Comparison of different treatment strategies in patients with chronic thromboembolic pulmonary hypertension: a single centre real-world experience.

BACKGROUND: Pulmonary endarterectomy (PEA) has been the most effective therapy for chronic thromboembolic pulmonary hypertension (CTEPH). However, there is a substantial proportion of patients deemed not operable in whom other treatment strategies are available: medical therapy and balloon pulmonary angioplasty (BPA). We aimed to compare different CTEPH treatment strategies effect in a real-world setting. METHODS: All patients with CTEPH referred to our centre were included. We compare the short-term clinical, functional, exercise and haemodynamic effect of medical therapy (irrespective of subsequent treatment strategies), PEA and BPA (irrespective of previous/subsequent treatment strategies); we also describe the long-term outcome of the different patient groups. RESULTS: We included 467 patients (39% were treated only with medical therapy, 43% underwent PEA, 13% underwent BPA and 5% were not treated with any therapy). Patients treated only with medical therapy were the oldest; compared to patients undergoing PEA, they had a lower exercise capacity, a higher risk profile and gained a lower haemodynamic, functional and survival benefit from the treatment. Patients undergoing BPA had a lower haemodynamic improvement but a comparable functional, exercise and risk improvement and a similar survival compared to patients undergoing PEA; their survival is anyway better than patients undergoing only medical treatment. Untreated historical control patients had the worst survival. CONCLUSIONS: We confirm the superiority of PEA compared to any alternative treatment in CTEPH patients and we observe that BPA, in patients deemed not operable or with persistent/recurrent PH after PEA, leads to a better outcome than medical therapy alone.

Pulmonary Arterial Hypertension Associated with Portal Hypertension and HIV Infection: Comparative Characteristics and Prognostic Predictors.

BACKGROUND: Pulmonary arterial hypertension (PAH) may complicate both portal hypertension (Po-PAH) and HIV infection (HIV-PAH). These two conditions, however, frequently coexist in the same patient (HIV/Po-PAH). We evaluated clinical, functional, hemodynamic characteristics and prognostic parameters of these three groups of patients. METHODS: We included patients with Po-PAH, HIV-PAH and HIV/Po-PAH referred to a single center. We compared clinical, functional and hemodynamic parameters, severity of liver disease [Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease-Na (MELD-Na) scores], CD4 count and highly active antiretroviral therapy (HAART) administration. Prognostic variables were identified through Cox-regression analysis. RESULTS: Patients with Po-PAH (n = 128) were the oldest, patients with HIV-PAH (n = 41) had the worst hemodynamic profile and patients with HIV/Po-PAH (n = 35) had the best exercise capacity. Independent predictors of mortality were age and CTP score for Po-PAH, HAART administration for HIV-PAH, MELD-Na score and hepatic venous-portal gradient for HIV/Po-PAH. CONCLUSIONS: Patients with HIV/Po-PAH are younger and have a better exercise capacity than patients with Po-PAH, have a better exercise capacity and hemodynamic profile compared to patients with HIV-PAH, and their prognosis seems to be related to the hepatic disease rather than to HIV infection. The prognosis of patients with Po-PAH and HIV-PAH seems to be related to the underlying disease.

Progress in the treatment of acute pulmonary embolism and chronic thrombo-embolic pulmonary hypertension/disease.

The combination of an initial clinical approach aimed at evaluating the early risk of mortality with subsequent diagnostic and therapeutic approaches articulated on the overall patient's profile is recommended in acute pulmonary embolism (PE). The presence of pulmonary hypertension associated with the persistence of chronic vascular obstructions in the pulmonary arteries after one or more acute thrombo-embolic events identifies a condition defined as chronic thrombo-embolic pulmonary hypertension (CTEPH). The evolution of technology and knowledge in the field of imaging has allowed us to qualify the computed tomography angiography of the pulmonary arteries as the gold standard for the diagnostic confirmation of both acute PE and CTEPH. In both these conditions, the first therapeutic step is the immediate initiation of anticoagulant therapy. In acute high-risk PE, in addition to anticoagulant therapy, thrombolytic therapy is recommended; in the event of contraindications to thrombolysis, surgical embolectomy or percutaneous catheter-directed treatment represents viable treatment options. In CTEPH, the combination of data collected from cardiac catheterization, computed tomography angiography, and conventional angiography of pulmonary arteries allows a team of experts to identify candidates for pulmonary endarterectomy surgery. Inoperable patients should be considered for percutaneous balloon angioplasty of the pulmonary arteries which can improve patients' symptoms, quality of life, and prognosis.

Is Pulmonary Artery Pulsatility Index (PAPi) a Predictor of Outcome after Pulmonary Endarterectomy?

Background: Pulmonary endarterectomy (PEA) is the gold standard therapy for chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally, pulmonary vascular resistance (PVR) represents the main prognostic factor after surgery. The pulmonary artery pulsatility index (PAPi) has been proposed for the assessment of RV in advanced heart failure, but it has never been applied in CTEPH patients. The aim of the present study is to describe PAPi in patients who underwent PEA, before and after surgery, and to define its predictive impact on postoperative outcomes. Methods: We retrospectively reviewed 188 consecutive adult patients who underwent PEA, between December 2003 and December 2021. PAPi was calculated for 186 patients and reported. Patients were partitioned in two groups using median preoperative PAPi as cutoff value: Group 1 with PAPi ≤ 8.6 (n = 94) and Group 2 with PAPi > 8.6 (n = 92). The propensity-score-matched analysis identified 67 pairs: Early outcomes were compared between two groups. Results: Mean preoperative PAPi was 10.3 ± 7.2. Considering matched populations, no differences emerged in terms of postoperative hemodynamics; Group 1 demonstrated higher 90-day mortality significance (10.4% vs. 3.0%, p = 0.082); the need for mechanical circulatory support (MCS) was similar, but successful weaning was unlikely (25% vs. 85.7%, p = 0.032). Conclusions: Mean PAPi in the CTEPH population is higher than in other diseases. Low PAPi (≤8.6) seems to be associated with lower postoperative survival and successful weaning from MCS.

Therapeutic alternatives in chronic thromboembolic pulmonary hypertension: from pulmonary endarterectomy to balloon pulmonary angioplasty to medical therapy. State of the art from a multidisciplinary team.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with a very complex pathophysiology differing from other causes of pulmonary hypertension (PH). It is an infrequent consequence of acute pulmonary embolism that is frequently misdiagnosed. Pathogenesis has been related to coagulation abnormalities, infection or inflammation, although these disturbances can be absent in many cases. The hallmarks of CTEPH are thrombotic occlusion of pulmonary vessels, variable degree of ventricular dysfunction and secondary microvascular arteriopathy. The definition of CTEPH also includes an increase in mean pulmonary arterial pressure of more than 25 mmHg with a normal pulmonary capillary wedge of less than 15 mmHg. It is classified as World Health Organization group 4 PH, and is the only type that can be surgically cured by pulmonary endarterectomy (PEA). This operation needs to be carried out by a team with strong expertise, from the diagnostic and decisional pathway to the operation itself. However, because the disease has a very heterogeneous phenotype in terms of anatomy, degree of PH and the lack of a standard patient profile, not all cases of CTEPH can be treated by PEA. As a result, PH-directed medical therapy traditionally used for the other types of PH has been proposed and is utilized in CTEPH patients. Since 2015, we have been witnessing the rebirth of balloon pulmonary angioplasty, a technique first performed in 2001 but has since fallen out fashion due to major complications. The refinement of such techniques has allowed its safe utilization as a salvage therapy in inoperable patients. In the present keynote lecture, we will describe these therapeutic approaches and results.

A pragmatic approach to risk assessment in pulmonary arterial hypertension using the 2015 European Society of Cardiology/European Respiratory Society guidelines.

OBJECTIVE: To optimise treatment of patients with pulmonary arterial hypertension (PAH), the 2015 European Society of Cardiology/European Respiratory Society guidelines recommend using risk stratification, with the aim of patients achieving low-risk status. Previous analyses of registries made progress in using risk stratification approaches, however, the focus is often on patients with a low-risk prognosis, whereas most PAH patients are in intermediate-risk or high-risk categories. Using only six parameters with high prognostic relevance, we aimed to demonstrate a pragmatic approach to individual patient risk assessment to discriminate between patients at low risk, intermediate risk and high risk of death. METHODS: Risk assessment was performed combining six parameters in four criteria: (1) WHO functional class, (2) 6 min walk distance, (3) N-terminal pro-brain natriuretic peptide (BNP)/BNP plasma levels or right atrial pressure and (4) cardiac index or mixed venous oxygen saturation. Assessments were made at baseline and at first follow-up after 3-4 months. RESULTS: 725 PAH treatment-naive patients were analysed. Survival estimates between risk groups were statistically significant at baseline and first follow-up (p<0.001), even when the analysis was performed within PAH etiological subgroups. Similar results were observed in 208 previously treated PAH patients. Furthermore, patients who remained at or improved to low risk had a significantly better estimated survival compared with patients who remained at or worsened to intermediate risk or high risk (p≤0.005). CONCLUSION: The simplified risk-assessment method can discriminate idiopathic, connective-tissue-disease-associated and congenital-heart-disease-associated PAH patients into meaningful high-risk, intermediate-risk and low-risk groups at baseline and first follow-up. This pragmatic approach reinforces targeting a low-risk profile for PAH patients.

[Progress in the treatment of pulmonary vascular diseases]. / Progressi nel trattamento delle malattie della circolazione polmonare.

Multiple progresses have been achieved in pulmonary vascular diseases in the last decades, including the areas of pulmonary hypertension and pulmonary thromboembolic disease. The increase in knowledge has been accomplished in pathophysiological, clinical and treatment domains and has included as examples the discovery of gene mutations related to the hereditary forms of pulmonary arterial hypertension and the proposals of personalized treatment algorithms in patients with acute pulmonary embolism, chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension, validated in this specific area by more than 45 randomized controlled trials. The diagnostic processes have been refined, increasing the awareness that appropriate and precise diagnosis is essential for the optimal treatment strategy. The drugs approved for pulmonary arterial hypertension are recommended in this group and in specific patients with chronic thromboembolic pulmonary hypertension but are contraindicated in patients with pulmonary hypertension due to left heart and lung diseases. In pulmonary vascular diseases, the therapy cannot be considered as a simple prescription of medications and interventions but is a complex strategy which includes baseline patients' risk stratification, initial therapy, long-term follow-up and treatment adjustments when required. Today, computed tomography pulmonary artery angiography is the gold standard for diagnosis in both acute pulmonary embolism and chronic thromboembolic pulmonary hypertension. In this last condition, the combination with data derived from the right heart catheterization and the traditional pulmonary artery angiography, allows to a team of experts to decide if the patient is a candidate to surgical pulmonary endarterectomy or to percutaneous pulmonary artery balloon angioplasty which may improve symptoms, quality of life and prognosis.

[Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: 5 years of experience in Italy]. / L'angioplastica delle arterie polmonari nel cuore polmonare cronico tromboembolico: 5 anni di esperienza in Italia.

BACKGROUND: Balloon pulmonary angioplasty (BPA) represents a therapeutic option for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) in patients who are not eligible for surgical pulmonary endarterectomy (PEA) or with persistent/recurrent symptomatic pulmonary arterial hypertension after PEA. This study evaluated the safety of BPA during 5 years of experience of the only Italian center systematically performing this procedure. METHODS: The BPA program was activated at the S. Orsola Polyclinic in Bologna in June 2015. Life-threatening periprocedural complications were defined as: death <30 days, need for cardiopulmonary support, hemoptysis with the need for endotracheal intubation. Serious complications were vascular complications requiring surgical or percutaneous intervention. Other endpoints of interest were: hemoptysis, pulmonary vascular damage with or without hemoptysis, and pulmonary reperfusion injury with high-resolution computed tomography lung scan at 24 h. RESULTS: From June 2015 to September 2020, 50 patients (45% male, median age 68 years), 42 inoperable and 8 with persistent/recurrent pulmonary hypertension after PEA, underwent 156 BPA procedures at our institution. There was one life-threatening complication (2% of patients, 0.06% of the procedures), i.e. severe hemoptysis requiring endotracheal intubation, and four serious complications (8% of the patients, 2.6% of the procedures), i.e. one pulmonary artery perforation requiring percutaneous treatment and three access-site vascular complications requiring surgery. There were no deaths <30 days. Pulmonary reperfusion injury occurred in 37 patients (74%) for a total of 96 sessions (62%). However, reperfusion injury was limited and with subclinical course in most cases. CONCLUSIONS: This study confirmed the relative safety of BPA in patients with CTEPH who are not candidates for heart surgery or with persistent pulmonary hypertension after PEA in the first large Italian experience.

[Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension:a paradigmatic case report]. / Angioplastica delle arterie polmonari nel cuore polmonare cronico tromboembolico: un caso clinico paradigmatico.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complex disease where organized pulmonary thrombi and progressive vascular remodeling of the pulmonary arterial tree act synergistically to increase pulmonary vascular resistance and cause pulmonary hypertension. Balloon pulmonary angioplasty (BPA) has gained a renewed interest for the treatment of patients with CTEPH who are not undergoing surgery with pulmonary endarterectomy (PEA) or with persistent/recurrent pulmonary hypertension after PEA and has shown promising results in several observational studies conducted to date. We describe the case of a 42-year-old man with inoperable CTEPH in NYHA functional class III who normalized functional capacity, hemodynamic profile and main hemodynamic parameters after three BPA sessions.

Pulmonary hypertension due to left heart disease: analysis of survival according to the haemodynamic classification of the 2015 ESC/ERS guidelines and insights for future changes.

AIMS: Pulmonary hypertension (PH) is a relevant complication of left heart disease (LHD). The 2015 ESC/ERS PH guidelines report two different haemodynamic subsets of PH due to LHD (PH-LHD) based on levels of pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG): isolated post-capillary PH (Ipc-PH) and combined post- and pre-capillary PH (Cpc-PH). The objective of this study is to evaluate the prognostic value of Ipc-PH and Cpc-PH. METHODS AND RESULTS: Data from 276 consecutive incident patients with PH-LHD were included. According to the guidelines, Ipc-PH is defined by DPG <7 mmHg and/or PVR ≤3 Wood units (WU) and Cpc-PH by DPG ≥7 mmHg and/or PVR >3 WU. Using this definition, we identified three patient groups: Ipc-PH with both normal PVR and DPG (108 patients); Cpc-PH with both increased PVR and DPG (66 patients); and an intermediate group with either increased PVR or DPG (102 patients). Survival was estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Patients with Ipc-PH had better survival compared with the group of patients with Cpc-PH (P = 0.026) and the intermediate group (P = 0.025). No survival difference was detected between patients with Cpc-PH and the intermediate group (P = 0.891). Patients with normal PVR had a better survival compared with those with elevated PVR (P = 0.012); while no difference was observed according to the level of DPG (P = 0.253). CONCLUSION: Patients with Ipc-PH have a better prognosis compared with patients with Cpc-PH and with patients with isolated increase of PVR or DPG. Pulmonary vascular resistance has a better predictive value than DPG in patients with PH-LHD.

Anticoagulant treatment in patients with pulmonary arterial hypertension associated with systemic sclerosis: More shadows than lights.

Pulmonary arterial hypertension is a chronic and progressive disease characterized by elevated pulmonary artery pressure and pulmonary vascular resistance leading to heart failure and premature death. Pulmonary arterial hypertension is characterized by proliferative and obstructive lesions in the distal pulmonary arteries and some descriptions include also thrombotic lesions. Despite this, in an era when multiple effective pulmonary arterial hypertension therapies are available, the role of anticoagulation in the treatment of pulmonary arterial hypertension remains uncertain. In particular, anticoagulant treatment in pulmonary arterial hypertension associated with connective tissue disease seems to be associated with unfavorable risk to benefit ratio due to an increased rate of bleeding from the gastrointestinal tract. However, anticoagulation may be required in conditions with increased thrombophilia like in the presence of lupus anticoagulant phenomenon or in the presence of anticardiolipin antibodies.

Left Main Coronary Artery Compression in Patients With Pulmonary Arterial Hypertension and Angina.

BACKGROUND: Left main coronary artery (LMCA) compression is increasingly recognized as a cause of angina in pulmonary arterial hypertension (PAH). OBJECTIVES: This study aimed to evaluate the prevalence of LMCA extrinsic compression from a dilated pulmonary artery (PA) in patients with PAH and angina or angina-like symptoms, determine the usefulness of screening with computed tomography coronary angiography (CTCA), and assess the safety and efficacy of percutaneous coronary interventions (PCIs). METHODS: All patients with PAH and angina or angina-like symptoms attending the center between May 1, 2008, and December 31, 2013, underwent CTCA. Patients with confirmed LMCA stenosis on selective coronary angiography had PCI. RESULTS: Of 765 patients with PAH, 121 had angina or angina-like symptoms. Ninety-four patients had abnormal CTCA based on the relationship between the PA and the LMCA and underwent selective coronary angiography. LMCA stenosis ≥50% was detected in 48 of the 94 patients. Forty-five patients underwent PCI with stenting, of whom 41 had sustained angina symptom relief. The 3 other patients had surgical PA reduction plasty. Nine months after PCI, 5 patients had LMCA restenosis and PCI was successfully repeated. The best predictor of LMCA stenosis ≥50% was a PA diameter ≥40 mm. Rates for death or double-lung transplant and the composite rates for death, double-lung transplant, or restenosis at 36 months were 5% and 30%, respectively. CONCLUSIONS: The prevalence of LMCA compression in patients with PAH and angina is high. These results suggest that CTCA is indicated in patients with PAH and angina or angina-like symptoms. PCI was well tolerated, improved symptoms, and resulted in favorable long-term outcomes.