Pulmonary hypertension (PH) and its associated diseases are still associated with a poor prognosis and reduced life expectancy.
The Department of Pulmonology at the University Hospital Zurich (USZ) conducts research into various forms and aspects of PH. The results of these investigations were presented at the ERS Congress 2023.
Pulmonary hypertension is a complex clinical condition. The most common cause of this is left heart disease. However, little is known about the epidemiology and prognosis of combined post- and precapillary PH (CpcPH). Dr. Anna Titz and her colleagues got to the bottom of this [1].
The Swiss PH Registry is a collaboration of 13 Swiss hospitals that was established in 1998 and has been recording patients with newly diagnosed pulmonary hypertension since 2000. The researchers focused their analysis on patients with combined post- and precapillary hypertension, a subgroup of group 2 PH defined by an occlusion pressure of >15 Wood units and a resistance pressure of >2 Wood units. The aim of their study was to evaluate the baseline characteristics of the cohort and the long-term outcome, to determine a possible association between baseline variables and all-cause mortality, and to analyze whether the risk assessment stratification defined and validated for PAH could be applicable.
They conducted a retrospective survival analysis of the Swiss PH registry, which included CpcPH patients registered between 01/2001 and 06/2019. Baseline patient characteristics (age, sex, mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), and risk factors including WHO-FC, 6-minute walk distance (6MWD) and NT-proBNP, treatment, days of follow-up, and events (death or loss to follow-up) at the last visit were analyzed using Kaplan Meier and Cox regression.
mPAP >46 mmHg was associated with higher mortality
231 patients (59.3% women, age 65±12 years, mPAP 48±11 mmHg, PAWP 21±5 mmHg, PVR 7.2±4.8 WU) were included. “Surprisingly, our data show that 47% of our cohort received PH-targeted medication. It is well known that there is little and conflicting evidence for targeted medication in group 2 PH patients,” recalled Dr. Titz. “Our data show that there is no significant correlation between targeted PH medication and survival.”
In addition, Kaplan-Meier analysis showed that women had a significantly longer survival than the average. An mPAP value of more than 46 mmHg was associated with a higher mortality rate. The four-level risk assessment tool was able to stratify survival by showing that high-risk patients had higher mortality than low- and intermediate-risk patients. On the other hand, a significant influence of age or PVR on survival could not be determined.
Risk stratification based on non-invasively determined risk factors such as WHO-FC, 6MWD and NTproBNP, as proposed for pulmonary arterial hypertension, could be helpful in the treatment of these patients in the future, Dr. Titz concluded.
Good long-term survival in CTEPH with PEA and BPA
For patients with chronic thromboembolic pulmonary hypertension (CTEPH), several treatment approaches can be considered, consisting of pulmonary endarterectomy (PEA), pulmonary balloon angioplasty (BPA) and drug therapy. Paula Appenzeller, USZ and Royal Papworth Hospital, Cambridge, and colleagues evaluated the long-term outcomes of a national cohort from the UK between 2015 and 2022, when all three treatment options were available [2].
“CTEPH is a form of precapillary pulmonary hypertension that occurs as an acute complication of acute pulmonary embolism. In the past, the only treatment available was surgical pulmonary endarterectomy (PEA), which only targets proximal foci of disease. However, there are more and more patients with distal disease, so balloon pulmonary angioplasty (BPA) and drug therapy have been introduced more recently,” explained the pulmonologist. Many patients therefore have overlapping proximal and distal disease, which makes a multimodal treatment approach necessary. The researchers’ analysis was carried out at the Royal Papworth Hospital NHS Foundation Trust in Cambridge, UK. More than 1350 patients were included, with the PEA group representing the largest group (n=1102). The PEA and BPA group (n=121) were national cohorts, as surgery and interventions in the UK are only performed in Cambridge, while the non-interventional group (n=143) consisted of only one center and was highly heterogeneous. It included both surgically inoperable conditions and patients who are technically operable but have other barriers to surgery such as co-morbidities. Once patients in the UK were diagnosed with CTEPH, their cases were discussed at a national CTEPH multidisciplinary team (MDT) meeting according to the anatomical distribution of chronic clots and individual risks and benefits.
The age at the start of treatment was very different in the three groups: the participants in the PEA group were 60 years old on average, 67 years old in the BPA cohort and 74 years old in the non-interventional group. In addition, the scientists found that both PEA and BPA showed a reduction in mean pulmonary arterial pressure and pulmonary vascular resistance at follow-up. However, although PEA appears to cause a greater reduction in hemodynamics, the functional results in terms of symptoms and the 6-minute walk test were identical to those of the BPA group.
The 3-year survival rate was 91% for the PEA cohort, 96% for the BPA group and 64% for the non-interventional group. BPA and PEA thus show no significant difference in the survival rate after three years (Fig. 1). “If we look at the curve, we can see an initial drop immediately after the start of the intervention in the PEA group, which is mainly due to early deaths after the operation,” explained Appenzeller. There was no difference in the survival rate of patients who died before the first follow-up examination (95% vs. 96%).
Appenzeller concludes that excellent long-term survival rates can be observed in CTEPH patients who have been treated with an intervention. Of the patients referred to the national CTEPH MTD, most had proximal disease, so 82% received PEA as treatment. In order to offer multimodal treatment and optimize the outcome for the individual patient, an experienced MDT is required for therapy selection, as the treatments can be used alongside each other but are not interchangeable as they target different disease distributions.
Stable PVD patients tolerate high altitude air
Travel to high-altitude tourist areas is becoming increasingly popular, including among potentially vulnerable groups such as people with precapillary pulmonary hypertension due to pulmonary vascular disease (PVD). There is little evidence to advise PVD patients for their upcoming high altitude trips.
Simon Raphael Schneider and colleagues investigated altitude-related adverse health effects (ARAHE) during an overnight stay at 2500 m altitude and whether additional oxygen reverses the effects of altitude. The participants were first examined at a low altitude in Zurich (470 m) and then at an altitude of 2500 m on the Säntis or vice versa.
In their randomized cross-over study, the researchers finally included 27 (44% female) stable patients with PVD (including pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension) and exposed them to an altitude of 2500 m for about 30 hours. ARAHE requiring O2 therapy was defined as severe hypoxemia (SpO2 <80% for >30 min). On the second day at altitude, right heart function was examined using echocardiography, acute mountain sickness (AMS) and arterial blood gases, among other things.
Those patients who experienced severe hypoxemia were treated with supplemental oxygen, and the secondary endpoint was whether the supplemental oxygen improved oxygenation, as well as right heart hemodynamic values at rest and 6-minute walk distance. In total, the researchers studied 65 patients, including 27 stable patients with PVD, 12 of whom were female and most of whom were NYHA (New York Heart Association) class II. A total of ten patients suffered severe hypoxemia (SPO2 <80% >30 min): one after several hours at altitude and most at the beginning of the first night at 2500 m. Seven patients suffered from acute mountain sickness (AMS). Fortunately, none of them had to be evacuated or wanted to descend earlier than planned. This allowed them to continue with the additional oxygen and carry out all the tests with oxygen.
The arterial blood gas analysis revealed that those patients who received additional oxygen at altitude had a significantly lower oxygen content, but also a lower PaO2 and a significantly higher carbon dioxide (CO2) content at low altitude in Zurich. On the other hand, the patients who did not receive oxygen at altitude had a strong tendency towards respiratory alkalosis at 2500 m. “We can therefore conclude that the patients who received oxygen also benefited from it.”
Looking at the hemodynamic values, which were also measured on the second day during the resting phase at altitude, there was no significant change in heart rate and tricuspid pressure gradient in the patients who received supplemental oxygen. In the patients who did not receive supplemental oxygen, the heart rate changed, but the tricuspid pressure gradient also increased.
“In summary, we can say that stable patients with PVD who have been exposed for up to two days at 2500 m for up to 30 hours tolerate this altitude subjectively quite well,” says the pulmonologist. However, more than a third (37%) of patients experienced severe hypoxemia, which could be corrected with supplemental oxygen. Significant physiological differences between 470 m and 2500 m were observed in the non-hypoxemic patients, but no longer in the patients receiving O2.
Congress: ERS 2023
Source: European Respiratory Society (ERS) International Congress 2023, Milan; Session “Novelties in pulmonary hypertension management”; 10.09.2023.
- Titz A: Long-term outcome of patients with combined post- and precapillary pulmonary hypertension (Presentation ID 747).
- Appenzeller P: Long term outcome in chronic thromboembolic pulmonary hypertension in the multimodality treatment era: a UK national cohort analysis (Presentation ID 741).
- Schneider SR: Altitude related adverse effect and therapeutic benefit of supplemental oxygen in patients with pulmonary vascular disease during an overnight stay at 2500 m (Presentation ID 748).
InFo PNEUMOLOGIE & ALLERGOLOGIE 2023; 5(4): 22–24
