The Opening Plenary session started off the meeting, and pulmonary vascular disease was the first abstract reported at ISHLT 2022! In this presentation Justin Chan, MD, (University Health Network, Toronto, ON Canada), reported on sex differences in outcomes of patients undergoing pulmonary endarterectomy (PEA) for a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH).

Dr. Chan’s report consisted of a retrospective study of 401 patients who underwent PEA at the University Health Network in Toronto, Canada. They compared the 203 female patients to the 198 male patients and assessed the outcomes of survival, functional class, and need for post-operative vasodilator therapy. Interestingly, there were sex differences in clinical outcomes, with female patients having less improvement in the pulmonary vascular resistance (final pulmonary vascular resistance after PEA, 437 Dynes∙s∙cm^-5 vs 324 Dynes∙s∙cm^-5 in males, p<0.01). Survival was similar at 10 years, but female patients had a worse functional class, increased symptom burden, and increased need for vasodilator therapy. In addition to their clinical outcomes assessment, there were five patients who underwent single cell RNA sequencing (3 males and 2 females), with an overexpression of TGF- β1 in endothelial cells in females.

In a robust discussion following the abstract presentation, David Jenkins, FRCS,(Papworth Hospital, Cambridge UK) asked Dr. Chan to postulate on why female patients fared poorly as compared to their male counterparts. Ultimately, it was felt that female patients were more susceptible to having segmental and subsegmental disease, and less central disease, potentially explaining the decreased response to PEA surgery.
   

The first symposium in the pulmonary vascular disease interdisciplinary network was a series of three controversial debates related to pulmonary hypertension.

The first debate was whether invasive hemodynamics were essential for the risk stratification of patients with pulmonary arterial hypertension (PAH). In this debate, Sophia Airhart, MD, (Providence Heart and Vascular Institute, Portland, OR USA), made the argument that patients with pulmonary hypertension need the gold standard measurement of pulmonary pressures, an invasive right heart catheterization when doing risk assessments. Her argument focused on how clinician gestalt does not adequately discriminate risk in patients with pulmonary arterial hypertension (PAH). Further, she argued that the various risk prediction algorithms in PAH utilize invasive hemodynamics in their assessment.

In rebuttal, Marc A. Simon, MD, (UCSF Medical Center, San Francisco, CA USA) argued that the use of various imaging modalities, including echocardiogram and cardiac magnetic resonance imaging, provide sufficient evidence to discriminate risk, and that we should be more judicious in whom we put through a right heart catheterization. At the end of the debate the audience in the room sided with the need for invasive hemodynamics in risk assessment.

The second debate was focused on whether patients with interstitial lung disease associated pulmonary arterial hypertension (ILD-PH) should be treated with approved PAH therapies. This classic debate in pulmonary hypertension was given renewed vigor this year given the results of a clinical trial (INCREASE trial) assessing the use of inhaled treprostinil in patients with ILD-PH (Waxman et al. NEJM 2021).

The debate started off with a vigorous defense of the use of vasodilators in PH-ILD by Colin Church, MD, PhD, (Golden Jubilee Hospital, Glasgow, Scotland UK) who argued that the results of the INCREASE trial, which showed improvements in 6MWD, BNP, and time to clinical worsening, justified the use of inhaled treprostinil in select patients with PH-ILD.

On the converse side, Helen Whitford, MBBS, FRACP, (Alfred Hospital, Melbourne, Australia) argued that patients with PH-ILD should not be treated with inhaled treprostinil because there was no long-term outcome data, there is no mortality data, and that the outcome of improvement in 6MWD was modest for a drug with a high burden of use. Further, she cautioned against the use of vasodilators in the population given that it may push back listing for transplantation, and then patients will be sicker at the time of transplantation. At the end of the debate the audience was mostly split, with a slight increase in votes for the use of vasodilators in patients with PH-ILD.

The final debate was on whether patients with symptomatic chronic thromboembolic disease (CTED) should be treated with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty. In the pro-treatment group, David Jenkins, FRCS, (Papworth Hospital, Cambridge, UK) argued in favor of surgery given that CTED can be associated with exercise intolerance, progression to CTEPH, and that patients with CTED can have a significant burden of disease. He displayed the specimens of various CTEPH and CTED patients after PEA and challenged his opponent to pick out those with CTED and not CTEPH.

In opposition was Isabelle Opitz, MD, (University Hospital Zurich, Zurich, Switzerland), who argued that the lack of randomized controlled trial data warranted caution, and that PEA for CTED surgery often results in only mild improvements in 6MWD amongst patients with a fairly low symptom burden. As such, these patients should not undergo major cardiac surgery. At the end of the debate, the audience agreed that CTED should be treated.
   

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DEBATE: Invasive Hemodynamics are Essential for Risk Stratification in PAH (PRO)
Sophia Airhart, MD, Providence Heart and Vascular Institute, Portland, OR USA

DEBATE: Invasive Hemodynamics are Essential for Risk Stratification in PAH (CON)
Marc A. Simon, MD, UCSF Medical Center, San Francisco, CA USA

DEBATE: PH Due to Interstitial Lung Disease (ILD) Should Be Treated with PAH Approved Therapies (PRO)
Colin Church, PhD, Golden Jubilee Hospital, Glasgow UK

DEBATE: PH Due to Interstitial Lung Disease (ILD) Should Be Treated with PAH Approved Therapies (CON)
Helen M. Whitford, MBBS, FRACP, Alfred Hospital, Melbourne, Australia

DEBATE: Symptomatic Chronic Thromboembolic Disease (CTED) Should Be Treated with PEA or BPA (PRO)
David P. Jenkins, FRCS, Papworth Hospital, Cambridge UK

DEBATE: Symptomatic Chronic Thromboembolic Disease (CTED) Should Be Treated with PEA or BPA (CON)
Isabelle Opitz, MD, University Hospital Zurich, Zurich, Switzerland

The first oral session was focused on translating research from the bench to the bedside in the pulmonary vascular disease space.

In a pre-recorded talk entitled “Distinct Endothelial Cell Populations Characterize the Pulmonary Endarterectomy Specimen in Chronic Thromboembolic Pulmonary Hypertension,” H.S. Jeffrey Man, MD, PhD, (University of Toronto, Toronto, ON Canada) reported on the use of human pulmonary endarterectomy (PEA) specimens in five patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this study, the authors performed single-cell RNA sequencing in five CTEPH patients and three controls. They performed a cluster analysis of transcriptional profiles and determined that four of the twenty clusters displayed markers of endothelial cell phenotypes in the organized thrombotic material. The composition of the endothelial cell clusters was different between CTEPH and control, with CTEPH clusters having increased expression of TGFβ1 and P-selectin.

In a live talk entitled “Left Ventricular Diastolic Dysfunction in Chronic Thromboembolic Pulmonary Hypertension,” Dorothée Brunet, MD, MSc, (Marie Lannelongue Hospital, Le Plessis Robinson, France) reported on a pig model of CTEPH. In this study, six piglets underwent weekly embolization of the right lower lobe with a tissue glue, and were compared to six sham-operated animals. The authors assessed left ventricular diastolic function and left ventricular fibrosis at six weeks, showing that there was increased end-diastolic pressure, increased ventricular stiffness, and an increased fibrosis score in the left ventricle of the CTEPH piglets. They also looked at echocardiograms in 102 human patients before and after PEA, finding mild LV diastolic dysfunction in CTEPH patients after PEA.

In a live talk entitled “Balloon Pulmonary Angioplasty Results in Anatomically Operable CTEPH Patients,” Justin Issard, MD, MSc, (Marie Lannelongue Hospital, Le Plessis Robinson, France) reported on a retrospective review of CTEPH patients treated with balloon pulmonary angioplasty (BPA) in patients with CTEPH. Notably, they had 36 patients with proximal disease who could not undergo PEA surgery, either due to comorbidities (27 of 36) or due to patient refusal (9 of 36). Patients that couldn’t undergo PEA due to co-morbidities did improve in functional class and hemodynamics after PEA, however, those who refused surgery did not improve in functional class or in hemodynamics. To the knowledge of the audience, this was the first report on BPA for proximal disease in CTEPH.

In his live talk entitled “Pirfenidon Prevents Experimental Flow-Associated PAH by Suppression of the NLRP3 Inflammasome,” Emmanouil Mavrogiannis, BSc, (University Medical Center Groningen, Groningen, Netherlands) reported on the use of pirfenidone in a rat model for neointimal PAH induced by monocrotaline and aortocaval shunt. The authors noted that high levels of IL-1β and IL-18 are seen in animal models of PAH, and hypothesized that using pirfenidone may suppress inflammasome activation and led to less vascular disease. The rats who were exposed to pirfenidone had decreased inflammasome activation. In addition, rats treated with pirfenidone had reduced mean pulmonary artery pressures.

In a live talk entitled “Impact of Initial Therapeutic Strategy on Long-Term Outcomes in Pulmonary Arterial Hypertension: An Analysis of the PHSANZ Registry,” Katherine Kearney, MBBS, (St Vincents Hospital, Darlinghurst, Australia) reported on the impact of monotherapy and early double combination therapy using the PHSANZ registry. They defined early combination therapy as the use of two or more PAH-specific vasodilators within three months of therapy. There was no difference in transplant-free survival amongst the two groups, however, 6MWD improved greater in the combination therapy group.
   

This oral session was focused on risk stratification in pulmonary arterial hypertension (PAH). Given that many of the presenters were unable to present in person, the moderators Mardi Gomberg-Maitland, MD, MSc, (GW Heart and Vascular Institute, Washington, DC USA) and Marc Simon, MD, (UCSF Medical Center, San Francisco, CA USA) took on a key role, and led a robust discussion on the various abstracts.

In a live talk entitled “Imaging of Improved Right Ventricular Coupling, Risk Status and Survival in Pulmonary Arterial Hypertension,” Roberto Badagliacca, MD, PhD, (Sapienza University of Rome, Rome, Italy) described the benefit of using the ratio of TAPSE/PASP in risk stratification. The authors assessed 677 patients retrospectively and noted an increase in TAPSE/PASP ratio as pulmonary vascular resistance decreased in patients with pulmonary arterial hypertension (PAH). Lower risk patients by REVEAL or ERS/ESC were more likely to have a TAPSE/PASP ≥ 0.35 mm/mmHg than those at intermediate or high risk scores.

In a pre-recorded talk entitled “Risk Assessment in Pulmonary Arterial Hypertension (PAH): Insights from the Inspire Study with LIQ861,” Sandeep Sahay, MD, (Houston Methodist Hospital, Houston, TX USA) reported on the impact of dry powder treprostinil (LIQ861) in risk stratification. In this Phase 3, open-label study, patients who went on LIQ861 were either transitioned from Tyvaso to LIQ861 or were prostacyclin naïve. At baseline, 51% of patients met two or three low risk variables by the French non-invasive criteria. By month eight there were 76% of patients who met two or three low risk criteria. The primary driver of improvement was in the prostacyclin naïve patients.

In a pre-recorded talk entitled “Clinical Variables in Predicting Survival and Hospitalization for Pulmonary Arterial Hypertension Using Harmonized Data,” Zilu Liu, PhD student at The Ohio State University, Columbus, OH USA, harmonized data from seven adult PAH trials: GRIPHON, SERAPHIN, EARLY, COMPASS-2, COMPASS-3, MAESTRO and TRANSIT-1. They then conducted a Cox proportional hazard analysis to study the association between time to death at 30 days and the pulmonary artery pulsatility index (PAPi) and the aortic pulsatility index (API). PAPi was associated with death at 30 days (HR 0.84, 95%CI: 0.73-0.96). In an exciting moment after the presentation, Ray Benza, MD, (The Ohio State University, Columbus, OH USA) told the audience that Zilu Liu had successfully defended her PhD thesis that morning back in Ohio, and was now Dr. Liu. Congratulations, Dr. Liu!

In a pre-recorded talk entitled “Atrial Fibrillation- A Risk Factor for In-Hospital Mortality of Patient with Pulmonary Hypertension,” Sandra Chaparro, MD, (MCVI Baptist Health South, Miami, FL USA) reported on the association between atrial fibrillation and adverse outcomes in PAH using a retrospective analysis of the National Inpatient Sample data. The authors found that patients hospitalized with PAH and atrial fibrillation were at an increased risk of mortality, had longer hospital lengths of stay, and had higher costs per hospitalization than when hospitalized without atrial fibrillation.

In a live talk entitled “Risk Stratification in Patients with Pulmonary Arterial Hypertension and Candidates for Lung or Heart-Lung Transplantation,” Laurent Savale, MD, PhD, (CHU Bicêtre, Le Kremlin Bicetre, France) reported on a retrospective application of the ERS/ESC risk stratification using the invasive French and COMPERA methods, as well as the REVEAL Lite score to patients with PAH who underwent lung transplantation or heart-lung transplantation. They reported 106 patients with PAH who were listed for transplant. Patients who were high risk by the various risk assessment methods suffered from increased mortality after transplant, arguing for earlier listing in these patients.

The final talk of the session was pre-recorded by Georg Hansmann, MD, PhD, (Hannover Medical School, Hannover, Germany). This talk, entitled “Validation of the New Pediatric Pulmonary Hypertension Risk Score by Cardiac Magnetic Resonance Imaging and Speckle Tracking Echocardiography. The European Pediatric Pulmonary Vascular Disease Network (EPPVDN),” explored the validation of a new pulmonary hypertension risk score in pediatric patients using cardiac MRI and speckle tracking echocardiogram, through the European Pediatric Pulmonary Vascular Disease Network (EPPVDN). The authors demonstrated correlations between cardiac MRI and echo parameters with the EPPVDN risk score.