Purpose: Patients with heterotaxy syndrome have a high rate of congenital heart disease, often requiring surgical interventions, including palliative procedures to augment or restrict pulmonary blood flow.Pulmonary hypertension in this setting complicates surgical interventions and overall management.Pulmonary vasodilators may be used to treat pulmonary hypertension and facilitate surgical interventions.We describe the use of pulmonary vasodilators in patients with heterotaxy syndrome.Methods: Single-center retrospective chart review of patients with heterotaxy syndrome who underwent at least one cardiac operation from Jan 1 2008 to Oct 31 2019.The diagnosis of heterotaxy syndrome was established from imaging studies performed prior to intervention.Surgical interventions were reviewed from operative reports.Pulmonary vasodilator use was assessed from progress notes and medication reconciliation at all inpatient and outpatient encounters.Results: Thirty-four patients with heterotaxy syndrome were treated at our center during the study period, with follow up ranging from 18 to 3385 days.Palliative surgical interventions included restriction of pulmonary blood flow in 8 patients and augmentation of pulmonary blood flow in 11 patients.Pulmonary vasodilators were used in 16 patients (47%): 7 (20%) received inhaled nitric oxide while admitted, 3 (9%) received supplemental oxygen as outpatients, 12 (35%) received sildenafil as outpatients, 5 (14%) received multiple agents.Treatment was initiated in the inpatient setting in all patients.All patients on supplemental oxygen and the majority of patients on sildenafil continued on treatment at most recent follow up (10 patients, 83% of patients ever prescribed).There was no difference in pulmonary vasodilator use when stratified by surgical palliation strategy, and no differences in survival between patients with and without pulmonary vasodilator use.Conclusion: Pulmonary vasodilator use is common in patients with heterotaxy syndrome undergoing surgical interventions for congenital heart disease.It is typically initiated in the inpatient setting but well-tolerated on a long-term basis, and may facilitate treatment in this challenging population.

Most pulmonary arterial hypertension (PAH) in Indonesia is associated with uncorrected congenital heart disease (CHD). Other type of PAH has not been reported from Indonesia, despite current availability of PAH-specific medication. The aim of this study is to describe the characteristics of nonCHD-associated PAH and its mortality. We had established the COHARD-PH registry which is a prospective singlecenter study enrolling adult patients with CHD-associated PAH. We also enrolled and followed subjects with nonCHD-PAH into separate cohort. Layers of diagnostic procedures were performed from echocardiography, HRCT thorax, MSCT pulmonary angiography and right heart catheterization (RHC). The baseline data were collected during the index of diagnosis of PH probability by echocardiography. The RHC was performed to diagnose PAH. Subjects were followed up during their visit to our PH clinic. Sixty-three patients were enrolled, 57 (90.5%) were idiopathic/hereditary PAH (I/H-PAH), five (7.9%) connective tissue disease-associated PAH (CTD-PAH) and one portopulmonary PAH (po-PAH). Most subjects were young females (I/H-PAH 82.5%, 39.0 14.0 years and CTDPAH 80.0%, 41.2 6.3 years). Most subjects had WHO functional class II. The RHC was performed in 26 I/H-PAH subjects, with mean mPAP 62.3 18.7mmHg and PVRi 29.2 14.0 WU. m. Most treatment was sildenafil monotherapy (71%) and sildenafilþberaprost combination (12.7%). During follow-up, 12 (19.1%) subjects died. Those who died were younger (32.6 10.8 years vs. 41.1 13.7 years, p< 0.05). Subjects with CTD-PAH had the highest mortality rate (two subjects (40%) and I/H-PAH had 15.8% mortality rate (nine subjects)). The only poPAH subject died during follow-up. Among I/H-PAH and CTD-PAH, higher right atrial diameter by echocardiography significantly associated with mortality. In I/H-PAH, mortality had tendency toward higher mPAP and PVRi. In conclusion, among non CHD-associated PAH, CTD-PAH had worse outcome as compared with I/H-PAH. Younger age and higher right atrial diameter by echocardiography were significantly associated with mortality in I/H-PAH and CTD-PAH.

Background: Clinical practice guidelines recommend screening all systemic sclerosis (SSc) patients for pulmonary arterial hypertension (PAH) with yearly echocardiograms. There is a paucity of evidence to support these guidelines. Research question: Can a prediction model identify SSc patients with a very low probability of PAH and therefore not requiring annual screening echocardiogram? Study design and methods: We performed a case-control study of 925 unselected SSc subjects nested in a multi-centered, longitudinal cohort. The probability of PAH for each subject was calculated using the results of multivariate logistic regression models. A cut-off was identified for the estimated probability of PAH below which no subject developed PAH (100% sensitivity). Results: Study subjects were predominantly female (87.5%), with mean (SD) age 58.6 (11.7) years and disease duration of 18.2 (12.2) years. Thirty-seven subjects developed PAH during 5407.97 person-years of observation (incidence rate 0.68 per 100 person-years). Shortness of breath (SOB), diffusing capacity for carbon monoxide (DLCO) and NT-proBNP were independent predictors of PAH. All SSc-PAH cases had a probability of PAH of >1.1%. Subjects below this cut-off, none of whom had PAH, accounted for 46.2% of the study population. Interpretation: A simple prediction model identified subjects at very low probability of PAH who could potentially forego annual screening echocardiogram. This represents almost half of SSc subjects in a general SSc population. This study, which is the first evidence-based study for the rational use of follow-up echocardiograms in an unselected SSc cohort, requires validation. The scoring system is freely available online at http://pahtool.ladydavis.ca. (C) 2020 Elsevier Inc. All rights reserved.

Abstract Background Pulmonary hypertension (PH) can be pre-capillary or post-capillary (PVH) etiology based on left-sided filling pressures and pulmonary vascular resistance. The 2016 EACVI/ASE Recommendations for the Evaluation of Left Ventricular Diastolic Function (LVDF) provides flow-diagrams to categorize patients. Parameters used include left atrial volume, Doppler-derived transmitral and mitral annular velocities, and systolic PA pressure (sPAP). There are no dedicated criteria to assess the diastolic function in pulmonary arterial hypertension (PAH). Additionally, diseases such as scleroderma can result in both PAH and PVH, thus including sPAP may alter LVDF diagnostic reliability in this population. Purpose Because elevated PAP is fundamental to PAH, we hypothesized that the EACVI/ASE diastolic function algorithm has a lower predictive value in correctly classifying diastolic function in scleroderma. Methodology We performed a single-center retrospective analysis of scleroderma patients who underwent complete echocardiography and comprehensive right and left heart catheterization for PH evaluation. PH categorization was defined using the 6th World Symposium hemodynamic definitions (PAH as mPAP ≥20 mmHg, PCWP ≤15 mmHg, PVR ≥ 3 WU). Diastolic function categorization used 2016 EACVI/ASE recommendations. Index catheterization and echocardiogram closest to cardiac catheterization were analyzed. Results 260 patients underwent evaluation and 63 were diagnosed with PH. PAH was diagnosed in 35 (age 64 ±10, mPAP 55± 18 mmHg, LVEF 60 ± 6%) and PVH in 28 (age 65 ± 10, mPAP 34 ± 14 mmHg, LVEF 63 ± 6%). Of the PAH patients, 20 had normal LVEDP (≤ 12 mmHg) and 15 increased LVEDP. In the PAH normal LVEDP patients, the EACVI algorithm classified diastolic function as normal in 25%, grade 2 in 5%, Grade 3 in 5%, and "indeterminate" in 65%. In the PAH group with increased LVEDP (> 12 mmHg), 27% were incorrectly identified as normal, 7% as grade 2 dysfunction, and 66% as indeterminate. The diastolic function algorithm has a sensitivity of 27% and specificity of 75% to diagnose a LVEDP ≤ 12 mmHg, with an AUC of 0.508 (p = 0.91). With exclusion of sPAP from the algorithm, indeterminate cases in both PAH groups were reclassified as normal, resulting in improved sensitivity (93%) but poorer specificity (10%), and a similar AUC (0.517, p = 0.72). In PVH patients, the algorithm performed better with a sensitivity of 63% and specificity of 83% to predict LVEDP > 12 mmHg with AUC 0.773, p = 0.017. Conclusion In scleroderma patients with PAH, the EACVI diastolic algorithm performs poorly and is confounded by including PAP as a parameter. The sensitivity of the algorithm is improved by the exclusion of sPAP although with reduced specificity. It remains inadequate to reliably diagnose normal LVEDP. While useful in other populations, algorithm modifications including exclusion of PAP, must be employed in suspected scleroderma PAH.

Assessment of the REPLACE study composite endpoint in the PATENT

A proportion of patients with PAH have an insufficient response to phosphodiesterase-5 inhibitors (PDE5i) and do not reach treatment goals. Efficacy of PAH therapies has been assessed by functional measures such as 6MWD and WHO FC. However, mortality in PAH is usually related to RV failure. In the open-label RESPITE study, patients who switched from PDE5i to the soluble guanylate cyclase stimulator riociguat experienced improvements in 6MWD, WHO FC and NT-proBNP, and also hemodynamic parameters such as PVR and cardiac index. We performed a post hoc analysis of hemodynamic parameters to determine if switch to riociguat improved parameters of right ventricular function in patients with an insufficient response to PDE5i.

Intravenous (IV) epoprostenol (epo) is an approved PAH therapy. In contrast to epo-GM (Flolan®), which contains glycine and mannitol, epo-AS (Veletri®) contains arginine and sucrose, resulting in greater stability at room temperature and improved convenience of use. The EPITOME-2 program investigated the long-term safety and tolerability of epo-AS in PAH patients (pts) previously treated with epo-GM. EPITOME-2 extension (NCT01105117) is an extension of the prospective, single-arm, open-label Phase IIIb core study EPITOME-2 (NCT01431716). EPITOME-2 extension evaluated long-term safety of epo-AS, based on adverse events (AE), serious AEs (SAE) and reasons for premature discontinuation. PAH pts were transitioned from epo-GM to epo-AS and treated with epo-AS for 3 months in the core study and until access to commercially available epo-AS or discontinuation in the extension. Final data from the core and extension study are presented on the 41 pts who were transitioned to epo-AS. The majority of pts had IPAH (76%) and were in functional class II (73%) with a median (range) duration of PAH of 5.4 (1.6-37.1) yrs and epo-GM exposure of 3.5 (1.0-14.5) yrs. The median (range) dose of epo-GM prior to transition was 25.0 (7-76) ng/kg/min and epo-AS exposure during the entire treatment period was 2.7 (0.8-4.2) yrs. All pts had ≥1 AE; headache, nasopharyngitis, dyspnea, PAH worsening, diarrhea, extremity pain, cough, fatigue and jaw pain were the most frequent. The majority (85%) of AEs were of mild/moderate intensity. 88% of pts reported ≥1 SAE, the most frequent being catheter site infection, PAH worsening, lung transplant and right ventricular failure (RVF). AEs associated with the delivery system were reported in 73% of pts and included functional complications related to the device (54%), cutaneous complications at catheter site (15%) and local and systemic infections (each 22%). 10 pts prematurely discontinued: lung-transplant (6), sudden death (1), RVF requiring venous-arterial extracorporeal support (1), thrombocytopenia (1) and pt/investigator decision (1). The safety profile of long-term epo-AS in PAH pts appeared consistent with the known safety profile of IV epo and symptoms associated with the underlying disease and its progression. No new safety concerns were identified.

Die aktuellen Behandlungsleitlinien für PAH empfehlen, die betroffenen Patienten unter hämodynamischen, klinischen und funktionellen Aspekten zu untersuchen. Die Studie PATENT-1 diente der Beurteilung von Riociguat, eines neuartigen sGC-Stimulators, im Hinblick auf die Behandlung der PAH.

In der Studie PATENT-1 führte Riociguat bei Patienten mit PAH zu einer signifikanten Verbesserung der Sechs-Minuten-Gehstrecke (6MWD) und einer Reihe sekundärer Endpunkte, wie z.B. Hämodynamik, NT-proBNP und Funktionsklasse gemäß WHO. Für einige dieser Parameter wurden Schwellenwertkriterien definiert, die mit einem positiven klinischen Ergebnis korrelieren.