Post-capillary PH Research Articles

Clinical features, hemodynamics, and outcomes of pulmonary hypertension in adults with coarctation of aorta

BackgroundPulmonary hypertension (pH) and secondary right ventricle dysfunction is present in 20 % of adults with coarctation of aorta (COA) based on echocardiographic studies. There are limited data about invasive hemodynamic characterization of PH in COA. The purpose of this study was to delineate the clinical features, hemodynamics, and outcomes of PH in COA. MethodRetrospective cohort study of adults with repaired COA that underwent right heart catheterization (RHC). PH was defined as pulmonary artery (PA) mean pressure > 20 mmHg, and PH was classified as isolated precapillary PH and combined pre/postcapillary PH. ResultsOf 99 COA patients that underwent RHC, 57 (58 %) had PH. Of the patients with PH, 14 (25 %) had isolated precapillary PH while 43 (75 %) had postcapillary PH with or without precapillary disease. The correlates of PH were PA compliance (adjusted OR 0.79, 95 % CI 0.71–0.86 per 1 ml/mmHg), left atrial reservoir strain (adjusted OR 0.95, 95 % CI 0921–0.98 per 1 %), and atrial fibrillation (adjusted OR 2.18, 95 % CI 1.20–13.5). Higher PA mean pressure was associated with risk of cardiovascular events (adjusted HR 1.04, 95 % CI 1.02–1.06 per 1 mmHg) and all-cause mortality (adjusted HR 1.05, 95 % CI 1.02–1.08 per 1 mmHg). ConclusionsPH was present in over half of adults with COA referred for RHC, and one-quarter of the patients with PH presented with isolated precapillary PH suggesting an underlying PA vascular dysfunction as a contributing mechanism. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population. Clinical summaryOf 99 adults with repaired coarctation of aorta (COA) that underwent right heart catheterization, 57 % had pulmonary hypertension (pH). Of the patients with PH, 25 % had isolated precapillary PH while 75 % had combined pre/postcapillary PH. The correlates of PH were pulmonary artery (PA) compliance, left atrial reservoir strain and atrial fibrillation. PH was associated with cardiovascular events and all-cause mortality. These data suggest PA vascular dysfunction in addition to left-sided heart disease as potential etiologies for PH in this population. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population.

Exercise pulmonary hypertension in patients with systemic sclerosis based on updated guidelines

Recent European guidelines have introduced the concept of exercise pulmonary hypertension (ex-PH). However, the clinical characteristics of ex-PH in systemic sclerosis (SSc) remains unknown. We aimed to investigate the characteristics of exercise pulmonary hypertension (ex-PH) in patients with systemic sclerosis (SSc), which are unknown. We retrospectively examined 77 patients with SSc who underwent symptom-limited exercise testing using a cycle ergometer with right heart catheterization at our hospital. Nineteen patients with postcapillary PH were excluded. Fifty-eight patients (median age, 63 years; 55 women) were divided into the overt-PH (n = 18, mean pulmonary arterial pressure [PAP] > 20 mmHg and pulmonary vascular resistance > 2 Wood units at rest), ex-PH (n = 19, mean PAP/cardiac output slope > 3), and non-PH (n = 21) groups. Exercise tolerance and echocardiography results were compared among the groups. Peak oxygen consumption was high in the non-PH group, intermediate in the ex-PH group, and low in the overt-PH group (14.5 vs. 13.0 vs. 12.5 mL/kg/min, p = 0.043), and the minute ventilation/peak carbon dioxide production slope was also intermediate in the ex-PH group (32.2 vs. 32.4 vs. 43.0, p = 0.003). The tricuspid annular plane systolic excursion/systolic PAP ratio decreased from non-PH to ex-PH to overt-PH (0.73 vs. 0.69 vs. 0.55 mm/mmHg, p = 0.018). In patients with SSc, exercise PH may represent an intermediate condition between not having PH and overt PH, according to the new guidelines.

Incidence of pulmonary hypertension in COPD and its relation to inflammatory marker interleukin-1

BackgroundMany COPD patients present with severe PH defined by a pulmonary vascular resistance (PVR) > 5 WU as measured by right heart catheterization (RHC), and inflammation is thought to be contributing strongly to pulmonary vascular remodeling in COPD besides hypoxia. Interleukin-1 (IL-1) is thought to be a major cytokine that may be involved in development of PH in these patients.ObjectiveThis study aimed to identify the incidence of PH in COPD and its relation to inflammatory marker IL-1.Patients and methodsOne-hundred COPD patients underwent echocardiography and serum IL-1 analysis, and patients with high probability of PH underwent pulmonary artery catheterization using Swan-Ganz catheter.ResultsThe mean serum IL-1 level was 82 pg/ml ± 22 pg/ml (the normal IL-1 serum level is known to be 0:5 pg/mL), 51% of the participants were categorized as having a low probability of PH, 35% was intermediate, and 14% was high. RHC results were as follows: mild combined pre- and postcapillary PH was diagnosed in 14.3% of the patients. Mild precapillary PH was found in 42.9%, making it the most common type. Severe combined pre- and postcapillary PH was noted in 21.4% of the patients. Severe precapillary PH was present in 14.3%. A significant positive correlations were observed between serum IL-1 and tricuspid regurgitation velocity (TRV) (r = 0.409, P < 0.001), estimated systolic pulmonary artery pressure (ESPAP) (r = 0.508, P < 0.001), and mean pulmonary artery pressure (mPAP) (r = 0.410, P = 0.140).ConclusionSerum IL-1 is a potent predictor of a high probability of PH in COPD patients, and there was significant positive correlation between serum IL-1 and echocardiographic findings and PH probability and RHC findings in COPD patients.

Retrospective analysis of dogs and cats with a mixed form of pulmonary hypertension and suspected pulmonary capillary hemangiomatosis in comparison to animals with predomination of precapillary pulmonary hypertension

Background: Pulmonary capillary hemangiomatosis (PCH) is an idiopathic disease with the anomalous proliferation of a small capillary-like vessel in the pulmonary tissue, which can lead to a severe form of PH. There are only several cases of PCH described in veterinary literature: 27 cases in dogs and 2 cases in cats. In veterinary medicine, PH is mostly recognized as a consequence of left heart failure as a progression of the postcapillary PH to the precapillary form. PCH is mostly described as a primary disease, but resistant postcapillary PH with the high possibility of pulmonary edema raises a speculation that PCH could be a secondary malformation to the left heart disease. Aim: Discover the features associated with the shift between left- and right-sided heart disease in the context of PH development Methods: Retrospective analysis of materials from cats and dogs with histological markers of PCH (sPCH) versus those with right heart failure (RHF). Results: Animals with histological and immunohistochemistry markers of PCH had previous history of disease with the left heart volume overload. There were no differences between the groups in radiography and gross pathology. Histologically, pulmonary fibrosis and arteriopathy could be found in RHF; in sPCH – a duplication of capillaries in alveolar septa and bizarre proliferation in surroundings structures. Conclusion: PCH could be a secondary pattern of vascular remodeling due to volume overload

Hemodynamic response to inhaled nitric oxide in patients with pulmonary hypertension and chronic kidney disease: A retrospective cohort study.

Pulmonary hypertension (PH) associated with chronic kidney disease (CKD) (PH-CKD) affects approximately 20%-40% of CKD patients and is associated with increased morbidity and mortality. PH and CKD are both pathophysiologically associated with nitric oxide (NO) deficiency. The NO pathway, an important therapeutic domain in pulmonary arterial hypertension (PAH), is an intriguing but unexplored target in PH-CKD. We sought to improve understanding of the clinical significance of the NO pathway in patients with PH-CKD by assessing the hemodynamic response to inhaled NO (iNO) during right heart catheterization (RHC). In this retrospective cohort study, patients with diagnosis codes of PH and stage IV/V CKD or end-stage renal disease and estimated glomerular filtration rate < 60 mL/min/body surface areawho underwent RHC and hemodynamic drug study between July 2011 and June 2021 were eligible. Patients with mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary vascular resistance (PVR) > 3Wood unitswere included. The final cohort included 37 patients (45.9% female, mean age 72.5 ± 9.7 years). A total of 56.7%of the cohort (21/37) had precapillary PH, while 43.2% (16/37) had combined precapillary postcapillary PH (Cpc-PH). Median survival was 3.1 years after RHC. iNO was associated with a significant decrease in both mPAP and PVR. Hemodynamic changes in mPAP and PVR were similar in precapillary and Cpc-PH groups. Among a small subset (n = 14) who were subsequently treated with PAH-targeted therapy, treatment response was mixed and did not reveal significant benefit. Further studies are warranted to better define the potential role of PAH therapy in PH-CKD.

PAH-specific treatment for patients with combined pre- and post-capillary pulmonary hypertension

Abstract Introduction Pulmonary hypertension (PH) due to left heart disease (PH-LHD) is the most frequent form of PH, constituting approximately 70% of PH patients. Depending on the extent of pressure increase in the pre-capillary bed, PH-LHD is divided into isolated post-capillary PH, where pulmonary vascular resistance (PVR) is ≤2 WU, and combined pre- and post-capillary PH (Cpc-PH), where PVR exceeds 2 WU. Compared to Ipc-PH, Cpc-PH portents substantial morbidity and poor prognosis. Current PH guidelines recommend optimal treatment of underlying pathology, with drugs approved for pulmonary arterial hypertension (PAH) being not recommended; however, therapeutic regimens specifically targeting increases in pre-capillary pressure are urgently required. Methods For this analysis, we included all patients diagnosed with Cpc-PH invluding using right heart catheterization, who presented at the PH outpatient clinic of the Medical University of Vienna, Austria, between 02/2022 and 02/2023. Cpc-PH was defined hemodynamically as an elevated mean pulmonary arterial pressure (mPAP) of &amp;gt;20 mmHg and a PVR &amp;gt;2 WU. Results A total of 30 (6.5%) patients were diagnosed with Cpc-PH. Of these, 21 (70%) were female; median age was 75 [70, 76] years. Cardiovascular risk factors were arterial hypertension in 27 (90%), diabetes mellitus in 7 (23%), hyperlipidemia in 22 (73%), atrial fibrillation in 24 (80%), chronic kidney disease in 21 (70%), and coronary artery disease in 13 (43%) patients. At diagnosis, median mPAP was 42 [36, 53] mmHg, with a PVR of 5.5 [3.4, 5.3] WU. Laboratory evidence of heart failure was illustrated by elevated NT-proBNP levels (2076 [1461, 3959] pg/mL). Transthoracic echocardiography showed mildly, moderately and severely reduced right ventricular (RV) function in 7 (23%), 9 (30%) and 3 (10%) patients. At diagnosis, 6 (20%), 20 (67%) and 4 (13%) patients were in WHO functional class II, III and IV, respectively. PAH-specific therapy was initiated in 11 (37%) patients: 7 (23%) were put on treprostinil, 4 (13%) on macitentan, 3 (10%) on riociguat, and 3 (10%) on sildenafil. In 3 (10%) patients, combination therapy was started; one (3%) patient received triple therapy. In patients in whom PAH-specific therapy was initiated, PVR at baseline was higher (6.9 [5.4, 9.9] vs. 4.9 [3.1, 5.9] WU, p=0.019). Patients on PAH-specific therapy had a higher rate of improvement in WHO-FC at follow-up (82% vs. 31%, p=0.019). Conclusions In patients suffering from Cpc-PH, PAH-specific therapy leads to improvement of symptoms. Further studies are required to extend this finding to a larger patient group to assess whether PAH-specific drugs may also improve hemodynamics, right ventricular function and mortality.

Hemodynamic characteristics in patients with pulmonary hypertension and chronic obstructive pulmonary disease: A retrospective monocentric cohort study

BackgroundPulmonary hypertension (PH) is a hemodynamic condition characterized by an abnormal elevation in pulmonary arterial pressures. Several pathophysiological pre-capillary and post-capillary mechanisms have been described. PH is a common complication of chronic obstructive pulmonary disease (COPD), however, the prevalence of each mechanism in the development of PH in patients with COPD has been hardly studied. MethodsWe reported the clinical, functional, hemodynamic characteristics and outcomes of patients diagnosed with COPD and PH among the expert PH center of Nancy between January 1st, 2015 and March 31st, 2021. Results123 patients with COPD and PH were included. Most patients (n=122, 99%) had a pre-capillary mechanism, 9% (n=11) a post-capillary mechanism, and 1% (n=1) an unclassified mechanism. 111 (90%) patients had pure pre-capillary PH and 11 (9%) patients had combined pre- and post-capillary PH. Combined pre- and post-capillary PH group was characterized by higher prevalence of cardiovascular comorbidities and of sleep apnea-hypopnea syndrome, a higher body mass index, lower lung volumes, higher mean pulmonary arterial pressure, pulmonary arterial wedge pressure and right atrial pressure. At follow-up (median 30 months), 52 patients had died, and 11 had undergone lung transplantation. One-year, three-year and five-year transplant-free survival rates were 71%, 29% and 11% respectively. There was no difference on outcomes between groups. ConclusionPH in COPD patients is mostly due to pre-capillary mechanism. However, the existence of various and numerous comorbidities in COPD, especially cardiovascular, can lead to the participation of post-capillary mechanisms in the development of PH. Further studies are needed to confirm these findings and to assess the impact on outcomes and management strategies in these different patients.

Impact of pulmonary hypertension hemodynamic presentation on perioperative outcomes in patients undergoing elective cardiac surgery: An observational study

Abstract Background Pulmonary hypertension (PH) is classified by hemodynamic presentation into precapillary, isolated postcapillary, and combined postcapillary and precapillary PH. Whether PH type influences risk stratification in cardiac surgery remains undetermined. We aimed to evaluate the incidence of perioperative (≤30 days) morbidity and mortality in different PH population. Methods This was a retrospective observational study. All patients who underwent right heart catheterization between August 2015 and July 2020 were divided into the noncapillary, precapillary, isolated postcapillary, and combined postcapillary and pre capillary PH groups based on their mean pulmonary arterial pressure, pulmonary artery wedge pressure, and diastolic pressure difference preoperatively. Results Of the 500 patients who underwent elective cardiac surgeries, 487 were analyzed. Overall, 236 patients (48.7%) had PH, and isolated postcapillary PH was the most common presentation. Mild PH proportion was highest in the precapillary PH type (70.8%), followed by isolated postcapillary PH (46.2%), and finally combined postcapillary and precapillary PH (10.7%). Patients with PH had a greater frequency of renal insufficiency and wound infection within 30 days postoperatively. Mean pulmonary arterial pressure &gt;25 mm Hg after cardiopulmonary bypass (CPB) was a risk factor for short-term complications. New York Heart Association Functional Class ≥II, long CPB duration, and isolated postcapillary PH or combined postcapillary and precapillary PH type are independent risk factors for short-term morbidity and mortality after elective cardiac surgery. Conclusions Isolated postcapillary PH and combined postcapillary and precapillary PH patients had a higher complication rate 30 days postoperatively among elective cardiac surgery patients. After CPB, mean pulmonary arterial pressure &gt;25 mm Hg was associated with greater complication frequency.

Left Heart Disease Phenotype in Elderly Patients with Pulmonary Arterial Hypertension: Insights from the Italian PATRIARCA Registry.

Pulmonary arterial hypertension (PAH) in the elderly is often associated with left heart disease (LHD), prompting concerns about the use of pulmonary vasodilators. The PATRIARCA registry enrolled ≥70 year-old PAH or chronic thromboembolic pulmonary hypertension (CTEPH) patients at 11 Italian centers from 1 December 2019 through 15 September 2022. After excluding those with CTEPH, post-capillary PH at the diagnostic right heart catheterization (RHC), and/or incomplete data, 23 (33%) of a total of 69 subjects met the criteria proposed in the AMBITION trial to suspect LHD. Diabetes [9 (39%) vs. 6 (13%), p = 0.01] and chronic kidney disease [14 (61%) vs. 12 (26%), p = 0.003] were more common, and the last RHC pulmonary artery wedge pressure [14 ± 5 vs. 10 ± 3 mmHg, p < 0.001] was higher and pulmonary vascular resistance [5.56 ± 3.31 vs. 8.30 ± 4.80, p = 0.02] was lower in LHD than non-LHD patients. However, PAH therapy was similar, with 13 (57%) and 23 (50%) subjects, respectively, taking two oral drugs. PAH medication patterns remained comparable between LHD and non-LHD patients also when the former [37, 54%] were identified by atrial fibrillation and echocardiographic features of LHD, in addition to the AMBITION criteria. In this real-world snapshot, elderly PAH patients were treated with pulmonary vasodilators, including combinations, despite a remarkable prevalence of a LHD phenotype.

Abstract 14064: Utility of Tricuspid Annular Plane Systolic Excursion Normalized by Right Ventricular Size in Pulmonary Hypertension to Predict Exercise Capacity, Pulmonary Compliance, and Clinical Outcomes

1. Introduction: While tricuspid annular plane systolic excursion (TAPSE) captures the predominant longitudinal motion of right ventricle (RV), it may not accurately predict ventricular function as the RV dilates. Hence, normalizing TAPSE to ventricular area (in systole: TAPSE/RV-area-S, and diastole: TAPSE/RV-area-D) may lead to improved assessment of right heart function. In this study, we aim to determine the utility of RV size-indexed-TAPSE metrics in predicting exercise capacity and clinical outcomes. 2. Methods: We perform a retrospective analysis of 71 consecutive subjects undergoing invasive exercise hemodynamics with cardiopulmonary exercise test for evaluation of dyspnea. Patients were classified into four groups: pulmonary arterial hypertension, isolated post-capillary, combined pre-/post-capillary PH, and control (no PH) based on hemodynamic analysis. Transthoracic echocardiogram data included: TAPSE (mm), TAPSE-index-D (RV end-diastole area in cm), and TAPSE-index-S (RV end-systole area in cm). Subjects were followed for 12 months after hemodynamic study for adverse events (death, heart failure hospitalization). 3. Results: On ROC analysis of indexed-TAPSE to predict pulmonary compliance (&gt;3.0 ml/mmHg), we identified optimal cutoff of 1.1 for TAPSE-index-D (AUC=0.792, p&lt;0.001), 1.5 for TAPSE-index-S (AUC=0.827, p&lt;0.001), and 17 mm for TAPSE (AUC=0.672, p=0.005). Similar results were obtained for predicting %predicted VO 2 max (&gt;50%). We dichotomized indexed-TAPSE based on ROC analysis. As shown in the Figure, compared to the current recommended TAPSE cut-off of 17 mm, RV size-indexed TAPSE metrics were both superior in predicting adverse outcome (p&lt;0.01). 4. Discussion/Conclusion: Normalizing TAPSE to RV size can capture longitudinal and radial motion of the RV as the ventricle dilates and have better ability to predict clinical outcomes (death and HF hospitalization).

Pulmonary vascular disease in pulmonary hypertension due to left heart disease: pathophysiologic implications.

Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in left heart disease (LHD). This study sought to characterize the pathophysiology of PVD across the spectrum of PH in LHD. Patients with PH-LHD [mean pulmonary artery (PA) pressure >20 mmHg and PA wedge pressure (PAWP) ≥15 mmHg] and controls free of PH or LHD underwent invasive haemodynamic exercise testing with simultaneous echocardiography, expired air and blood gas analysis, and lung ultrasound in a prospective study. Patients with PH-LHD were divided into isolated post-capillary PH (IpcPH) and PVD [combined post- and pre-capillary PH (CpcPH)] based upon pulmonary vascular resistance (PVR <3.0 or ≥3.0 WU). As compared with controls (n = 69) and IpcPH-LHD (n = 55), participants with CpcPH-LHD (n = 40) displayed poorer left atrial function and more severe right ventricular (RV) dysfunction at rest. With exercise, patients with CpcPH-LHD displayed similar PAWP to IpcPH-LHD, but more severe RV-PA uncoupling, greater ventricular interaction, and more severe impairments in cardiac output, O2 delivery, and peak O2 consumption. Despite higher PVR, participants with CpcPH developed more severe lung congestion compared with both IpcPH-LHD and controls, which was associated lower arterial O2 tension, reduced alveolar ventilation, decreased pulmonary O2 diffusion, and greater ventilation-perfusion mismatch. Pulmonary vascular disease in LHD is associated with a distinct pathophysiologic signature marked by greater exercise-induced lung congestion, arterial hypoxaemia, RV-PA uncoupling, ventricular interdependence, and impairment in O2 delivery, impairing aerobic capacity. Further study is required to identify novel treatments targeting the pulmonary vasculature in PH-LHD.

Pulmonary Hypertension in Rural Minnesota

<h3>Purpose</h3> Pulmonary arterial hypertension (PAH) is a progressive disease with high morbidity and mortality. The purpose of this study is to describe the prevalence and natural history of pulmonary hypertension in rural communities. <h3>Methods</h3> Retrospective review of patients with suspected PH seen at an outreach cardiology practice in rural Minnesota between 1/1/2010 and the present. Patients were ≥18 years old, with echocardiography and right heart catheterization (RHC) procedures. All patients with mean pulmonary artery pressure > 20 mmHg on RHC were included. Patients were grouped into pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (group 1), combined pre- and post-capillary PH (CPC-PH/fxoup 1*), and non-group 1 PH (groups 2, 3, and 5) using standard definitions. <h3>Results</h3> Of 272 patients, 61 patients had PAH, 48 patients had CPC-PH, and 163 patients had non-group 1 PH. Female sex was predictive of PAH (OR 2.37, 95% CI: 1.28, 4.37), as was higher RVSP on echo (OR 1.02, 95% CI: 1.01, 1.04). Moderate-severe left atrial enlargement on echo (OR 0.39, 95% CI: 0.21, 0.73), coronary artery disease (OR 0.50, 95% CI: 0.27, 0.91), and atrial fibrillation (OR 0.31, 95% CI: 0.16, 0.59) were predictive of non-group 1 PH. Patient mortality increased with age at diagnosis (<b>Figure 1</b>, p=0.002). Patient mortality was similar among group 1, CPC-PH, and non-group 1 PH. <h3>Conclusion</h3> PAH and CPC-PH patients have different baseline characteristics compared to non-group 1 PH patients yet have similar mortality. Age at diagnosis remains a critical factor in patient prognosis with higher mortality among older patients. Interestingly, males are overrepresented in this rural subset when compared to prior literature. Because rural patients often have difficulty accessing care and unique socioeconomic pressures, continued vigilant screening may result in more accurate diagnoses and improved patient morbidity and mortality.

Management of Pulmonary Hypertension Secondary to Valvular Heart Disease with Angiotensin-Receptor Neprilysin Inhibitor

<h3>Introduction</h3> Pulmonary hypertension secondary to left-sided valvular disease (VHD-PH) is associated with high morbidity and mortality. Angiotensin-receptor neprilysin inhibitor (ARNI) is a novel pharmacotherapy, which reduces afterload with natriuresis and peripheral vasodilation. Whether ARNI can also reduce pulmonary vasculature resistance is unknown. We present two cases of VHD-PH that improved after treatment with ARNI. <h3>Case Report</h3> Case 1: Ms. M is a 63-year-old woman with past medical history of rheumatic mitral valve (MV) stenosis (mean gradient = 12 mm Hg at a heart rate = 69 beats/minute) who presented with New York Heart Association (NYHA) Class IIIB symptoms. The initial workup showed normal left ventricular function (LV) but severe combined pre- and post-capillary PH (Cpc-PH). She was deemed to be a high-risk surgical candidate given the severity of PH. Subsequently, she was treated with ARNI for three months, and repeat right heart catheterization showed significant improvement in Cpc-PH (see Table). Case 2: Mr. S is a 59-year-old man with past medical history of MV endocarditis s/p remote bovine MV replacement in 1984 complicated by paravalvular leak and redo replacements who presented with worsening shortness of breath. The workup demonstrated a well-functioning MV prosthesis and normal LV function, but elevated filling pressures. After two months of diuresis, Mr. S continued to have NYHA Class IIIB symptoms with persistent Cpc-PH. He was subsequently started on ARNI, and two months later had complete resolution of his symptoms. Repeat evaluation showed normalization of pulmonary vascular resistance (PVR, see Table). <h3>Summary</h3> This report is the first to describe treatment of VHD-PH with ARNI along with invasive hemodynamic data showing successful reduction in PVR. In these two cases, treatment with ARNI led to reduction in not only mean pulmonary arterial pressures but also PVR. Future prospective trials are needed to evaluate role of ARNIs in treatment of VHD-PH.

Prognostic Power of Pulmonary Arterial Compliance Is Boosted by a Hemodynamic Unloading Test With Glyceryl Trinitrate in Heart Failure Patients With Post-capillary Pulmonary Hypertension.

BackgroundPulmonary hypertension (PH) is an established risk factor in patients with heart failure (HF). However, right heart catheterisation (RHC) and vasoreactivity testing (VRT) are not routinely recommended in these patients.MethodsThe primary objective of the present study was to explore the impact of VRT using sublingual glyceryl trinitrate (GTN) on transplant/ventricular assist device-free survival in HF patients with post-capillary PH. RHC parameters were correlated retrospectively with the primary outcome.ResultsThe cohort comprised 154 HF patients with post-capillary PH undergoing RHC with GTN-VRT at a tertiary heart failure centre. Multiple parameters were associated with survival. After adjustment for established prognosis-relevant clinical variables from the MAGGIC Score, variables with the most relevant odds ratios (OR) obtained after GTN-VRT were: calculated effective pulmonary arterial (PA) elastance (adjusted OR 2.26, 95%CI 1.30–3.92; p = 0.004), PA compliance (PAC-GTN; adjusted OR 0.45, 95%CI 0.25–0.80; p = 0.006), and total pulmonary resistance (adjusted OR 2.29, 95%CI 1.34–3.93; p = 0.003). Forest plot analysis including these three variables as well as PAC at baseline, delta PAC, and the presence of combined post- and pre-capillary PH revealed prognostic superiority of PAC-GTN, which was confirmed by Kaplan-Meier analysis.ConclusionsIn our cohort of symptomatic HF patients with post-capillary PH, improved PAC after administration of GTN was associated with survival independent of established hemodynamic and clinical risk factors. VRT using GTN may be better described as unloading test due to GTN's complex effects on the circulation. This could be used for advanced prognostication and should be investigated in further studies.

Peak oxygen uptake is a strong prognostic predictor for pulmonary hypertension due to left heart disease

BackgroundPulmonary hypertension in left heart disease (PH-LHD), which includes combined post- and precapillary PH (Cpc-PH) and isolated postcapillary PH (Ipc-PH), differs significantly in prognosis. We aimed to assess whether cardiopulmonary exercise testing (CPET) predicts the long-term survival of patients with PH-LHD.MethodsA single-center observational cohort enrolled 89 patients with PH-LHD who had undergone right heart catherization and CPET (mean pulmonary arterial pressure > 20 mm Hg and pulmonary artery wedge pressure ≥ 15 mm Hg) between 2013 and 2021. A receiver operating characteristic curve was plotted to determine the cutoff value of all-cause death. Survival was estimated using the Kaplan–Meier method and analyzed using the log-rank test. The Cox proportional hazards model was performed to determine the association between CPET and all-cause death.ResultsSeventeen patients died within a mean of 2.2 ± 1.3 years. Compared with survivors, nonsurvivors displayed a significantly worse 6-min walk distance, workload, exercise time and peak oxygen consumption (VO2)/kg with a trend of a lower oxygen uptake efficiency slope (OUES) adjusted by Bonferroni’s correction. Multivariate Cox regression revealed that the peak VO2/kg was significantly associated with all-cause death after adjusting for Cpc-PH/Ipc-PH. Compared with Cpc-PH patients with a peak VO2/kg ≥ 10.7 ml kg−1 min−1, Ipc-PH patients with a peak VO2/kg < 10.7 ml kg−1 min−1 had a worse survival (P < 0.001).ConclusionsThe peak VO2/kg is independently associated with all-cause death in patients with PH-LHD. The peak VO2/kg can also be analyzed together with Cpc-PH/Ipc-PH to better indicate the prognosis of patients with PH-LHD.

MRI Feature Tracking Strain in Pulmonary Hypertension: Utility of Combined Left Atrial Volumetric and Deformation Assessment in Distinguishing Post- From Pre-capillary Physiology.

AimsPulmonary hypertension (PH) is dichotomized into pre- and post-capillary physiology by invasive catheterization. Imaging, particularly strain assessment, may aid in classification and be helpful with ambiguous hemodynamics. We sought to define cardiac MRI (CMR) feature tracking biatrial peak reservoir and biventricular peak systolic strain in pre- and post-capillary PH and examine the performance of peak left atrial strain in distinguishing the 2 groups compared to TTE.Methods and ResultsRetrospective cross-sectional study from 1 Jan 2015 to 31 Dec 2020; 48 patients (22 pre- and 26 post-capillary) were included with contemporaneous TTE, CMR and catheterization. Mean pulmonary artery pressures were higher in the pre-capillary cohort (55 ± 14 vs. 42 ± 9 mmHg; p < 0.001) as was pulmonary vascular resistance (median 11.7 vs. 3.7 WU; p < 0.001). Post-capillary patients had significantly larger left atria (60 ± 22 vs. 25 ± 9 ml/m2; p < 0.001). There was no difference in right atrial volumes between groups (60 ± 21 vs. 61 ± 29 ml/m2; p = 0.694), however peak RA strain was lower in post-capillary PH patients (8.9 ± 5.5 vs. 18.8 ± 7.0%; p < 0.001). In the post-capillary group, there was commensurately severe peak strain impairment in both atria (LA strain 9.0 ± 5.8%, RA strain 8.9 ± 5.5%). CMR LAVi and peak LA strain had a multivariate AUC of 0.98 (95% CI 0.89–1.00; p < 0.001) for post-capillary PH diagnosis which was superior to TTE.ConclusionCMR volumetric and deformation assessment of the left atrium can highly accurately distinguish post- from pre-capillary PH.

The six-minute walk test in sarcoidosis associated pulmonary hypertension: Results from an international registry

IntroductionSarcoidosis associated pulmonary hypertension (SAPH) is a leading contributor to sarcoidosis-related mortality. The 6-min walk test (6MWT) is widely used in assessment of cardiorespiratory conditions. A reduced 6-min walk distance (6MWD) has been associated with increased mortality in SAPH. We examined patients from the Registry of Sarcoidosis Associated Pulmonary Hypertension (ReSAPH) who had performed 6MWT at enrollment to identify variables that affect 6MWD, and the prognostic value of 6MWT variables regarding death or lung transplantation. Material and methodsReSAPH patients with available 6MWT were included. Variables analyzed using pre-defined cutoffs included 6MWD, initial and end of test Borg dyspnea score, oxygen saturation, and heart rate at beginning, end, and after 1-min recovery, absolute change in oxygen saturation, modified distance-saturation product (mDSP), and the heart rate recovery at 1-min (HRR). Findings174 patients met inclusion criteria; 48 patients died and 8 underwent lung transplantation. Patients with 6MWD<300 m had a higher chance of dying or undergoing transplantation compared to those with 6MWD>300 m (p = 0.012). No associations with outcome were observed with mDSP cutoff 200 m%, desaturation≥5% and oxygen saturation<88% at end of 6MWT, or multiple HRR cutoffs (13,14,16). 6MWD correlated with initial Borg score, (p = 0.001), DLCO% (p = 0.0001) and sPAP (p = 0.031) on multivariate analysis. These variables were significant for both pre- and post-capillary PH subgroups. 6MWD also correlated with fatigue assessment scale (FAS) (p = 0.015). ConclusionOf the parameters evaluated, 6MWD had the greatest prognostic value in SAPH which correlated with other physiologic and hemodynamic variables. 6MWT captures the multidimensional effects of sarcoidosis.

肺动脉去神经术治疗肺动脉高压研究进展

交感神经过度激活在肺动脉高压(pulmonary hypertension, PH)的进展中起着重要作用。肺动脉去神经术(pulmonary artery denervation, PADN)是最近提出的利用10个电极的消融导管治疗PAH的介入方法。这篇综述介绍了肺动脉交感神经的定位，PADN的关键步骤，以及目前在第一大类肺动脉高压（pulmonary arterial hypertension, PAH）或混合型毛细管后和前性肺动脉高压 (combined pre-capillary and post-capillary PH, Cpc-PH)患者的临床试验结果。

Numerical predictions of shear stress and cyclic stretch in pulmonary hypertension due to left heart failure.

Isolated post-capillary pulmonary hypertension (Ipc-PH) occurs due to left heart failure, which contributes to 1 out of every 9 deaths in the United States. In some patients, through unknown mechanisms, Ipc-PH transitions to combined pre-/post-capillary PH (Cpc-PH) and is associated with a dramatic increase in mortality. Altered mechanical forces and subsequent biological signaling in the pulmonary vascular bed likely contribute to the transition from Ipc-PH to Cpc-PH. However, even in a healthy pulmonary circulation, the mechanical forces in the smallest vessels (the arterioles, capillary bed, and venules) have not been quantitatively defined. This study is the first to examine this question via a computational fluid dynamics model of the human pulmonary arteries, arterioles, venules, and veins. Using this model, we predict temporal and spatial dynamics of cyclic stretch and wall shear stress with healthy and diseased hemodynamics. In the normotensive case for large vessels, numerical simulations show that large arteries have higher pressure and flow than large veins, as well as more pronounced changes in area throughout the cardiac cycle. In the microvasculature, shear stress increases and cyclic stretch decreases as vessel radius decreases. When we impose an increase in left atrial pressure to simulate Ipc-PH, shear stress decreases and cyclic stretch increases as compared to the healthy case. Overall, this model predicts pressure, flow, shear stress, and cyclic stretch that providing a way to analyze and investigate hypotheses related to disease progression in the pulmonary circulation.

63 Peripheral endothelial function in patients affected by pulmonary hypertension. Relationship between endothelial function, haemodynamic parameters, and therapy response

Abstract Aims Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (mPAP) of 25 mmHg or greater at rest, confirmed by right heart catheterization (RHC). The World Health Organization has classified PH into five clinical subgroups. Pulmonary arterial hypertension (PAH) (group 1) is characterized by loss and obstructive remodelling of the pulmonary vascular bed. These patients are characterized haemodynamically by the presence of precapillary PH, defined as an mPAP of 25 mm Hg or greater, pulmonary artery wedge pressure (PAWP) of 15 mm Hg or less, and pulmonary vascular resistance (PVR) of three Wood units (WU) or greater. Pulmonary hypertension due to left-sided heart disease (LHD) (PH-LHD) (group 2) occurs in HF. Patients with PH-LHD usually have isolated postcapillary PH (PAWP &amp;gt;15 mm Hg and PVR &amp;lt;3 WU), although some of them have combined postcapillary and precapillary PH (PAWP &amp;gt;15 mm Hg and PVR ≥3 WU). PH due to chronic lung disease (CLD) (PH-CLD) and/or hypoxia (group 3) can occur in many lung diseases. These patients have precapillary PH. Chronic thromboembolic PH (CTEPH) (group 4) is characterized by obstruction of the pulmonary vasculature by organized thromboembolic material and vascular remodelling, resulting from prior pulmonary embolism. Patients with unclear and/or multifactorial mechanisms are listed as group 5. Specific pulmonary vasodilators are approved only in PAH patients. While research was predominantly focused on pulmonary vasculature, little is known about the peripheral endothelial damage in different vascular beds in PH patients. To evaluate the relationship between the peripheral endothelial function and the haemodynamic parameters, in order to provide a non-invasive method for the indirect evaluation of mean pulmonary pressure and vascular resistance, to predict if the PH is a precapillary or postcapillary, to select more accurately the patients who should undergo RHC. Moreover, we investigate if there is a possible correlation between endothelial dysfunction and response to specific PH therapies. Methods and results Patients with suspected PH, based on symptoms, medical history, and clinics will undergo physical examination, ECG, echocardiography, and RHC. In all patients, endothelial function was assessed by FMD. Medical history, heart rate, systolic blood pressure, body mass index, WHO functional class, and medications were recorded. All patients underwent blood analysis, erythrocyte sedimentation rate (ERS), high sensitivity C-reactive protein (CRP), and NT-proBNP levels were assayed. Increased peripheral endothelial dysfunction in patients with precapillary PH, with a linear correlation between endothelium dysfunction and increased PVR at the right catheterization. To differentiate pre and post capillary PH forms by cut-off values of the FMD. The degree of endothelial dysfunction could be a marker of therapy response. Sequential combination therapy in the pre-capillary PH forms could be the one with a worst endothelial response than up-front combination therapy.