Severe Precapillary Pulmonary Hypertension Research Articles

Retrospective evaluation of a right heart parameter score in the assessment of precapillary pulmonary hypertension in dogs (2017-2021): 135 cases.

To determine if emergency and critical care residents can identify moderate to severe precapillary pulmonary hypertension on cardiologist-obtained cineloops using a pulmonary hypertension score (PHS) and report the interobserver variability of the PHS. Multicenter, retrospective, case-control study from 2017 to 2021. Private referral center and veterinary teaching hospital. One hundred and thirty-five client-owned dogs that underwent diagnostic echocardiography. None. Medical records of dogs with stage B1 myxomatous mitral valve disease (MMVD) and dogs diagnosed with precapillary pulmonary hypertension (PCPH) via echocardiograms were reviewed. Dogs were categorized by a cardiologist into 5 groups (normal, B1 MMVD, mild, moderate, and severe PCPH) based on Doppler pulmonary pressure gradients and right heart morphology. Cineloops from each case were subjectively evaluated by emergency and critical care residents for the presence of right atrial and ventricular enlargement, right ventricular hypertrophy, interventricular septal flattening, and pulmonary artery and trunk enlargement to form a composite pulmonary hypertension score out of 8 (PHS8). When available, signs of peritoneal effusion and distention of the caudal vena cava were subjectively assessed to generate a pulmonary hypertension score out of 10 (PHS10). There was excellent discrimination of moderate to severe PCPH versus grouped absent to mild PCPH using PHS8 (area under the receiver operator curve [AUC] [95% confidence interval, CI]=0.90 [0.84-0.95], P<0.0001) and PHS10 (AUC [95% CI]=0.89 [0.81-0.97], P<0.0001). PHS8≥3 was 64% sensitive and 98% specific for moderate to severe PCPH (positive likelihood ratio [LR+] 32, negative likelihood ration [LR-] 0.37). PHS10≥3.3 was 64% sensitive and 92% specific for moderate to severe PCPH (LR+ 8, LR- 0.39). Interobserver agreement was good to excellent (intraclass correlation coefficient [ICC]=0.74 [95% CI: 0.66-0.80], n=135). Residents identified moderate to severe PCPH in dogs using PHS on cineloops previously obtained by a cardiologist. The interrater agreement was good to excellent with limited training. Prospective studies to determine if residents can obtain diagnostic images for PHS are warranted.

Transient severe precapillary pulmonary hypertension caused by eosinophilic granulomatosis with polyangiitis in a patient diagnosed with asthma.

Transient severe precapillary pulmonary hypertension caused by eosinophilic granulomatosis with polyangiitis in a patient diagnosed with asthma.

A CASE OF PULMONARY HYPERTENSION ASSOCIATED WITH MYELOFIBROSIS: THERAPEUTICAL CHALLENGES FROM ACUTE TO CHRONIC SETTING

Abstract A 85–year–old female was transferred to our ICCU for acute heart failure from one of our spoke hospitals. The patient had a long history of chronic myelofibrosis, treated with fedratinib as a second–line agent after ruxolitinib failure. During a recent hospital admission, transthoracic echocardiography already showed signs of severe pulmonary hypertension (PH) with right ventricular (RV) dysfunction, so diuretic was started. On admission the patient presented showed consistent with acute on chronic kidney injury (serum Cr 3.2 mg/dl), stable anemia (Hb 9.2 mg/dl) and markedly elevated Nt–proBNP. A pulmonary CT–scan excluded acute pulmonary embolism and lung parenchymal alterations, with a clear dilation of main pulmonary artery. Transthoracic echocardiography (figure 1) confirmed precapillary PH phenotype diagnosis. Electrocardiogram (figure 2) showed sinus rhythm; incomplete RBBB, T wave inversion in V2 to V4. The patient was initially treated with high dose furosemide, low flow oxygen; but later she needed multiple cycles of inotropes, vasopressors and combined diuretic therapy (metolazone and acetazolamide) to stabilize the clinical setting. The patient also experienced episodes of paroxysmal high ventricular rate atrial flutter. After resolution of volume overload, a right heart catheterization was performed and findings were consistent with severe precapillary pulmonary hypertension: PA pressure 90/58/40 mmHg, normal PCWP, high PVR, mild cardiac index reduction. Due to critical clinical situation, Sildenafil 20 mg was started as an off–label therapy for PH (group 5). Subsequently, the patient experienced gradual but constant hemodynamic and clinical improvement and was discharged in NYHA class II. At 1 month control, patient was stable, echocardiogram revealed improvement in right ventricle dimension, systolic function and right atrial enlargement. At three months, patient is still in an intermediate risk class for PH, so we are evaluating a combination therapy (either endothelin receptor antagonist or prostanoids), taking into account anemia and thrombocytopenia. Take home message: PH can be a complication of hematological disorders as myelofibrosis, included in “mixed” forms (group 5) of PH. In our patient, after a challenging management for acute right heart failure, an off–label PDE–5 inhibitor stabilized the clinical scenario: more data are needed on PH drugs use in this setting where up to now therapeutic strategies are lacking.

Characteristics and outcomes of gemcitabine-associated pulmonary hypertension.

Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear. The objective of the present study was to assess the association between gemcitabine and PH. We identified incident cases of precapillary PH confirmed by right heart catheterisation in patients treated with gemcitabine from the French PH Registry between January 2007 and December 2022. The aetiology, clinical, functional, radiological and haemodynamic characteristics of PH were reviewed at baseline and during follow-up. A pharmacovigilance disproportionality analysis was conducted using the World Health Organization (WHO) pharmacovigilance database. We identified nine cases of pulmonary arterial hypertension, either induced (in eight patients) or exacerbated (in one patient) by gemcitabine. Patients exhibited severe precapillary PH, with a median mean pulmonary arterial pressure of 40 (range 26-47) mmHg, a cardiac index of 2.4 (1.6-3.9) L·min-1·m-2 and a pulmonary vascular resistance of 6.3 (3.1-12.6) Wood units. The median time from the initiation of gemcitabine to the onset of PH was 7 (4-50) months, with patients receiving a median of 16 (6-24) gemcitabine injections. Six patients showed clinical improvement upon discontinuation of gemcitabine. In the WHO pharmacovigilance database, we identified a significant signal with 109 cases reporting at least one adverse event related to PH with gemcitabine. Both clinical cases and pharmacovigilance data substantiate a significant association between gemcitabine use and the onset or worsening of precapillary PH. The observed improvement following the discontinuation of treatment underscores the importance of PH screening in gemcitabine-exposed patients experiencing unexplained dyspnoea.

Survival and response to pulmonary vasodilator therapies in patients with chronic obstructive pulmonary disease and pulmonary vascular phenotype

BackgroundThe aim of the study was to describe and investigate the effect of pulmonary arterial hypertension (PAH) therapies in a cohort of patients with severe precapillary pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD), and to assess factors predictive of treatment response and mortality. Material and methodsWe retrospectively included patients with severe incident PH-COPD who received PAH therapy and underwent RHC at diagnosis and on treatment. ResultsFrom 2015 to 2022, 35 severe PH-COPD patients, with clinical features of pulmonary vascular phenotype, were included. Seventeen (48.5%) patients were treated with combined PAH therapy. PAH therapy led to a significant improvement in hemodynamics (PVR -3.5 Wood Units (−39.3%); p < 0.0001), and in the simplified four-strata risk-assessment score, which improved by at least one category in 21 (60%) patients. This effect was more pronounced in patients on dual therapy. Kaplan-Meier estimated survival rates at 1, 3 and 5 years were 94%, 65% and 42% respectively. Univariate analysis showed a significant reduction in survival in patients with a higher simplified risk score at follow-up (Hazard ratio (HR) 2.88 [1.16–7.15]; p = 0.02). Hypoxemia <50 mmHg was correlated to mortality in multivariate analysis (HR 4.33 [1.08–17.42]; p = 0.04). ConclusionsOur study confirms the poor prognosis of patients with COPD and a pulmonary vascular phenotype and the potential interest of combined PAH therapy in this population, with good tolerability and greater clinical and hemodynamic improvement than monotherapy. Using the simplified risk score during follow-up could be of interest in this population.

Elevated pulmonary vascular resistance is associated with increased lung transplant waitlist mortality among patients with chronic obstructive pulmonary disease and pulmonary hypertension: a retrospective cohort analysis

BackgroundThe latest European Society of Cardiology and European Respiratory Society guidelines have changed the definition of both pre-capillary pulmonary hypertension (PH) and severe PH in chronic lung disease. The clinical significance of these new criteria are unclear among patients with chronic obstructive pulmonary disease (COPD)-PH. We aim to examine the clinical significance of the new PH definitions with regards to lung transplant waitlist mortality amongst patients with COPD-PH.MethodsThis was a retrospective cohort study of adult patients with COPD-PH listed for lung transplantation. Kaplan–Meier survival analyses were performed comparing patients with newly defined pre-capillary PH to those without pre-capillary PH and comparing patients with severe PH, defined as pulmonary vascular resistance (PVR) > 5 WU, to those without severe PH. Both mean pulmonary artery pressure (mPAP) and PVR were analyzed for potential cut-off points associated with increased waitlist mortality. Predictors of waitlist mortality were identified via Cox regression.ResultsAmong 6495 patients with COPD-PH listed for lung transplantation, pre-capillary PH was not associated with increased waitlist mortality (logrank p = 0.43), while severe PH was (logrank p < 0.001). Both severe PH (HR 1.79, 95% CI 1.22–2.60, p = 0.003) and PVR > 3.9 WU (HR 1.49, 95% CI 1.14–1.95, p = 0.004) were independently and significantly associated with increased waitlist mortality.ConclusionsPVR may serve as a strong predictor of lung transplant waitlist mortality among patients with COPD-PH as compared to other pulmonary hemodynamic parameters when predicting transplant waitlist mortality.

Intravenous Diuresis in Severe Precapillary Pulmonary-Hypertension-Related Right Heart Failure: Effects on Renal Function and Blood Pressure.

In patients with right heart failure (RHF) and pulmonary hypertension (PH), classical teaching often advises cautious diuresis in the setting of 'preload dependence' to avoid renal injury and hemodynamic compromise. However, while this physiology may hold true in some clinical settings, such as acute ischemia with right ventricular infarction, it cannot necessarily be extended to PH-related RHF. Rather, in patients with precapillary PH and decompensated RHF, diuresis aimed to decongest the right heart and systemic venous system may be directly beneficial. This study aimed to evaluate the effects of diuresis on renal function and blood pressure in patients with severe precapillary PH. A retrospective chart review was conducted on 62 patients with severe precapillary PH admitted for decompensated RHF. The hemodynamic phenotype of these patients was characterized by invasive hemodynamics and echocardiographic data. Laboratory and hemodynamic data were collected at both admission and discharge. After large-volume diuresis in this patient population, there was an improvement in both glomerular filtration rate and creatinine. While there was a decline in blood pressure after diuresis, this was not clinically significant, given the blood pressure remained in a normal range with improvement in renal function. In conclusion, this study demonstrated that despite concern for preload dependence, significant diuresis in patients with acute decompensated RHF from precapillary PH is not only safe but beneficial.

Reconsidering the limited role of right heart catheterization on severe pulmonary hypertension-due to progressive interstitial lung disease in young male patient : a case report

Pulmonary hypertension (PH)-associated with interstitial lung disease (ILD) develops as a consequence of progressive underlying lung disease or disproportionately to the underlying disease. The PH investigation by right heart catheterization (RHC) for defining PH severity is recommended in patients with ILD who show more severe symptoms than expected from lung disease, appearance of right heart failure, and clinical deterioration not matched by the declining lung function. In patient with progressive ILD, RHC is only considered if it affects the future treatment such as lung transplantation or enrollment in clinical trial/registry. The decision to undertake the RHC in progressive ILD was still fraught with doubts. Here we reported a young adult male patient with ILD whom developed progressive signs and symptoms. By RHC, he had severe precapillary PH with hemodynamic parameters indicated the presence of pulmonary vascular disease. A PH-specific treatment, sildenafil citrate, was administered, and patient responded well and was clinically stable during the addition of sildenafil citrate. This case highlights the clinical implication of performing RHC in progressive ILD, which can change the treatment decision by PH-specific drugs. Therefore, the RHC decision making in patient with progressive ILD need reconsideration.

Prognostic Value of Respiratory Variation in Right Atrial Pressure in Patients With Precapillary Pulmonary Hypertension

Precapillary pulmonary hypertension (PH) is characterized by elevated mean pulmonary artery pressure from increased pulmonary vascular resistance (PVR). Lack of respiratory variation in right atrial pressure (RAP) can be viewed as a surrogate for severe PH and inability of the right ventricle (RV) to tolerate preload augmentation during inspiration. Is the lack of respiratory variation in RAP predictive of RV dysfunction and worse clinical outcomes in precapillary PH? We retrospectively reviewed RAP tracings of patients with precapillary PH who underwent right heart catheterization. Patients with respiratory variation in RAP (end expiratory - end inspiratory) ≤2 mmHg were considered to have effectively no meaningful variation in RAP. Lack of respiratory variation in RAP was associated with lower cardiac index by indirect Fick (2.34±0.09 vs. 2.76±0.1 L/min/m2, p=0.001), lower pulmonary artery saturation (60±1.02% vs 64±1.15%, p=0.007), higher PVR (8.9±0.44 vs 6.1±0.49 Wood units, p<0.0001), RV dysfunction on echocardiography (87.3% vs 38.8%, p<0.0001), higher proBNP (2163±2997 vs 633±402 ng/ml, p<0.0001), and more hospitalizations within 1 year for RV failure (65.4% vs 29.6%, p<0.0001). There was also a trend toward higher mortality at 1 year in patients with no respiratory variation in RAP (25.4% vs 11.1%, p=0.06). Lack of respiratory variation in RAP is associated with poor clinical outcomes, adverse hemodynamic parameters, and RV dysfunction in patients with precapillary PH. Larger studies are needed to further evaluate its utility in prognosis and potential risk stratification in patients with precapillary PH.

Echocardiographic Assessment of the Pulmonary Vein to Pulmonary Artery Ratio in Canine Heartworm Disease.

A total of 151 naturally heartworm-infected and 66 healthy dogs were included in the study. The presence/absence of PH was based on the right pulmonary artery distensibility index (RPAD index < 29.5%), and the PV:PA ratio was echocardiographically measured by the time-motion mode (M mode) and two-dimensional mode (2D mode). Other echocardiographic parameters were also assessed (pulmonary trunk to aorta ratio, tricuspid regurgitation pressure gradient, and AT:ET ratio). The results of the PV:PA ratio showed a highly positive correlation between the M and 2D modes (r = 0.928). The PV:PA ratio obtained by the M mode was identified as the strongest predictor for RPAD index (R2 0.628, p < 0.0001) with a good diagnostic accuracy (AUC = 0.99). The results of PV/PA by the 2D mode showed a similar prediction for the RPAD index (R2 0.606, p < 0.0001) with a good diagnostic accuracy (AUC = 0.98). Both of the 2D and M modes' PV:PA ratios decreased significantly with the presence of PH. A cut-off value of ≤0.845 showed high sensitivity and specificity for the M mode (97% and 94%, respectively) and the 2D mode (96% and 93%, respectively). The PV:PA ratio may be useful as a complementary diagnostic method for the estimation of moderate or severe PH in dogs with heartworm.

733 NT-PROBNP CONCENTRATIONS ACROSS PULMONARY HYPERTENSION GROUPS

Abstract Background Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are found in both pre-capillary pulmonary hypertension (PH), including pulmonary arterial hypertension, PH associated with hypoxia/lung disease and chronic thromboembolic pulmonary hypertension, and post-capillary PH associated with left heart disease. We asked the question of whether NT-proBNP concentrations differ among these PH subtypes. Methods Based on right heart catheterization (RHC) data collected at our institution between Jan. 2019 and Dec. 2021, 146 patients were classified as no PH, pre-capillary PH, isolated post-capillary PH (iPC-PH) or combined pre- and post-capillary PH (cPC-PH) according to the 2022 ESC/ERS guidelines (GL). NT-proBNP values were compared across PH groups by Kruskal-Wallis test with Bonferroni correction. The characteristics of subjects with pre-capillary PH and NT-proBNP ≤ or &amp;gt;1.100 pg/mL, a cut-off for severity proposed by the 2022 GL, were compared by chi-square test, T-test, or Mann-Whitney test, as appropriate. We also applied the hemodynamic definitions of the 2018 6th World Symposium on PH (6WSPH) and of the 2015 GL, examined the differences in the distribution of PH groups with the McNemar test, and reassessed NT-proBNP concentrations. Results 44 (30%) of patients did not have PH, 38 (26%) had pre-capillary PH, 18 (12%) had iPC-PH, and 46 (32%) had cPC-PH. NT-proBNP levels were progressively higher from pre-capillary PH to iPC-PH to cPC-PH (Figure). Interestingly, the 25th percentile of the cPC-PH group was 1.138 pg/mL, close to the 1.100 pg/mL cut-off. Compared with patients with pre-capillary PH and NT-proBNP ≤1.100 pg/mL, those with &amp;gt;1.100 pg/mL NT-proBNP had larger right ventricle basal diameter [50 (43-53) vs 43 (36-45) mm; p=0.02], lower TAPSE/sPAP ratio [0.21 (0.15-0.25) vs 0.35 (0.25-0.43), p=0.01], more often massive tricuspid regurgitation (83% vs 20%, p&amp;lt;0.001), higher pulmonary vascular resistance [9.5 (7.6-15.1) vs 5.7 (2.7-7.8) WU; p=0.004], and lower stroke volume index [28 (17-32) vs 36 (32-50) mL/m2; p=0.002]. The proportion of no PH decreased and the one of cPC-PH increased when the 6WSPH or the 2015 GL criteria were used (p for trend &amp;lt;0.001). Nonetheless, the trend of NT-proBNP remained similar to that observed with the 2022 GL definitions (Figure). Conclusions A gradient of NT-proBNP exists across PH groups, with the highest values being in cPC-PH. The concentrations of NT-proBNP in severe pre-capillary PH overlap with those in cPC-PH, indirectly confirming the validity of this biomarker to discriminate the severity of pre-capillary PH.

Abstract 9729: Pulling Out All the Stops (for a Diagnosis): A Case of Progressive Dyspnea

A 63-year-old woman with hypertension, diabetes mellitus, severe obesity, obstructive sleep apnea, and history of GATA3+/ER+ breast cancer treated 14 years prior with neoadjuvant anthracycline-based chemotherapy and subsequent lumpectomy, chest radiotherapy, and letrozole presented to the emergency department with three weeks of progressive cough and exertional dyspnea. Physical examination revealed tachypnea, hypoxemia, a prominent P2, and jugular venous distension with a Kussmaul sign. Further investigation showed moderate hemolytic anemia, severe thrombocytopenia, and elevated natriuretic peptides. Electrocardiography revealed normal sinus rhythm, an S1Q3T3 pattern, and diffuse T wave inversions. Computed tomography angiography of the chest was notable for few small pulmonary nodules and diffuse vertebral osteosclerosis, consistent with osteoblastic metastases. Transthoracic echocardiography exhibited a moderately dilated RV with moderate systolic dysfunction, moderate TR, and an estimated RVSP of 79 mm Hg. Lung perfusion scintigraphy disclosed subtle subsegmental defects. Right heart catheterization (RHC) showed elevated right-sided filling pressures and severe precapillary pulmonary hypertension (RA 12 mm Hg, mPAP 51 mm Hg, PCWP 6 mm Hg, and PVR 775 dynes-sec/cm 5 ). There was no discernable shunt. These findings, coupled with the patient’s history, rapidly progressive symptoms, and hematologic derangements, raised suspicion for pulmonary tumor thrombotic microangiopathy (PTTM). A pulmonary capillary wedge blood aspirate was sent for cytology. Her clinical status rapidly worsened despite inhaled pulmonary vasodilators, hemodynamic support, and systemic glucocorticoids, precluding candidacy for empirical chemotherapy. She was transitioned to comfort measures only and suffered a bradycardic PEA arrest on hospital day 8. Autopsy was declined. Cytological analysis of the wedge blood aspirate ultimately revealed clusters of neoplastic GATA3+ cells, consistent with PTTM associated with late recurrence of breast carcinoma. This case highlights the rare instance of PTTM diagnosis aided by wedge cytology, reinforcing the multidimensional role of RHC in this extremely uncommon and devastating clinical entity.

Evaluation of Pulmonary Hypertension in Dogs with Heartworm Disease Using the Computed Tomographic Pulmonary Trunk to Aorta Diameter Ratio.

Simple SummaryPulmonary hypertension (PH) is a consequence of proliferative pulmonary endoarteritis caused by the parasite Dirofilaria immitis (heartworm). To date, the diagnosis is carried out through echocardiographic determinations, with the right pulmonary artery distensibility (RPAD) index being the gold standard for diagnosis of PH caused by heartworm. Given the high importance and frequency of PH in dogs, the study of the pulmonary trunk to aorta ratio (PT:Ao) determined by computed tomography (CT) was proposed to assess its usefulness in the diagnosis of PH, compared to the gold standard method. The results show that the PT:Ao ratio was reliable for detecting and staging the severity of moderate to severe PH in dogs with heartworm.Dirofilaria immitis causes proliferative pulmonary endoarteritis that leads to the appearance of chronic precapillary pulmonary hypertension (PH) in dogs. Pulmonary trunk to aorta ratio (PT:Ao ratio) obtained by computed tomography (CT) was studied and the quantitative measure of the diameters of the pulmonary trunk (PT), the descending thoracic aorta (DAo) and ascending thoracic aorta (AAo) were evaluated for the determination of the presence of moderate to severe PH in 59 dogs. The diagnosis of PH was echocardiographically determined, based on the determination of the right pulmonary artery distensibility (RPAD) index (<29.5%), and compared with other parameters for estimating PH. The results showed a very high concordance: 0.976 (p-value 0.000) between the two CT methods (PT:DAo and PT:AAo) with an excellent intraclass correlation coefficient > 0.95. Moreover, cut-off values of ≥1.111 for PT:DAo, and ≥1.057 for PT:AAo were determined for dogs with an RPAD index < 29.5%, which suggests a cut-off value between healthy dogs and the presence of PH. As has been previously published, The PT:Ao ratios did not determine the presence of mild PH, so the measurements cannot be considered useful for the early diagnosis of PH in dogs with heartworm.

Clinical Characteristics of Patients Undergoing Right Heart Catheterizations in Community Hospitals.

BackgroundRecognition of precapillary pulmonary hypertension (PH) has significant implications for patient management. However, the low a priori chance to find this rare condition in community hospitals may create a barrier against performing a right heart catheterization (RHC). This could result in misclassification of PH and delayed diagnosis/treatment of precapillary PH. Therefore, we investigated patient characteristics and echocardiographic parameters associated with the decision whether to perform an RHC in patients with incident PH in 12 Dutch community hospitals.Methods and ResultsIn total, 275 patients were included from the OPTICS (Optimizing PH Diagnostic Network in Community Hospitals) registry, a prospective cohort study with patients with incident PH; 157 patients were diagnosed with RHC (34 chronic thromboembolic PH, 38 pulmonary arterial hypertension, 81 postcapillary PH, 4 miscellaneous PH), while 118 patients were labeled as probable postcapillary PH without hemodynamic confirmation. Multivariable analysis showed that older age (>60 years), left ventricular diastolic dysfunction grade 2–3, left atrial dilatation were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension‐associated conditions, right atrial dilatation, and tricuspid regurgitation velocity ≥3.7 m/s favor an RHC performance.ConclusionsOlder age and echocardiographic parameters of left heart disease were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension‐associated conditions, right atrial dilation, and severe PH on echocardiography favored an RHC performance. As such, especially elderly patients may be at an increased risk of diagnostic delays and missed diagnoses of treatable precapillary PH, which could lead to a worse prognosis.

P392 A MULTIMODALITY IMAGING DIAGNOSIS OF A CHALLENGING CASE OF CONCOMITANT GROUP 1 PULMONARY HYPERTENSION AND PARADOXICALLY LOW–FLOW, LOW–GRADIENT AORTIC STENOSIS

Abstract A 76 year old woman was admitted to our hospital for self–limiting dyspnoea (NYHA class III) in oxygen dependence and frequent lipothymia following Valsalva manoeuvres. She was previously admitted to a Spoke Centre for heart failure (HF) with preserved ejection fraction (EF) and a new diagnosis of “pre–capillary pulmonary hypertension (PH)”. Despite a diagnosis of PH of unclear aetiology, she was started on macitentan without being reassessed for functional capacity due to Covid emergency; because of worsening symptoms, she was admitted to our Hub Centre. Resting ECG showed right axis deviation, right ventricle (RV) hypertrophy, first–degree atrioventricular block and right bundle branch block. Transthoracic echocardiography (TTE) showed reduced left ventricular (LV) volume with preserved EF (diastolic volume= 37 ml, EF = 88%), severe right atrial and RV dilation with flattening of the interventricular septum, estimated pulmonary artery systolic pressure (PASP) of 124 mmHg, and moderate calcific aortic stenosis (peak aortic velocity 3.3 m/s, mean gradient 25 mmHg, valve area 1.1 cm2). Right and left heart catheterization showed severe pre–capillary PH (mean pulmonary pressure 60 mmHg, mean wedge 11 mmHg, pulmonary vascular resistance 14.41 WU), a severe aortic valve stenosis (aortic valve area 0.68 cmq and peak–to–peak gradient 25 mmHg, slight reduction of cardiac index 2.04 l/min/mq) and no significant coronary artery disease. The degree of aortic stenosis was considered as moderate–severe by integrating data of transesophageal echocardiography (planimetric area 1cm2) and assessment of calcium score (1615 Agatson units). Pneumological causes, chronic thromboembolic PH, rheumatologic diseases, HIV infection, paraneoplastic origin and veno–occlusive disease were all ruled out as potential PH causes and a diagnosis of Idiopathic pulmonary arterial hypertension (IPAH) was finally made. The Heart Team established the best therapeutic option was a transcatheter aortic valve replacement (TAVI) allowing better haemodynamic tolerability of PH therapy. The patient underwent TAVI and was started on PH therapy; a complete atrio–ventricular block developed after the procedure, requiring permanent pacemaker (PM) implantation. Unfortunately, few days later, the patient died following pacemaker’s lead dislocation. Conclusion PH has a diverse aetiology, and prognosis is generally poor, especially in patients with severe comorbidities.

P427 LATE TREATMENT OF A CASE OF PULMONARY ARTERY HYPOPLASIA

Abstract Here we want to present the case of a woman who came to our observation for the onset of dyspnea due to exertion. It is a subject followed from a young age for a congenital malformation of the urinary tract. At that time the presence of stenosis of the branches of the pulmonary artery associated with an interventricular septal defect was accidentally diagnosed; however the blood pressure values in the pulmonary artery were within the limits, so no interventional therapy was undertaken. In the following years the patient developed systemic arterial hypertension associated with renal failure for which medical therapy was started and an annual follow–up was scheduled. Over the years various echocardiographic checks were repeated without ever finding high pressures in the pulmonary artery. At the last check, performed precisely for the onset of dyspnea from exertion, the estimated systolic pressure in the pulmonary artery was equal to 100 associated with a dilation of the right ventricle with hypertrophy, hepatomegaly was also present in the absence, however, of signs of peripheral congestion. The catheterization of the right heart confirmed the presence of severe precapillary pulmonary hypertension and the CT scan with three–dimensional reconstruction highlighted the almost total agenesis of the left lung branch thus revealing the presence of a pulmonary hypertension of the fourth group, also supported by the negativity of the other tests proposed in the diagnostic work of the ESC Guidelines. In agreement with a national reference center for the treatment of pulmonary hypertension, we started Bosentan therapy with increasing dosage up to the target dose and long–term oxygen therapy. After four months of follow–up, the patient shows an improvement in functional capacity and the haemodynamic data remain stable. To our knowledge there are only the experiences of single centers regarding the treatment of forms of pulmonary hypertension due to anatomical malformations of the pulmonary circulation and for this reason medical therapy is not standardized. This subset of patients represents a challenge for the clinician as hypertension can be secondary both to the lack of part of the vascular bed and to reactive hyperplasia of the endothelium of the remaining circulation due to parietal stress due to pressure overload.

The association between sleep-related breathing disorders and pre-capillary pulmonary hypertension: A chicken and egg question

The level of knowledge about a direct link between sleep-related breathing disorders and pre-capillary pulmonary hypertension (PH) is low and there is a chicken and egg question to know which disease causes the other. On one hand, sleep-related breathing disorders are considered as a cause of group 3 PH, in the subgroup of patients with hypoxemia without lung disease. Indeed, isolated sleep-related breathing disorders can lead to mild pre-capillary PH on their own, although this is rare for obstructive sleep apnea and difficult to establish for obesity-hypoventilation syndrome, the evolution towards PH being observed especially in the presence of respiratory comorbidities. The hemodynamic improvement under treatment with continuous positive airway pressure or non-invasive ventilation also argues for a causal link between pre-capillary PH and sleep-related breathing disorders. On the other hand, patients followed for pre-capillary PH, particularly pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, develop more sleep-related breathing disorders than the general population, especially sleep hypoxemia, central sleep apnea in patients with severe PH and obstructive sleep apnea in older patients with higher body mass index. The main objective of this article is therefore to answer two main questions, which will then lead us to discuss the bilateral link between these diseases: are sleep-related breathing disorders independent risk factors for pre-capillary PH and does pre-capillary PH induce sleep-related breathing disorders? In other words, who is the chicken and who is the egg?

Characteristics and Long-term Outcomes of Pulmonary Venoocclusive Disease Induced by Mitomycin C

Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) predominantly characterized by pulmonary vein and capillary involvement. An association between chemotherapy, in particular mitomycin C (MMC), and PVOD has been reported. What are the characteristics of MMC-induced PVOD, and what is the prognosis for patients with MMC-induced PVOD? We report the clinical, functional, radiologic, and hemodynamic characteristics at diagnosis and outcomes of patients with PVOD from the French PH Registry after exposure to MMC. The results are expressed as the median (minimum-maximum). From June 2011 to December 2018, 17 incident cases of MMC-induced PVOD were identified. At diagnosis, these patients had severe clinical and functional impairment, with 12 patients having a New York Heart Association (NYHA) functional class of III or IV and a 6-min walk distance of 220 (0-465) m. Right heart catheterization confirmed severe precapillary PH with a mean pulmonary artery pressure of 38 (30-52) mmHg, a cardiac index of 2.2 (1.5-4) L/(min× m2), and pulmonary vascular resistance of 8.3 (5.1-14.5) Wood units. The diffusing capacity of the lungs for carbon monoxide was markedly decreased at 31%(20%-51%) of the theoretical values associated with severe hypoxemia. MMC was withdrawn for all patients, and 14 patients received specific pulmonary arterial hypertension (PAH) therapies. Among these patients, mild but statistically insignificant improvements were observed in NYHA functional class (P= .10), 6-min walk distance (P= .09), and pulmonary vascular resistance (-4.7 Wood units; P= .052) at reassessment (median delay of 4.8months). Three patients experienced pulmonary edema requiring the cessation or reduction of PAH treatment. The median overall survival was 20months, and the 6-, 12-, and 24-month survival rates were 76%, 58%, and 18%, respectively. PVOD after MMC treatment is a rare but life-threatening complication associated with a poor prognosis despite MMC withdrawal and PAH-specific therapy.

Phenotype and Outcomes of Pulmonary Hypertension Associated with Neurofibromatosis Type 1.

Rationale: Pulmonary hypertension (PH) associated with neurofibromatosis type 1 (NF1) is a rare and largely unknown complication of NF1.Objectives: To describe characteristics and outcomes of PH-NF1.Methods: We reported the clinical, functional, radiologic, histologic, and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs, and transplant-free survival of patients with PH-NF1 from the French PH registry.Measurements and Main Results: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median (minimum-maximum) age at diagnosis of 62 (18-82) years. At diagnosis, 92% were in New York Heart Association functional class III or IV. The 6-minute-walk distance was 211 (0-460) m. Pulmonary function tests showed low DlCO (30% [12-79%]) and severe hypoxemia (PaO2 56 [38-99] mm Hg). Right heart catheterization showed severe precapillary PH with a mean pulmonary artery pressure of 45 (10) mm Hg and a pulmonary vascular resistance of 10.7 (4.2) Wood units. High-resolution computed tomography images revealed cysts (76%), ground-glass opacities (73%), emphysema (49%), and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3, and 5 years was 87%, 54%, and 42%, respectively, and four patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling.Conclusions: PH-NF1 is characterized by a female predominance, a low DlCO, and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.

Switching from Heart-Lung to Double Lung Transplantations in Patients with Pre-Capillary Pulmonary Hypertension: A Monocentric Experience

Since 2007, extra-corporeal life support (ECLS) and national priority (NP) for organ allocation allowed to switch from heart-lung transplantation (HLT) to double lung transplantation (DLT) in most of patients with precapillary pulmonary hypertension (PH). Our objective was to determine whether switching a program of transplantation for PH from HLT to DLT provided acceptable outcomes. We performed a retrospective monocentric analysis of DLT or HLT for precapillary PH between 2007 and 2016; we excluded proportioned PH in group 3 and 5 as well as Eisenmenger syndrome; patients with corrected congenital heart diseases with severe PH were included. We reported the preoperative, operative and postoperative characteristics and re-transplantation free survival up to March 2019. We performed an univariate comparison of the data between period 1 (2007 to 2011) and period 2 (2012 to 2016). Re-transplantation-free survival were compared using Log-Rank test. We performed the same analysis in the subgroup of patients transplanted with NP status. A total of 133 patients underwent 32 HLT and 101 DLT; 58 were performed during the period 1 and 75 during the period 2. The proportion of HLT decreased from 40% (period 1) to 12% (period 2) (p<0.01); whereas the proportion of transplantation in NP remained stable (60% vs. 63%, respectively, p=NS). Between the 2 periods, preoperative age, sex ratio, proportion of PH groups, hemodynamics and function were similar (all p=NS). Re-transplantation free survival was significantly increased in the period 2 (P=0.048). Among 82 patients transplanted in NP, 35 were transplanted in the period 1 and 47 in the period 2. The proportion of HLT decreased from 60% (period1) to 13% (period 2); whereas the proportions of hemodynamic compromise at transplantation (catecholamine or ECLS) were similar (71% vs. 74%, respectively, p=NS). Between the 2 periods, preoperative age, sex ratio, proportion of PH groups and hemodynamic were similar (all p=NS) in the NP subgroup; and re-transplantation free survival tended to improve in period 2 without reaching significance (p=0.068). The proportion of HLT among patients transplanted for precapillary PH was divided by more than 3 within 10 years and was associated with better re-transplantation free survival.