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Article ; Online: How Would I Treat My Own Chronic Thromboembolic Pulmonary Hypertension in the Perioperative Period?

Loosen, Gregor / Taboada, Dolores / Ortmann, Erik / Martinez, Guillermo

Journal of cardiothoracic and vascular anesthesia

2023 Volume 38, Issue 4, Page(s) 884–894

Abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) results from an incomplete resolution of acute pulmonary embolism, leading to occlusive organized thrombi, vascular remodeling, and associated microvasculopathy with pulmonary hypertension (PH). A ... ...

Abstract	Chronic thromboembolic pulmonary hypertension (CTEPH) results from an incomplete resolution of acute pulmonary embolism, leading to occlusive organized thrombi, vascular remodeling, and associated microvasculopathy with pulmonary hypertension (PH). A definitive CTEPH diagnosis requires PH confirmation by right-heart catheterization and evidence of chronic thromboembolic pulmonary disease on imaging studies. Surgical removal of the organized fibrotic material by pulmonary endarterectomy (PEA) under deep hypothermic circulatory arrest represents the treatment of choice. One-third of patients with CTEPH are not deemed suitable for surgical treatment, and medical therapy or interventional balloon pulmonary angioplasty presents alternative treatment options. Pulmonary endarterectomy in patients with technically operable disease significantly improves symptoms, functional capacity, hemodynamics, and quality of life. Perioperative mortality is <2.5% in expert centers where a CTEPH multidisciplinary team optimizes patient selection and ensures the best preoperative optimization according to individualized risk assessment. Despite adequate pulmonary artery clearance, patients might be prone to perioperative complications, such as right ventricular maladaptation, airway bleeding, or pulmonary reperfusion injury. These complications can be treated conventionally, but extracorporeal membrane oxygenation has been included in their management recently. Patients with residual PH post-PEA should be considered for medical or percutaneous interventional therapy.
MeSH term(s)	Humans ; Hypertension, Pulmonary/diagnostic imaging ; Hypertension, Pulmonary/etiology ; Hypertension, Pulmonary/surgery ; Quality of Life ; Chronic Disease ; Pulmonary Embolism/complications ; Pulmonary Embolism/diagnostic imaging ; Pulmonary Embolism/surgery ; Pulmonary Artery/surgery ; Angioplasty, Balloon/methods ; Perioperative Period ; Endarterectomy/methods ; Thromboembolism
Language	English
Publishing date	2023-07-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1067317-9
ISSN	1532-8422 ; 1053-0770
ISSN (online)	1532-8422
ISSN	1053-0770
DOI	10.1053/j.jvca.2023.07.014
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Article ; Online: The Digital 1-Minute Walk Test: A New Patient-centered Cardiorespiratory Endpoint.

Robertson, Lucy / Newman, Joseph / Clayton, Shaun / Ferguson, Mary / Pepke-Zaba, Joanna / Cannon, John / Sheares, Karen / Taboada, Dolores / Bunclark, Katherine / Armstrong, Iain / Ferrer Mallol, Elisa / Davies, Elin Haf / Toshner, Mark

American journal of respiratory and critical care medicine

2024 Volume 209, Issue 6, Page(s) 753–756

MeSH term(s)	Humans ; Walk Test ; Exercise Test ; Walking ; Patient-Centered Care ; Cardiorespiratory Fitness
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Letter
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202310-1855LE
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Article ; Online: The prognostic ability of cardiac output determined by inert gas rebreathing technique in pulmonary hypertension.

Robertson, Lucy / Bunclark, Katherine / Ross, Robert Mackenzie / Cannon, John / Sheares, Karen / Taboada, Dolores / Pepke-Zaba, Joanna / Toshner, Mark

Chronic respiratory disease

2022 Volume 19, Page(s) 14799731221078473

Abstract: This investigation validated the inert gas rebreathing (IGR) technique and determined IGR prognostic ability compared to invasive cardiac output measurements in patients with pulmonary hypertension. IGR compared with thermodilution cardiac output ... ...

Abstract	This investigation validated the inert gas rebreathing (IGR) technique and determined IGR prognostic ability compared to invasive cardiac output measurements in patients with pulmonary hypertension. IGR compared with thermodilution cardiac output demonstrated a moderate bias. IGR technique demonstrated long-term prognostic value comparable to invasive cardiac output in pulmonary hypertension patients.
MeSH term(s)	Cardiac Output ; Humans ; Hypertension, Pulmonary/diagnosis ; Prognosis
Language	English
Publishing date	2022-02-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2211488-9
ISSN	1479-9731 ; 1479-9723
ISSN (online)	1479-9731
ISSN	1479-9723
DOI	10.1177/14799731221078473
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Article ; Online: Natural history of chronic thromboembolic pulmonary disease with no or mild pulmonary hypertension.

Reddy, Sathineni A / Swietlik, Emilia M / Robertson, Lucy / Michael, Alice / Boyle, Sonja / Polwarth, Gary / Screaton, Nick J / Ruggiero, Alessandro / Nethercott, Sarah L / Taboada, Dolores / Sheares, Karen K / Hadinnapola, Charaka / Cannon, John E / Bunclark, Katherine / Jenkins, David / Ng, Choo / Toshner, Mark R / Pepke-Zaba, Joanna

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

2023 Volume 42, Issue 9, Page(s) 1275–1285

Abstract: Background: We describe baseline characteristics, disease progression and mortality in chronic thromboembolic pulmonary disease patients as a function of mean pulmonary artery pressure (mPAP) according to new and previous definitions of pulmonary ... ...

Abstract	Background: We describe baseline characteristics, disease progression and mortality in chronic thromboembolic pulmonary disease patients as a function of mean pulmonary artery pressure (mPAP) according to new and previous definitions of pulmonary hypertension. Methods: All patients diagnosed with chronic thromboembolic pulmonary disease between January, 2015 and December, 2019 were dichotomized according to initial mPAP: ≤ 20 mmHg ('normal') vs 21-24 mmHg ('mildly-elevated'). Baseline features were compared between the groups, and pairwise analysis performed to determine changes in clinical endpoints at 1-year, excluding those who underwent pulmonary endarterectomy or did not attend follow-up. Mortality was assessed for the whole cohort over the entire study period. Results: One hundred thirteen patients were included; 57 had mPAP ≤ 20 mmHg and 56 had mPAP 21-24 mmHg. Normal mPAP patients had lower pulmonary vascular resistance (1.6 vs 2.5WU, p < 0.01) and right ventricular end-diastolic pressure (5.9 vs 7.8 mmHg, p < 0.01) at presentation. At 3 years, no major deterioration was seen in either group. No patients were treated with pulmonary artery vasodilators. Eight had undergone pulmonary endarterectomy. Over 37 months median follow-up, mortality was 7.0% in the normal mPAP group and 8.9% in the mildly-elevated mPAP group. Cause of death was malignancy in 62.5% of cases. Conclusions: Chronic thromboembolic pulmonary disease patients with mild pulmonary hypertension have statistically higher right ventricular end-diastolic pressure and pulmonary vascular resistance than those with mPAP ≤ 20 mmHg. Baseline characteristics were otherwise similar. Neither group displayed disease progression on non-invasive tests up to 3 years. Mortality over 37 months follow-up is 8%, and mainly attributable to malignancy. Further prospective study is required to validate these findings.
MeSH term(s)	Humans ; Hypertension, Pulmonary ; Hemodynamics ; Pulmonary Artery ; Vascular Resistance ; Disease Progression ; Chronic Disease
Language	English
Publishing date	2023-05-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	1062522-7
ISSN	1557-3117 ; 1053-2498
ISSN (online)	1557-3117
ISSN	1053-2498
DOI	10.1016/j.healun.2023.04.016
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Article ; Online: Angiopoietin 2 and hsCRP are associated with pulmonary hemodynamics and long-term mortality respectively in CTEPH-Results from a prospective discovery and validation biomarker study.

Hadinnapola, Charaka M / Southwood, Mark / Hernández-Sánchez, Jules / Bunclark, Katherine / Newnham, Michael / Swietlik, Emilia M / Cannon, John / Preston, Stephen D / Sheares, Karen / Taboada, Dolores / Screaton, Nicholas / Jenkins, David P / Morrell, Nicholas W / Toshner, Mark / Pepke-Zaba, Joanna

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

2022 Volume 42, Issue 3, Page(s) 398–405

Abstract: Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed disease of uncertain etiology. Altered endothelial homeostasis, defective angiogenesis and inflammation are implicated. Angiopoietin 2 (Ang2) impairs acute thrombus ...

Abstract	Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed disease of uncertain etiology. Altered endothelial homeostasis, defective angiogenesis and inflammation are implicated. Angiopoietin 2 (Ang2) impairs acute thrombus resolution and is associated with vasculopathy in idiopathic pulmonary arterial hypertension. Methods: We assessed circulating proteins associated with these processes in serum from patients with CTEPH (n = 71) before and after pulmonary endarterectomy (PEA), chronic thromboembolic pulmonary disease without pulmonary hypertension (CTEPD, n = 9) and healthy controls (n = 20) using Luminex multiplex arrays. Comparisons between groups were made using multivariable rank regression models. Ang2 and high-sensitivity C-reactive protein (hsCRP) were measured in a larger validation dataset (CTEPH = 277, CTEPD = 26). Cox proportional hazards models were used to identify markers predictive of survival. Results: In CTEPH patients, Ang2, interleukin (IL) 8, tumor necrosis factor α, and hsCRP were elevated compared to controls, while vascular endothelial growth factor (VEGF) c was lower (p < 0.05). Ang2 fell post-PEA (p < 0.05) and was associated with both pre- and post-PEA pulmonary hemodynamic variables and functional assessments (p < 0.05). In the validation dataset, Ang2 was significantly higher in CTEPH compared to CTEPD. Pre-operative hsCRP was an independent predictor of mortality. Conclusions: We hypothesize that CTEPH patients have significant distal micro-vasculopathy and consequently high circulating Ang2. Patients with CTEPD without pulmonary hypertension have no discernible distal micro-vasculopathy and therefore have low circulating Ang2. This suggests Ang2 may be critical to CTEPH disease pathogenesis (impaired thrombus organization and disease severity).
MeSH term(s)	Humans ; Angiopoietin-2 ; Biomarkers ; C-Reactive Protein ; Endarterectomy/adverse effects ; Hemodynamics ; Hypertension, Pulmonary/diagnosis ; Hypertension, Pulmonary/etiology ; Hypertension, Pulmonary/metabolism ; Vascular Endothelial Growth Factor A
Chemical Substances	Angiopoietin-2 ; Biomarkers ; C-Reactive Protein (9007-41-4) ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2022-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1062522-7
ISSN	1557-3117 ; 1053-2498
ISSN (online)	1557-3117
ISSN	1053-2498
DOI	10.1016/j.healun.2022.08.021
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Article ; Online: Plasma metabolomics exhibit response to therapy in chronic thromboembolic pulmonary hypertension.

Swietlik, Emilia M / Ghataorhe, Pavandeep / Zalewska, Kasia I / Wharton, John / Howard, Luke S / Taboada, Dolores / Cannon, John E / Morrell, Nicholas W / Wilkins, Martin R / Toshner, Mark / Pepke-Zaba, Joanna / Rhodes, Christopher J

The European respiratory journal

2021 Volume 57, Issue 4

Abstract: Pulmonary hypertension is a condition with limited effective treatment options. Chronic thromboembolic pulmonary hypertension (CTEPH) is a notable exception, with pulmonary endarterectomy (PEA) often proving curative. This study investigated the plasma ... ...

Abstract	Pulmonary hypertension is a condition with limited effective treatment options. Chronic thromboembolic pulmonary hypertension (CTEPH) is a notable exception, with pulmonary endarterectomy (PEA) often proving curative. This study investigated the plasma metabolome of CTEPH patients, estimated reversibility to an effective treatment and explored the source of metabolic perturbations.We performed untargeted analysis of plasma metabolites in CTEPH patients compared to healthy controls and disease comparators. Changes in metabolic profile were evaluated in response to PEA. A subset of patients were sampled at three anatomical locations and plasma metabolite gradients calculated.We defined and validated altered plasma metabolite profiles in patients with CTEPH. 12 metabolites were confirmed by receiver operating characteristic analysis to distinguish CTEPH and both healthy (area under the curve (AUC) 0.64-0.94, all p<2×10
MeSH term(s)	Chronic Disease ; Endarterectomy ; Familial Primary Pulmonary Hypertension ; Humans ; Hypertension, Pulmonary ; Metabolomics ; Pulmonary Embolism/complications
Language	English
Publishing date	2021-04-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.03201-2020
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Zs.A 2322: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 292: Show issues

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Article ; Online: Serial right heart catheter assessment between balloon pulmonary angioplasty sessions identify procedural factors that influence response to treatment.

Hug, Karsten P / Gerry Coghlan, J / Cannon, John / Taboada, Dolores / Toshner, Mark / Sheares, Karen / Ruggiero, Alessandro / Screaton, Nicholas / Jenkins, David / Pepke-Zaba, Joanna / Hoole, Stephen P

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

2021 Volume 40, Issue 10, Page(s) 1223–1234

Abstract: Background: Balloon pulmonary angioplasty (BPA) is delivered as a series of treatments for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) however, there is little published data on the procedural determinants of outcome.!# ...

Abstract	Background: Balloon pulmonary angioplasty (BPA) is delivered as a series of treatments for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) however, there is little published data on the procedural determinants of outcome. Methods: Pre- and post-BPA clinical and hemodynamic data, as well as serial hemodynamic and procedural data at each BPA session were evaluated to determine patient and procedure-related factors that influence hemodynamic response. Results: Per procedure data from 210 procedures in 84 patients and per patient data from 182 procedures in 63 patients with completed treatment and 3-month follow-up were analyzed. A median of 3 (range 1-6) BPA procedures treating a median of 2 segments per procedure (range 1-3) were performed per patient with a median interval between procedures of 42 (range 5-491) days. Clinical outcome correlated with hemodynamic change (pulmonary vascular resistance [ΔPVR] vs Cambridge Pulmonary Hypertension Outcome Review [CAMPHOR] symptom score: p < 0.001, Pearson's r = 0.48, n = 49). Responders to BPA had more severe disease at baseline and 37.5 % of non-responders were post-PEA. There was a dose-response relationship between per procedure and total number of segments treated and hemodynamic improvement (ΔPVR: 1 segment: -0.9%, 2: -14.5%, 3 or more: -16.1%, p < 0.001). Treating totally occluded vessels had a greater hemodynamic effect (mean pulmonary artery pressure [ΔmPAP]: sessions with occlusion: -8.0%, without occlusion treated: -3.2%, p < 0.05) without an increased complication rate. Conclusions: The magnitude of clinical benefit is related to the hemodynamic effect of BPA which in turn is related to the number of segments treated and lesion severity. Patients who were post-PEA were less likely to respond to BPA.
MeSH term(s)	Angioplasty, Balloon/methods ; Cardiac Catheters ; Chronic Disease ; Female ; Follow-Up Studies ; Humans ; Hypertension, Pulmonary/etiology ; Hypertension, Pulmonary/physiopathology ; Hypertension, Pulmonary/surgery ; Male ; Middle Aged ; Pulmonary Artery/physiopathology ; Pulmonary Artery/surgery ; Pulmonary Embolism/complications ; Pulmonary Embolism/physiopathology ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Vascular Resistance/physiology
Language	English
Publishing date	2021-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1062522-7
ISSN	1557-3117 ; 1053-2498
ISSN (online)	1557-3117
ISSN	1053-2498
DOI	10.1016/j.healun.2021.06.011
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Article: A minimal clinically important difference measured by the Cambridge Pulmonary Hypertension Outcome Review for patients with idiopathic pulmonary arterial hypertension.

Bunclark, Katherine / Doughty, Natalie / Michael, Alice / Abraham, Nisha / Ali, Samantha / Cannon, John E / Sheares, Karen / Speed, Nicola / Taboada, Dolores / Toshner, Mark / Pepke-Zaba, Joanna

Pulmonary circulation

2021 Volume 11, Issue 2, Page(s) 2045894021995055

Abstract: Several patient-reported outcome measures have been developed to assess health status in pulmonary arterial hypertension. The required change in instrument scores needed, to be seen as meaningful to the individual, however remain unknown. We sought to ... ...

Abstract	Several patient-reported outcome measures have been developed to assess health status in pulmonary arterial hypertension. The required change in instrument scores needed, to be seen as meaningful to the individual, however remain unknown. We sought to identify minimal clinically important differences in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and to validate these against objective markers of functional capacity. Minimal clinically important differences were established from a discovery cohort (
Language	English
Publishing date	2021-05-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2638089-4
ISSN	2045-8940 ; 2045-8932
ISSN (online)	2045-8940
ISSN	2045-8932
DOI	10.1177/2045894021995055
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Article ; Online: The potential effects of pregnancy in a patient with idiopathic pulmonary arterial hypertension responding to calcium channel blockade.

Bostock, Samuel / Sheares, Karen / Cannon, John / Taboada, Dolores / Pepke-Zaba, Joanna / Toshner, Mark

The European respiratory journal

2017 Volume 50, Issue 6

MeSH term(s)	Adult ; Calcium Channel Blockers/therapeutic use ; Death, Sudden, Cardiac ; Fatal Outcome ; Female ; Humans ; Hypertension, Pulmonary/drug therapy ; Pregnancy ; Pregnancy Complications, Cardiovascular/drug therapy ; Pulmonary Artery/physiopathology
Chemical Substances	Calcium Channel Blockers
Language	English
Publishing date	2017-12-14
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.01141-2017
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Zs.A 2322: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 292: Show issues

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Article: Balloon pulmonary angioplasty outcomes in patients previously treated by pulmonary endarterectomy surgery are inferior to those of inoperable patients.

Kirkby, Louise C / Rodgers, Matthew S / Amaral-Almeida, Liliana / Sheares, Karen / Toshner, Mark / Bunclark, Katherine / Bartnik, Aleksandra / Taboada, Dolores / Ng, Choo / Taghavi, Fouad J / Tsui, Steven / Cannon, John E / Weir-McCall, Jonathan R / Coghlan, John G / Jenkins, David P / Pepke-Zaba, Joanna / Hoole, Stephen P

Pulmonary circulation

2023 Volume 13, Issue 3, Page(s) e12265

Abstract: Pulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual ... ...

Abstract	Pulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post-PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA-89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6-minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)-quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: ΔPVR (-27.9 ± 20.2% vs. -13.9 ± 23.9%,
Language	English
Publishing date	2023-07-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2638089-4
ISSN	2045-8940 ; 2045-8932
ISSN (online)	2045-8940
ISSN	2045-8932
DOI	10.1002/pul2.12265
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