Pulmonary Hypertension, Common in TAVR Patients, Linked to Lower Survival - TCTMD
Pulmonary Hypertension, Common in TAVR Patients, Linked to Lower Survival - TCTMD |
- Pulmonary Hypertension, Common in TAVR Patients, Linked to Lower Survival - TCTMD
- Pulmonary arterial hypertension targeted for new treatment by Sheffield scientists - EurekAlert
- 7 multisystemic diseases every physician should watch for - MD Linx
| Pulmonary Hypertension, Common in TAVR Patients, Linked to Lower Survival - TCTMD Posted: 26 Nov 2019 11:47 AM PST 
The analysis lacks the nuance, one expert says, to tease out exactly which patients with pre-interventional PH will fare poorly.LONDON, England—Patients with pulmonary hypertension (PH) undergoing TAVR for severe symptomatic aortic stenosis fare significantly worse than those without increased pre-interventional pulmonary pressures, a new analysis shows. After a mean follow-up of 31 months, patients with PH, which was defined as a mean pulmonary arterial pressure (mPAP) > 25 mm Hg, had a 60% increased risk of all-cause mortality compared with those without PH, reported Dionysios Adamopoulos, MD (Geneva University Hospital, Switzerland), last week at PCR London Valves 2019. "Pulmonary hypertension is very common in patients with aortic stenosis," said Adamopoulos. Pressure overload of the left ventricle leads to pulmonary vascular remodeling, diastolic dysfunction, and increasing filling pressures in the left atrium, which is then translated to the pulmonary circulation, he said. Past studies have shown that PH is associated with poor clinical outcomes in the general population, but the impact of pre-interventional PH in patients undergoing TAVR is not fully known, said Adamopoulos. The single-center study included 372 patients undergoing TAVR for severe symptomatic aortic stenosis (mean age 83 years), including 298 who were also evaluated with baseline right heart catheterization. Of these, 56% had PH. Patients with PH were more likely to have chronic obstructive pulmonary disease (22.6% vs 11.5%; P = 0.01), have worse heart failure symptoms (77.7% in NYHA class III/IV heart failure vs 69% of those without PH; P = 0.01), and have a lower left ventricular ejection fraction at discharge (60% vs 62%; P < 0.001). During follow-up, which was as long as 9 years, 31% of patients died. In the survival analysis, PH was a strong predictor of all-cause mortality (HR 1.60; 95% CI 1.03-2.50). After adjusting for COPD and ejection fraction at discharge, PH remained a significant predictor of all-cause death (HR 1.83; 95% CI 1.10-3.10). Despite the increased risk of mortality among patients with pre-interventional PH, Adamopoulos said the findings have had little impact on their clinical practice. "For the moment, no, because we can't really treat them any differently," he answered in response to the question from session co-moderator Rashmi Yadav, MBBS, PhD (Royal Brompton & Harefield NHS Foundation Trust, London, England). "Treatment of these patients is to change the pressure overload in the left ventricle and try to decrease the filling pressures, hoping that the normalization of the left ventricle pressure will reverse the diastolic dysfunction." In their study, Adamopoulos and colleagues have not yet looked at whether the procedure did in fact reverse diastolic dysfunction, but co-moderator Jane Hancock, MD, PhD (St. Thomas' Hospital, London, England), said such an analysis could be important for identifying PH patients with the best response to TAVR and those in whom the procedure might be futile. What About Severe PH? To TCTMD, Yadav said the binary definition of PH used in the analysis is one of the study's limitations, noting that while PH is defined as mPAP > 25 mm Hg, that is a relatively low bar. For those with PH, mild, moderate, and severe disease is typically classified as mPAP 25 to 40, 41 to 55, and > 55 mm Hg, respectively, and many TAVR patients would have some degree of increased pulmonary pressure, she said. "[We'd like to know] what happens to patients with severe pulmonary hypertension because patients with mild PH we would treat anyway," she said. "It's the severe group that we would sometimes say no to because we know that they have poor outcomes. They don't survive; they might die on the table. The real money is knowing what happens specifically to those with severe PH." Paul T.L. Chiam, MBBS (Mount Elizabeth Medical Center, Singapore), who moderated the session along with Yadav and Hancock, said the analysis is also confounded by the high prevalence of COPD in their population. These patients, whether they undergo TAVR or not, have poor long-term outcomes. For the patient with PH resulting from left-sided valvular disease, such as aortic stenosis, TAVR will also result in a decrease in pulmonary pressure, particularly in those with mild PH. Like Yadav, Chiam told TCTMD the analysis would be improved by studying which patients with PH drove the increase in mortality after TAVR, noting that the elevated risk was most likely skewed by those with moderate-to-severe PH. Mild elevations in pulmonary pressure before TAVR are unlikely to have a large clinical impact, said Chiam.  |
| Pulmonary arterial hypertension targeted for new treatment by Sheffield scientists - EurekAlert Posted: 15 Nov 2019 12:00 AM PST 
Scientists at the University of Sheffield, working in collaboration with drug and vaccine developer Kymab Ltd, Cambridge, have identified a novel antibody that has the potential to become a new treatment for pulmonary arterial hypertension (PAH). Research published today in Nature Communications (Friday 15 November 2019) from the University's Department of Infection, Immunity and Cardiovascular Disease shows that treatment with a specific antibody can reverse the process behind the development of PAH, and will now be considered for clinical development. Pulmonary arterial hypertension or PAH is a rare but fatal disease with the only cure being lung transplantation. It results in high blood within the lungs due to the constriction and overgrowth of the cells within the arteries that supply blood to the lungs. Over time this growth restricts blood flow through these vessels, putting strain on the heart and eventually causing heart failure. The study found osteoprotegerin (OPG) - which has primarily been thought to just regulate bone density - drives the process behind the growth of the cells within the blood vessel walls affected in PAH. A therapeutic human anti-OPG antibody was found to stop the progress of the disease in experimental lab rodent and cell models, and reverse the proliferation of cells which cause the arteries to thicken. Allan Lawrie, Professor of Translational Cardiopulmonary Science at the University of Sheffield, said: "Current treatments for PAH ease the symptoms by relaxing and dilating the affected blood vessels which can help extend the life expectancy for those living with PAH, but they do not stop the underlying drivers of the disease. "The great benefit of this research is the potential for this new drug to be used in conjunction with current treatments, to ease symptoms and further halt or reverse the progression of the disease." PAH is a rare disease, affecting less than 1 in 2000 people and has 'orphan disease' designation, meaning that despite smaller numbers of patients affected there is a recognised need for effective treatments to be developed. Sheffield Teaching Hospitals NHS Foundation Trust and the University of Sheffield are one of the largest specialist centres in the world for diagnosis, treatment and leading research into PAH, with this study being the first time that this particular mechanism of the disease has been targeted with a therapeutic human antibody. "The support from the Medical Research Council in collaboration with Kymab Ltd - which generated the antibody - and the British Heart Foundation to fund this research through the recently formed Donald Heath Research Programme in Sheffield is a hugely significant recognition of the importance of research in this field of medicine which aims to improve the outcome for patients suffering from PAH," added Professor Lawrie. ### The University of Sheffield With almost 29,000 of the brightest students from over 140 countries, learning alongside over 1,200 of the best academics from across the globe, the University of Sheffield is one of the world's leading universities. A member of the UK's prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teaching and research excellence across a wide range of disciplines. Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in. Sheffield is the only university to feature in The Sunday Times 100 Best Not-For-Profit Organisations to Work For 2018 and for the last eight years has been ranked in the top five UK universities for Student Satisfaction by Times Higher Education. Sheffield has six Nobel Prize winners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields. Global research partners and clients include Boeing, Rolls-Royce, Unilever, AstraZeneca, GlaxoSmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations. Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.  |
| 7 multisystemic diseases every physician should watch for - MD Linx Posted: 26 Nov 2019 10:09 AM PST [unable to retrieve full-text content]7 multisystemic diseases every physician should watch for MD Linx  |
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