Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive pulmonary vascular disease that is usually a consequence of prior acute pulmonary embolism. CTEPH usually begins with ...persistent obstruction of large and/or middle-sized pulmonary arteries by organised thrombi. Failure of thrombi to resolve may be related to abnormal fibrinolysis or underlying haematological or autoimmune disorders. It is now known that small-vessel abnormalities also contribute to haemodynamic compromise, functional impairment and disease progression in CTEPH. Small-vessel disease can occur in obstructed areas, possibly triggered by unresolved thrombotic material, and downstream from occlusions, possibly because of excessive collateral blood supply from high-pressure bronchial and systemic arteries. The molecular processes underlying small-vessel disease are not completely understood and further research is needed in this area. The degree of small-vessel disease has a substantial impact on the severity of CTEPH and postsurgical outcomes. Interventional and medical treatment of CTEPH should aim to restore normal flow distribution within the pulmonary vasculature, unload the right ventricle and prevent or treat small-vessel disease. It requires early, reliable identification of patients with CTEPH and use of optimal treatment modalities in expert centres.
Since the 1st World Symposium on Pulmonary Hypertension (WSPH) in 1973, pulmonary hypertension (PH) has been arbitrarily defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest, measured ...by right heart catheterisation. Recent data from normal subjects has shown that normal mPAP was 14.0±3.3 mmHg. Two standard deviations above this mean value would suggest mPAP >20 mmHg as above the upper limit of normal (above the 97.5th percentile). This definition is no longer arbitrary, but based on a scientific approach. However, this abnormal elevation of mPAP is not sufficient to define pulmonary vascular disease as it can be due to an increase in cardiac output or pulmonary arterial wedge pressure. Thus, this 6th WSPH Task Force proposes to include pulmonary vascular resistance ≥3 Wood Units in the definition of all forms of pre-capillary PH associated with mPAP >20 mmHg. Prospective trials are required to determine whether this PH population might benefit from specific management.Regarding clinical classification, the main Task Force changes were the inclusion in group 1 of a subgroup "pulmonary arterial hypertension (PAH) long-term responders to calcium channel blockers", due to the specific prognostic and management of these patients, and a subgroup "PAH with overt features of venous/capillaries (pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis) involvement", due to evidence suggesting a continuum between arterial, capillary and vein involvement in PAH.
The Fifth World Symposium on Pulmonary Hypertension Galiè, Nazzareno, MD; Simonneau, Gerald, MD
Journal of the American College of Cardiology,
12/2013, Letnik:
62, Številka:
25
Journal Article, Conference Proceeding
Treatment of Pulmonary Arterial Hypertension Humbert, Marc; Sitbon, Olivier; Simonneau, Gérald
The New England journal of medicine,
09/2004, Letnik:
351, Številka:
14
Journal Article
Recenzirano
Pulmonary arterial hypertension, which is characterized by vascular proliferation and remodeling of small pulmonary vessels, leads to a progressive increase in pulmonary vascular resistance and, ...ultimately, to right ventricular failure and death. Despite recent major improvements in therapy, no current treatments cure this devastating condition. This article discusses recent progress in developing treatments that prolong patients' lives and improve their quality of life.
Pulmonary arterial hypertension is characterized by vascular proliferation and remodeling of small vessels and leads to a progressive increase in pulmonary vascular resistance.
Pulmonary arterial hypertension is a disease of the small pulmonary arteries that is characterized by vascular proliferation and remodeling.
1
,
2
It results in a progressive increase in pulmonary vascular resistance and, ultimately, right ventricular failure and death. A diagnosis of primary (or idiopathic) pulmonary hypertension is made when no known risk factor is identified.
3
,
4
The diagnostic classification of pulmonary arterial hypertension is described in Table 1.
3
Despite recent major improvements in symptomatic treatments, no current treatment cures this devastating condition.
1
,
2
,
5
–
9
However, during the past 20 years, treatment options for patients with the disease have evolved to help . . .
For patients with chronic thromboembolic pulmonary hypertension (CTEPH), the current standard of care involves surgical removal of fibro-thrombotic obstructions by pulmonary endarterectomy. While ...this approach has excellent outcomes, significant proportions of patients are not eligible for surgery or suffer from persistent/recurrent pulmonary hypertension after the procedure. The availability of balloon pulmonary angioplasty and the approval of the first medical therapy for use in CTEPH have significantly improved the outlook for patients ineligible for pulmonary endarterectomy. In this comprehensive review, we discuss the latest developments in the rapidly evolving field of CTEPH. These include improvements in imaging modalities and advances in surgical and interventional techniques, which have broadened the range of patients who may benefit from such procedures. The efficacy and safety of targeted medical therapies in CTEPH patients are also discussed, particularly the encouraging data from the recent MERIT-1 trial, which demonstrated the beneficial impact of using macitentan to treat patients with inoperable CTEPH, including those on background therapy. As the treatment options for CTEPH improve, hybrid management involving more than one intervention in the same patient may become a viable option in the near future.
Since 1973 the World Symposia on Pulmonary Hypertension (WSPH) proceedings have summarised the scientific advances and future needs in this field through the efforts of multiple task forces, each ...focusing on a different aspect of pulmonary hypertension (PH) 1. The 6th WSPH comprised 124 experts, divided into 13 task forces, that began their work in January 2017 and presented their consensus opinions to an audience of 1376 participant attendees between February 27 and March 1, 2018 in Nice, France. A newly created task force dedicated to patients' perspectives, including representatives of patients' associations worldwide, was added for the 6th WSPH.
State of the art summary on diagnosis, prognosis, therapy and future perspectives of pulmonary hypertension
http://ow.ly/8MHN30mGtqs
In this trial, 261 patients with chronic thromboembolic pulmonary hypertension were assigned to placebo or to the soluble guanylate cyclase stimulator riociguat. At 16 weeks, riociguat had ...significantly improved the 6-minute walk distance and pulmonary vascular resistance.
Chronic thromboembolic pulmonary hypertension is characterized by obstruction of the pulmonary vasculature by residual organized thrombi,
1
leading to increased pulmonary vascular resistance, progressive pulmonary hypertension, and right ventricular failure.
2
,
3
Patients with chronic thromboembolic pulmonary hypertension have a poor prognosis unless they receive treatment early.
4
Pulmonary endarterectomy is the standard treatment for chronic thromboembolic pulmonary hypertension and is the only potentially curative treatment.
5
However, surgery is not an option for all patients; some patients are ineligible for surgery owing to the occlusion of distal vessels or coexisting conditions, some decline surgery, and some do not have access to expert surgical . . .
To evaluate safety and efficacy of balloon pulmonary angioplasty (BPA) in a large cohort of patients with chronic thromboembolic pulmonary hypertension (CTEPH).
From 2014 to 2017, 184 inoperable ...CTEPH patients underwent 1006 BPA sessions. Safety and efficacy during the first 21 months (initial period) were compared with those of the last 21 months (recent period). A total of 154 patients had a full evaluation after a median duration of 6.1 months.
Overall, there was a significant improvement in New York Heart Association functional class, 6-min walk distance (mean change +45 m), and a significant decrease in mean pulmonary artery pressure (PAP) and in pulmonary vascular resistance (PVR) by 26% and 43%, respectively. The percentage decreases of mean PAP and PVR were 22% and 37% in the initial period
30% and 49% in the recent period, respectively (p<0.05). The main complications included lung injury, which occurred in 9.1% of 1006 sessions (13.3% in the initial period
5.9% in the recent period; p<0.001). Per-patient multivariate analysis revealed that baseline mean PAP and the period during which BPA procedure was performed (recent
initial period) were the strongest factors related to the occurrence of lung injury. 3-year survival was 95.1%.
This study confirms that a refined BPA strategy improves short-term symptoms, exercise capacity and haemodynamics in inoperable CTEPH patients with an acceptable risk-benefit ratio. Safety and efficacy improve over time, underscoring the unavoidable learning curve for this procedure.
Introduction
Contemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate or high risk. A minority of patients achieve low risk status with ...most remaining intermediate risk. Our aim was to validate a four-stratum risk assessment approach categorising patients as low, intermediate-low, intermediate-high or high risk, as proposed by the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) investigators.
Methods
We evaluated incident patients from the French PAH Registry and applied a four-stratum risk method at baseline and at first reassessment. We applied refined cut-points for three variables: World Health Organization functional class, 6-min walk distance and N-terminal pro-brain natriuretic peptide. We used Kaplan–Meier survival analyses and Cox proportional hazards regression to assess survival according to three-stratum and four-stratum risk approaches.
Results
At baseline (n=2879), the four-stratum approach identified four distinct risk groups and performed slightly better than a three-stratum method for predicting mortality. Four-stratum model discrimination was significantly higher than the three-stratum method when applied during follow-up and refined risk categories among subgroups with idiopathic PAH, connective tissue disease-associated PAH, congenital heart disease and portopulmonary hypertension. Using the four-stratum approach, 53% of patients changed risk category from baseline compared to 39% of patients when applying the three-stratum approach. Those who achieved or maintained a low risk status had the best survival, whereas there were more nuanced differences in survival for patients who were intermediate-low and intermediate-high risk.
Conclusions
The four-stratum risk assessment method refined risk prediction, especially within the intermediate risk category of patients, performed better at predicting survival and was more sensitive to change than the three-stratum approach.
BACKGROUND:Hemodynamic variables such as cardiac index and right atrial pressure have consistently been associated with survival in pulmonary arterial hypertension (PAH) at the time of diagnosis. ...Recent studies have suggested that pulmonary arterial compliance may also predict prognosis in PAH. The prognostic importance of hemodynamic values achieved after treatment initiation is less well established.
METHODS:Our objective was to evaluate the prognostic importance of clinical and hemodynamic variables during follow-up, including pulmonary arterial compliance, after initial management in PAH. We evaluated incident patients with idiopathic, drug- and toxin-induced, or heritable PAH enrolled in the French pulmonary hypertension registry between 2006 and 2016 who had a follow-up right-sided heart catheterization (RHC). The primary outcome was death or lung transplantation. We used stepwise Cox regression and the Kaplan-Meier method to assess variables obtained at baseline and at first follow-up RHC.
RESULTS:Of 981 patients, a primary outcome occurred in 331 patients (33.7%) over a median follow-up duration of 2.8 years (interquartile range, 1.1–4.6 years). In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis. Median time to first follow-up RHC was 4.6 months (interquartile range, 3.7–7.8 months). At first follow-up RHC (n=763), New York Heart Association functional class, 6-minute walk distance, stroke volume index (SVI), and right atrial pressure were independently associated with death or lung transplantation, adjusted for age, sex, and type of PAH. Pulmonary arterial compliance did not independently predict outcomes at baseline or during follow-up. The adjusted hazard ratio for SVI was 1.28 (95% confidence interval, 1.11–1.49; P<0.01) per 10-mL/m decrease and for right atrial pressure was 1.05 (95% confidence interval, 1.02–1.09; P<0.01) per 1–mm Hg increase. Among patients who had 2 (n=355) or 3 (n=193) low-risk prognostic features at follow-up, including a cardiac index ≥2.5 L·min·m, 6-minute walk distance >440 m, and New York Heart Association class I or II functional class, lower SVI was still associated with higher rates of death or lung transplantation (P<0.01).
CONCLUSIONS:SVI and right atrial pressure were the hemodynamic variables that were independently associated with death or lung transplantation at first follow-up RHC after initial PAH treatment. These findings suggest that the SVI could be a more appropriate treatment target than cardiac index in PAH.
PDF
