post- and Precapillay Pulmonary Hypertension

Drugs approved for pulmonary arterial hypertension have been considered for patients with heart failure with preserved ejection fraction and combined post- and precapillary pulmonary hypertension (Cpc-PH). We aimed to study changes in cardiac volumes, cardiac load and left ventricular (LV) filling pressures in patients with heart failure with preserved ejection fraction and Cpc-PH in response to pulmonary arterial hypertension-specific treatment. In this prospective study, 23 patients with heart failure with preserved ejection fraction and Cpc-PH underwent right-heart catheterization, including acute provocation testing (fluid loading and inhaled nitric oxide) and cardiac MRI at baseline. Right-heart catheterization and cardiac MRI were repeated after 4 months of treatment. At baseline, acutely increasing preload by fluid loading resulted in a significant increase in pulmonary arterial wedge pressure (PAWP), whereas reducing right ventricular (RV) afterload and increasing LV distensability by acute administration of inhaled nitric oxide had no effect on PAWP. After 4 months of treatment, we observed a significant reduction in RV and LV afterload and increased RV and LV stroke volume, but PAWP significantly increased. In patients with heart failure with preserved ejection fraction and Cpc-PH, 4 months of pulmonary arterial hypertension-specific treatment increased RV and LV stroke volume at the expense of increased PAWP. This increase in PAWP was similarly observed acutely after fluid loading.

Pulmonary hypertension in HFpEF and HFrEF: Pathophysiology, diagnosis, treatment approaches.

Pulmonary hypertension (PH) is afrequent hemodynamic condition that is highly prevalent in patients with heart failure and reduced (HFrEF) or preserved ejection fraction (HFpEF). Irrespective of left ventricular EF, the presence of PH and right ventricular (RV) dysfunction are highly relevant for morbidity and mortality in patients with heart failure. While elevated left-sided filling pressures and functional mitral regurgitation primarily lead to post-capillary PH, current guidelines and recommendations distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH), the latter being defined by apulmonary vascular resistance (PVR) of ≥3Wood units. Here, we describe the pathophysiology and clinical relevance of these distinct entities, and report on the diagnostic work-up including remote pulmonary artery pressure (PAP) monitoring. Furthermore, we highlight strategies to manage PH and improve RV function in heart failure, which may include optimized management of HFrEF and HFpEF (medical and interventional), sufficient volume control, catheter-based mitral valve repair, and-in selected cases-targeted PH therapy. In this context, we also highlight gaps in evidence and the need for further research.

Doppler estimates of pulmonary vascular resistance to phenotype pulmonary hypertension in heart failure

An accurate distinction between isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post- and pre-capillary pulmonary hypertension (Cpc-PH) is integral to therapy and prognosis in heart failure (HF). This study aimed to compare the ability of four previously validated Doppler estimates of pulmonary vascular resistance (PVRDoppler) to distinguish Ipc-PH from Cpc-PH in a well-defined HF population. Consecutive subjects referred for HF assessment underwent standard echocardiography immediately followed by right heart catheterization (RHC). Subjects with atrial fibrillation, acute coronary syndrome, significant valvular disease or poor image quality were excluded. PVRDoppler estimates were correlated with invasive PVR and agreement was studied using Bland–Altman analysis. Receiver operating characteristics analyses were performed to determine the ability of PVRDoppler methods to identify PVR > 3WU. 55 HF subjects (58 ± 16 years, 55% Ipc-PH) were analyzed. PVRDoppler estimates demonstrated weak to modest associations with invasive PVR. The Doppler method proposed by Abbas et al. demonstrated relatively strong discriminatory ability to distinguish Ipc-PH from Cpc-PH (AUC = 0.79; 95% CI 0.63–0.96; p = 0.001). However, Bland–Altman analysis revealed wide limits of agreement (bias = 0; SD = 1.83WU) and greater variability at higher mean PVR. Conclusions: PVRDoppler estimates demonstrate reasonable ability to distinguish Ipc-PH from Cpc-PH but may not be reliable independent PH distinguishers in HF.

Prognostic value and diagnostic properties of the diastolic pulmonary pressure gradient in patients with pulmonary hypertension and left heart disease

BackgroundThe use of the diastolic pressure gradient (DPG) for the diagnosis of combined post- and pre-capillary pulmonary hypertension (Cpc-PH) versus isolated post-capillary pulmonary hypertension (Ipc-PH) in patients with PH due to left heart disease (PH-LHD) remains controversial. We studied the incremental prognostic information provided by DPG and potential sources of disagreements between different hemodynamic criteria for Cpc-PH. MethodsWe studied 393 patients with PH-LHD who underwent right heart catheterization and were followed for hospitalizations and all-cause mortality for a median of 53 months. Patients were classified into Ipc-PH or Cpc-PH using DPG, pulmonary vascular resistance (PVR) or transpulmonary gradient (TPG)-based criteria. ResultsClassifying PH categories according to DPG alone was not associated with a significant difference in clinical outcomes between patients with Ipc-PH and Cpc-PH (P = 0.17). By contrast, PVR criteria alone were associated with a strong prognostic separation between Ipc-PH and Cpc-PH (P = 0.005). Adding DPG to the PVR-based classification contributed no additional prognostic information. Classifying PH using the cutoff of DPG >7 mmHg or TPG >15 mmHg, resulted in an almost perfect agreement (κ statistic 0.87; 93.4% agreement). However, in cases of disagreement, occurring with low or negative DPG values, the TPG-based classification was more likely to be correct. ConclusionThe DPG does not add incremental prognostic information beyond PVR. Using DPG/PVR criteria to differentiate between Ipc-PH and Cpc-PH is equivalent to using TPG/PVR criteria with a TPG threshold >15 mmHg. However, the use of DPG for diagnostic purposes may lead to misclassification of PH when DPG is low or negative.

Echocardiographic determination of pulmonary arterial capacitance.

A growing body of evidence has demonstrated that pulmonary arterial capacitance (PAC) is the strongest hemodynamic predictor of clinical outcomes across a wide spectrum of cardiovascular disease, including pulmonary hypertension and heart failure. We hypothesized that a ratio of right ventricular stroke volume (RVOT VTI) to the associated peak arterial systolic pressure (PASP) could function as a reliable non-invasive surrogate for PAC. We performed a prospective study of patients undergoing simultaneous transthoracic echocardiography and right heart catheterization (RHC) for various clinical indications. Measurements of the RVOT VTI/PASP ratio from echocardiographic measurements were compared against PAC calculated from RHC measurements. Correlation coefficients and Bland-Altman analysis compared the RVOT VTI/PASP ratio with PAC. Forty-five subjects were enrolled, 38% were female and mean age was 54years (SD 13years). The reason for referral to RHC was most commonly post-heart transplant surveillance (40%), followed by heart failure (22%), and pulmonary hypertension (18%). Pre-capillary pulmonary hypertension was present in 18%, isolated post-capillary pulmonary hypertension was present in 13%, and combined pre-and post-capillary pulmonary hypertension was present in 29%. The RVOT VTI/PASP ratio was obtainable in the majority of patients (78%), and Pearson's correlation demonstrated moderately-strong association between PAC and the RVOT VTI/PASP ratio, r = 0.75 (P < 0.001). Bland-Altman analysis demonstrated good agreement between measurements without suggestion of systematic bias and a mean difference in standardized units of - 0.133. In a diverse population of patients and hemodynamic profiles, we validated that the ratio of RVOT VTI/PASP to be a reliably-obtained non-invasive marker associated with PAC.

Secular Trends and Outcome of Isolated versus Combined Type 2 Pulmonary Hypertension in Patients with End-Stage Heart Failure

Purpose The presence of pulmonary hypertension (PH) is associated with some adverse outcomes following cardiac transplantation (CTx). It is now suggested to diagnose group 2 PH when the mean pulmonary artery pressure (PAPm) is >20 mmHg. The characteristics and outcomes of patients with isolated post-capillary PH (Ipc-PH) versus combined pre- and post-capillary PH (Cpc-PH) diagnosed pre-CTx using this new definition and follow-up long-term after CTx have not been investigated. Methods This study included 361 patients who received a first CTx at the Montreal Heart Institute between January 1983 and December 2014. Patients were classified as having PH based on the most recent right heart catheterization prior to CTx. Ipc-PH was defined by a pulmonary capillary wedge pressure (PCWP) >15 mmHg, PAPm >20 mmHg and pulmonary vascular resistance (PVR) ≤3 woods units, while Cpc-PH was defined by a PCWP >15 mmHg, PAPm >20 mmHg and PVR >3 woods units. Severe PH was defined as PAPm ≥35 mmHg. The cohort was analyzed in 2 groups according to the era of CTx (first: 1983 to 1998; second: 1999 to 2014). The primary outcome was all cause and cardiovascular mortality. The secondary outcomes included a selection of major adverse cardiac events. Results The prevalence of PH was 90.71% in the first era (Ipc-PH=55.19% and Cpc-PH=35.52%) versus 83.71% in the second era (Ipc-PH=49.44% and Cpc-PH=34.27%); P=NS. Both severe Cpc-PH and severe Ipc-PH were less prevalent in the second era (20.22% vs 30.05% Cpc-PH and 16.29% vs 25.14% Ipc-PH; P=0.0016). However, there were no significant changes in PAPm values for all severity of Ipc-PH or Cpc-PH across the eras. The diagnosis of Ipc-PH or Cpc-PH yielded no impact on intra-hospital or 30 days mortality regardless of era of CTx. However, severe PH (severe Ipc-PH or Cpc-PH combined) was associated with an increased 30 days, 1 year and 3 years mortality (all P Conclusion The prevalence of Ipc-PH or Cpc-PH is very high pre-CTx. Unless severe, the presence of group 2-PH has not modulated the early or late post-CTx mortality over 30 years. Accurate diagnosis and better treatments for severe PH pre-CTx are needed to improve outcome in these high-risk patients.

Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension

ObjectiveHeart failure with preserved ejection fraction (HFpEF) is frequently associated with pulmonary hypertension (PH), which substantially impacts survival. Based on pulmonary vascular resistance (PVR) and the diastolic pressure gradient (DPG), current guidelines distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). However, the therapeutic consequences of this sub-classification remain entirely unclear. We specifically investigated the efficacy and safety of PDE5i in patients with HFpEF and CpcPH. MethodsIn 40 hemodynamically precisely characterized patients with HFpEF and Cpc-PH who were treated with a PDE5i for at least 12 months, the therapeutic effect on 6-minute walk distance (6MWD), WHO functional class (FC), NTproBNP levels, right ventricular function, and hospitalization rates was evaluated. ResultsPatients' mean age was 73 ± 9 years, and comorbidities were frequent (78% hypertension, 58% atrial fibrillation, 35% diabetes). Initially, 38 patients (95%) were in WHO-FC III and 2 patients (5%) in WHO-FC II. Prior to PDE5i initiation, mean PAPm was 46.2 ± 10.3 mmHg, PAWP 21.2 ± 4.7 mmHg, DPG 5.5 ± 7.2 mmHg, and PVR 6.2 ± 3.0 WU. After 12 months of PDE5i therapy, the 6MWD increased from initially 277 ± 17 to 340 ± 18 m (p < 0.001), and the proportion of patients in WHO-FC I/II increased from 5% to 37.5%. NTproBNP levels decreased by 33% (p = 0.004), and TAPSE improved from 16.8 ± 0.7 mm at baseline to 18.2 ± 0.6 mm (p = 0.01). The rate of HF-associated hospitalizations was substantially lower in the 12 months post PDE5i initiation compared to the prior 12 months. The DPG had no impact on the response to therapy. No deaths occurred, and typical side effects of PDE5i were observed. ConclusionThese data indicate that at least a subset of precisely characterized patients with HFpEF and CpcPH who tolerate PDE5i may benefit from targeted therapy. A randomized study in this particular sub-population is warranted.

Pulmonary Artery Denervation Significantly Increases 6-Min Walk Distance for Patients With Combined Pre- and Post-Capillary Pulmonary Hypertension Associated With Left Heart Failure: The PADN-5 Study

ObjectivesThe authors sought to assess the benefits of pulmonary artery denervation (PADN) among combined pre- and post-capillary pulmonary hypertension (CpcPH) patients in a prospective, randomized, sham-controlled trial. BackgroundPADN has been shown to improve hemodynamics of pulmonary arterial hypertension in a series of patients. Additionally, benefits of targeted medical therapy for patients with CpcPH secondary to left-sided heart failure are unknown. MethodsNinety-eight CpcPH patients, defined as mean pulmonary arterial pressure ≥25 mm Hg, pulmonary capillary wedge pressure >15 mm Hg, and pulmonary vascular resistance (PVR) >3.0 Wood units (WU), were randomly assigned to PADN or sildenafil plus sham PADN. Standard medical therapy for heart failure was administered to all patients in both groups. The primary endpoint was the increase in the 6-min walk distance at the 6-month follow-up. The secondary endpoint was change in PVR. Clinical worsening was assessed in a post hoc analysis. The main safety endpoint was occurrence of pulmonary embolism. ResultsAt 6 months, the mean increases in the 6-min walk distance were 83 m in the PADN group and 15 m in the sildenafil group (least square mean difference 66 m, 95% confidence interval: 38.2 to 98.8 m; p < 0.001). PADN treatment was associated with a significantly lower PVR than in the sildenafil group (4.2 ± 1.5 WU vs. 6.1 ± 2.9 WU; p = 0.001). Clinical worsening was less frequent in the PADN group compared with the sildenafil group (16.7% vs. 40%; p = 0.014). At the end of the study, there were 7 all-cause deaths and 2 cases of pulmonary embolism. ConclusionsPADN is associated with significant improvements in hemodynamic and clinical outcomes in patients with CpcPH. Further studies are warranted to define its precise role in the treatment of this patient population. (Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure [PADN-5]; NCT02220335)

Pulmonary hypertension associated with left heart disease: Updated Recommendations of the Cologne Consensus Conference 2018

In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH associated with left heart disease. In this context, the European Guidelines point out that the drugs currently approved to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, sGC stimulators) have not sufficiently been investigated in other forms of PH. However, despite the lack of respective efficacy data, an uncritical use of targeted PAH drugs in patients with PH associated with left heart disease is currently observed at an increasing rate. This development is a matter of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease. In that sense, the distinction between isolated post-capillary pulmonary hypertension (IpcPH) and combined post- and pre-capillary pulmonary hypertension (CpcPH) and their proper definition may be of particular relevance. The detailed results and recommendations of the working group on PH associated with left heart disease, which were last updated in the spring of 2018, are summarized in this article.

Identifying At-Risk Patients with Combined Pre- and Postcapillary Pulmonary Hypertension Using Interventricular Septal Angle at Cardiac MRI.

PurposeTo assess interventricular septal (IVS) angle in the identification of combined pre- and postcapillary pulmonary hypertension (Cpc-PH) in patients with pulmonary hypertension (PH) due to left-sided heart disease.Materials and MethodsIn this retrospective study, consecutive, incident patients suspected of having PH underwent same-day right-sided heart catheterization (RHC) and MRI at a PH referral center between April 2012 and April 2017. The diagnostic accuracy of the IVS angle to identify Cpc-PH in patients with pulmonary arterial wedge pressure (PAWP) greater than 15 mmHg was assessed by using receiver operator characteristic curves, sensitivity, specificity, and negative and positive predictive values. IVS angle also was assessed as a predictor of all-cause mortality by using Cox uni- and multivariable proportional hazards regression.ResultsA total of 708 patients underwent same-day MRI and RHC, and 171 patients had PAWP greater than 15 mmHg. Mean age was 70 years (range, 21–90 years) (women: mean age, 69 years; range, 21–88 years) (men: mean age, 71 years; range, 43–90 years). Systolic IVS angle correlated with diastolic pulmonary gradient (DPG) (r = 0.739, P < .001). Receiver operating characteristic curve analysis showed septal angle enabled identification of Cpc-PH (DPG ≥ 7), with an area under the receiver operating characteristic curve of 0.911 (P < .001). A 160° threshold, derived from the first half of patients with raised PAWP, enabled identification of a DPG of at least 7 mmHg with 67% sensitivity and 93% specificity (P < .001) in the second cohort of patients with raised PAWP. IVS angle was predictive of all-cause mortality (standardized univariable hazard ratio, 1.615; P < .01).ConclusionThe systolic interventricular septal angle is elevated in patients with combined pre- and postcapillary pulmonary hypertension and enables one to predict those patients who have PH due to left-sided heart disease who have an increased risk of death.Published under a CC BY 4.0 license.Online supplemental material is available for this article.

Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients.

The biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role of NOS in HF-PH. DNA samples from 118 patients with HF-PH were genotyped for the NOS3 rs1799983 and NOS2 rs3730017 polymorphisms. A multiple regression model was used to compare hemodynamic measurements between genotype groups. Patients with the T/T genotype at rs1799983 possessed a nearly 10 mmHg increased transpulmonary gradient (TPG) compared to those with other genotypes (P = 0.006). This finding was replicated in an independent cohort of 94 HF-PH patients (P = 0.005). However, when tested in a cohort of 162 pre-capillary pulmonary arterial hypertension patients, no association was observed. In a combined analysis of both HF-PH cohorts, mean pulmonary artery pressure (mPAP), diastolic pulmonary gradient (DPG), and CpcPH status were also associated with rs1799983 genotype (P = 0.005, P = 0.03, and P = 0.02, respectively). In patients with HF-PH, the NOS3 rs1799983 polymorphism is associated with TPG, and potentially mPAP and DPG as well. These findings suggest that endothelial NOS (encoded by NOS3) may be involved in the pulmonary vascular remodeling observed in Cpc-PH and warrants further study.

High Right Ventricular Stroke Work Index Is Associated with Worse Kidney Function in Patients with Heart Failure with Preserved Ejection Fraction

Background: In patients with heart failure with preserved ejection fraction (HFpEF), worse kidney function is associated with worse overall cardiac mechanics. Right ventricular stroke work index (RVSWI) is a parameter of right ventricular function. The aim of our study was to determine the relationship between RVSWI and glomerular filtration rate (GFR) in patients with HFpEF. Method: This was a single-center cross-sectional study. HFpEF is defined as patients with documented heart failure with ejection fraction > 50% and pulmonary wedge pressure > 15 mm Hg from right heart catheterization. RVSWI (normal value 8–12 g/m/beat/m²) was calculated using the formula: RVSWI = 0.0136 × stroke volume index × (mean pulmonary artery pressure – mean right atrial pressure). Univariate and multivariate linear regression analysis was performed to study the correlation between RVSWI and GFR. Result: Ninety-one patients were included in the study. The patients were predominantly female (n = 64, 70%) and African American (n = 61, 67%). Mean age was 66 ± 12 years. Mean GFR was 59 ± 35 mL/min/1.73 m². Mean RVSWI was 11 ± 6 g/m/beat/m². Linear regression analysis showed that there was a significant independent inverse relationship between RVSWI and GFR (unstandardized coefficient = –1.3, p = 0.029). In the subgroup with combined post and precapillary pulmonary hypertension (Cpc-PH) the association remained significant (unstandardized coefficient = –1.74, 95% CI –3.37 to –0.11, p = 0.04). Conclusion: High right ventricular workload indicated by high RVSWI is associated with worse renal function in patients with Cpc-PH. Further prospective studies are needed to better understand this association.

P2-4 - Clinical Background in Patients With Pulmonary Hypertension Due to Left Heart Disease

Background: Pulmonary hypertension (PH) is a relevant complication of left heart disease (LHD). The 2015 ESC/ERS PH guidelines report two different hemodynamic phenotypes of PH due to LHD (PH-LHD) based on pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG): isolated post-capillary PH (Ipc-PH) and combined post- and pre-capillary PH (Cpc-PH). The objective of this study is to reveal the clinical characterics of Ipc-PH and Cpc-PH. Methods and Results: Among 184 consecutive chronic heart failure patients (averaged age: 64 y.o) who underwent right heart catheterization in our hospital, 62 patients (34%) were identified as PH-LHD. According to the guidelines, Ipc-PH is defined by DPG <7 mmHg and/or PVR ≦ 3 WU and Cpc-PH by DPG ≧ 7 mmHg and/or PVR > 3 WU. Using this definition, we identified three patient groups: Ipc-PH with both normal PVR and DPG (34 pts); Cpc-PH with both increased PVR and DPG (6 pts); and an intermediate group with either increased PVR or DPG (22 pts). Patients with Cpc-PH and the intermediate group had significantly higher mean PA pressure (40 ± 9 vs 31 ± 5 mmHg, P < .001) and lower SvO2 (60 ± 5 vs 69 ± 7%, P < .001) and lower cardiac output compared with the group of patients with Ipc-PH. LVEF in Cpc-PH and the intermediate group tend to be lower than Ipc-PH. Conclusion: Patients with Cpc-PH and the intermediate group have severe clinical background than those with Ipc-PH.

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.

Septal angle on MRI predicts combined pre- and post-capillary pulmonary hypertension

Purpose: Patients with left heart disease commonly develop pulmonary hypertension (PH), and some subsequently develop pre-capillary vascular remodelling. This combined pre- and post-capillary pulmonary hypertension (Cpc-PH) is defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg, pulmonary arterial wedge pressure (PAWP) >15 mmHg and diastolic pulmonary gradient (DPG) of ≥7. Patients with Cpc-PH have a worse outcome and targeted pulmonary vascular therapies may be useful. The aim of this study was to assess the role of magnetic resonance imaging (MRI) septal angle in Cpc-PH.

P2587Therapeutic effects of phosphodiesterase 5 inhibitors in patients with heart failure with preserved ejection fraction (HFpEF) and combined post- and pre-capillary pulmonary hypertension (Cpc-PH)

P2587Therapeutic effects of phosphodiesterase 5 inhibitors in patients with heart failure with preserved ejection fraction (HFpEF) and combined post- and pre-capillary pulmonary hypertension (Cpc-PH)

Pulmonary hypertension due to left heart disease: analysis of survival according to the haemodynamic classification of the 2015 ESC/ERS guidelines and insights for future changes.

Pulmonary hypertension (PH) is a relevant complication of left heart disease (LHD). The 2015 ESC/ERS PH guidelines report two different haemodynamic subsets of PH due to LHD (PH-LHD) based on levels of pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG): isolated post-capillary PH (Ipc-PH) and combined post- and pre-capillary PH (Cpc-PH). The objective of this study is to evaluate the prognostic value of Ipc-PH and Cpc-PH. Data from 276 consecutive incident patients with PH-LHD were included. According to the guidelines, Ipc-PH is defined by DPG <7 mmHg and/or PVR ≤3 Wood units (WU) and Cpc-PH by DPG ≥7 mmHg and/or PVR >3 WU. Using this definition, we identified three patient groups: Ipc-PH with both normal PVR and DPG (108 patients); Cpc-PH with both increased PVR and DPG (66 patients); and an intermediate group with either increased PVR or DPG (102 patients). Survival was estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Patients with Ipc-PH had better survival compared with the group of patients with Cpc-PH (P = 0.026) and the intermediate group (P = 0.025). No survival difference was detected between patients with Cpc-PH and the intermediate group (P = 0.891). Patients with normal PVR had a better survival compared with those with elevated PVR (P = 0.012); while no difference was observed according to the level of DPG (P = 0.253). Patients with Ipc-PH have a better prognosis compared with patients with Cpc-PH and with patients with isolated increase of PVR or DPG. Pulmonary vascular resistance has a better predictive value than DPG in patients with PH-LHD.

Abstract 11257: Physiologic Quantification of the Diastolic Pressure Difference Re-classifies Pulmonary Hypertension in Patients With Advanced Heart Failure

Introduction: Assessment of pulmonary hypertension (PH) by right heart catheterization remains important in the evaluation of advanced heart failure (HF) patients being considered for cardiac transplant. Delineating ‘isolated’ post-capillary PH (Ipc-PH) and ‘combined’ pre- and post-capillary PH (Cpc-PH) remains a challenge in hemodynamic assessment, as the usual practice of calculating the diastolic pressure difference (DPD) has limitations pre-disposing it to underestimation. Hypothesis: QRS-gated calculation of the DPD (QRS-DPD), specific to late diastole when the DPD is expected to be small, will reduce the frequency of negative DPD values, and re-classify a subset of patients as Cpc-PH. Methods: Advanced HF patients (n = 136, median age = 56 years) referred for right heart catheterization within the clinical evaluation for cardiac transplant candidacy were studied. Hemodynamics were analyzed offline and measurements were averaged over 8-10 beat intervals. Automated measurements of systolic/diastolic/mean pulmonary artery pressure (sPAP/dPAP/mPAP), and mean pulmonary artery wedge pressure (mPAWP) were generated as per usual practice. Usual practice DPD (UP-DPD) was calculated as [dPAP – mPAWP]. Within the same intervals, pulmonary artery pressure (QRS-PAP) and pulmonary artery wedge pressure (QRS-PAWP) gated to the QRS-onset were manually measured for each beat and averaged. QRS-DPD was calculated as [QRS-PAP – QRS-PAWP]. Results: The mean UP-DPD was 0 ± 5 mmHg, and was &lt;0 mmHg in 61/136 cases (45%). The mean QRS-DPD was 5 ± 4 mmHg, and was &lt;0 mmHg in 10/136 cases (7%) (p &lt; 0.05). Of 136 cases, 67 (49%) demonstrated mPAP ≥25 mmHg and mPAWP &gt;15 mmHg. Using the UP-DPD classified 4/67 as Cpc-PH (DPD ≥7 mmHg), while the QRS-DPD classified 22/67 as Cpc-PH (p &lt; 0.05). Conclusions: QRS-gated measurements increase the calculated DPD, and reduce the frequency of negative values. In advanced HF patients with PH, up to 25% of Ipc-PH cases may be re-classified as Cpc-PH.