Iron & Aortic Stenosis

Iron Alters Valvular Interstitial Cell Function and Is Associated With Calcification in Aortic Stenosis

Andres Laguna-Fernandez; Miguel Carracedo; Gregoire Jeanson; Edit Nagy; Per Eriksson; Giuseppina Caligiuri; Anders Franco-Cereceda; Magnus Bäck

Disclosures

Eur Heart J. 2016;37(47):3532-3535. 

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• Abstract and Introduction
• Materials and Methods
• Results
• Discussion

• References
• Sidebar

Abstract and Introduction

Abstract

Aims Aortic valve stenosis (AS) is the most common valvulopathy and is characterized by inflammation, extracellular matrix (ECM) remodelling and calcification, causing a narrowing of the valve and the consequential obstruction of the cardiac outflow. Although intraleaflet haemorrhage is associated with AS progression, the mechanisms involved are not known. The aims of this study were to identify valvular iron in relation to pathological changes associated with AS and the effects on valvular interstitial cells (VIC) in terms of iron uptake and iron-induced responses.

Methods and results Valvular iron accumulation was detected by Perls' staining on aortic valve sections and shown to increase with the extent of calcification. Furthermore, qRT–PCR analysis revealed that iron-containing valve regions exhibited increased expression of genes involved in ECM remodelling and calcification. In addition, we demonstrate that iron transporters are regulated by pathways with major impact on AS and that VIC can take up and accumulate iron, which resulted in increased proliferation and decreased elastin production.

Conclusion Iron, which may accumulate in the aortic valve by means of intraleaflet haemorrhages, can be taken up by VIC in a pro-inflammatory environment and actively contribute to VIC proliferation, ECM remodelling and calcification. These findings suggest a possible mechanism through which iron uptake by VIC may favour AS progression.

Inovare

Braile Biomédica launches transapical valve

Washington, DC - Brazilian developers of the Inovare transapical aortic valve are encouraged by the early experience with the device despite a 50% two-year mortality rate.

Here at CRT 2012, the Cardiovascular Research Technologies conference, Dr Valter Lima (Hospital São Francisco, Porto Alegre, Brazil) presented data from 93 of the 150 or so patients who have been implanted with the Inovare transcatheter aortic valve, a bovine pericardium and cobalt-chromium valve developed by Braile Biomédica.

In this initial experience with the device, 93% of the procedures—all transapical implants—were successful. Success was defined as achieving a mean valve gradient under 20 mm Hg with aortic regurgitation less than a grade 2+. The average mean valve gradient for all the patients was reduced from 43 mm Hg to 11 mm Hg after one year.

There were three deaths within 30 days. Mortality was 17% at one year and 50% at two years for the 79 patients for whom data are available. Lima explained the relatively high mortality is due to the small sample size and the severe illness of the patients. "It's self-defensive to say, but I think they were 'too-sick' patients," he said. "But still, 17% at the end of 12 months I think is acceptable. And, of course we need more data."

Lima explained that 76% of the patients treated so far were considered at high risk for valve surgery while the rest were completely inoperable. Also, 10 of the procedures so far were "valve-in-valve" implants for stenotic or regurgitant prosthetic valves. The patients' average STS score was 31.

Based on these results, Inovare earned regulatory approval in Brazil in November. It is currently available only for transapical implants, with 22F as the smallest size. The company is also developing an 18F transfemoral version, Lima said./.../

Benfluorex

Over 1300 deaths in Mediator scandal in France

FEBRUARY 9, 2012 Lisa Nainggolan

Villejuif, France - The number of deaths attributable to heart-valve insufficiency as a result of the use of benfluorex(Mediator, Servier) in France is much greater than previously thought, say two French researchers [1]. They estimate that 3100 people were hospitalized and over 1300 died due to valvular insufficiency associated with benfluorex use in the country during the period from 1976 to 2009.

And these figures are likely underestimates, say Drs Agnes Fournier (INSERM, Villejuif, France) and Mahmoud Zureik (INSERM Paris, France) in a report published online February 9, 2012 in Pharmacoepidemiology & Drug Safety.Prior guesses at the number of deaths associated with benfluorex have hovered around the 500 mark.

"Despite its similarity with the two appetite suppressants fenfluramine and dexfenfluramine, benfluorex was kept on the market for more than 30 years in France," say Fournier and Zureik. "Given the grave consequences benfluorex use has had for many people, a public investigation has been set in France to understand the reasons that have contributed to the delay in withdrawing benfluorex from the market and to stress needed reform of drug regulation."

This paper comes just a few days after investigators searched the offices of French healthcare regulator AFSSAPS(French Agency for Safety of Health Products), which is under scrutiny for allowing the sale of benfluorex in France long after it had been pulled from the market elsewhere, according to a Reuters report [2].

Benfluorex use was off-label for more than three decades in France

Benfluorex was marketed in France for more than 30 years, from 1976 to 2009, as an adjunct for the treatment of hyperlipidemia and among overweight patients with type 2 diabetes. Although it had anorexic properties, the drug was not marketed as an appetite suppressant, but it was used off-label for this purpose./.../

Echo predicts mortality in untreated aortic stenosis with normal LV function

JUNE17, 2011 | Marlene Busko

Montreal, QC - Researchers have identified four echo markers that predicted mortality in elderly patients with severe aortic stenosis but preserved LV function who did not undergo surgical valve replacement [1]. Dr Eddy Barasch (St Francis Hospital, Roslyn, NY) presented the study here at the American Society of Echocardiography (ASE) 2011 Scientific Sessions.

The four echocardiographic markers that predicted poor survival were greater left ventricle (LV) concentric remodeling, lower stroke volume, elevated LV filling pressures, and mildly elevated pulmonary artery pressure.

"Our findings may not be generalizable, but they suggest that in [elderly, symptomatic patients with untreated aortic stenosis] with normal LV function, no other valve disease, and normal sinus rhythm, these echocardiographic parameters may be useful for risk stratification," Barasch told heartwire. Being able to predict mortality with surgery vs medical therapy in patients such as these—who are typical of patients seen in clinical practice—will become even more important when transcatheter aortic-valve implantation (TAVI) becomes available, he added.

The data suggest that "not operating on symptomatic patients like this—with these markers—is really a death sentence," said Dr Malissa Wood (Massachusetts General Hospital Heart Center, Boston), when asked to comment on the study."When you are managing patients who may in fact be good candidates for surgery, looking at their echo and figuring out if they have these risk factors can help determine the patients' overall risk of mortality with surgery vs medical therapy," she added./.../

New safety, durability data for percutaneous mitral-valve repair system

AUGUST 14, 2009 | Shelley Wood

Washington, DC - New safety and durability data for the percutaneous MitraClip system (Evalve), an experimental device being tested for the treatment of mitral regurgitation, suggest that the device yields lasting improvements in mitral regurgitation, with at least two-thirds of patients treated surviving out beyond one year, without needing mitral-valve surgery or developing worsening mitral regurgitation [1]. Of the patients who ended up needing valve repair, there appeared to be no downsides to first having been treated with the device, investigators said.

The MitraClip [Source: Evalve]
"Surgical options were preserved," the authors, led by Dr Ted Feldman (Evanston Hospital, IL), write in the August 18, 2009 issue of the Journal of the American College of Cardiology.

The new data come from 107 patients treated as part of the nonrandomized EVEREST 1 and 2 studies. Results for both studies have previously been reported by heartwire, but the current paper includes larger numbers and additional details and follow-up. The device itself emulates the edge-to-edge repair technique pioneered surgically by Dr Ottavio Alfieri, in which the free edge of the anterior mitral-valve leaflet is joined to the posterior leaflet, creating a point of permanent coaptation and a double orifice./.../

Is prophylaxis for endocarditis essential, or just a habit that's hard to break?

Is prophylaxis for endocarditis essential, or just a habit that's hard to break?

OCTOBER 17, 2008 | Lisa Nainggolan

Oxford, UK - The issue of when, or even if, antibiotics should be given for the prevention of infective endocarditis (IE) has been the subject of much debate recently, with three clear schools of thought emerging. These have resulted in varying guidance from different organizations and countries, leading to much confusion.

For more than 50 years, in most Western countries, the administration of antibiotics as prophylaxis to those individuals at high risk of developing endocarditis has been routine before dental and other invasive surgical procedures. But at the beginning of this decade, scientists started to see a shift in the clinical and microbiologic profile of the disease, which led some to question whether the traditional practice of prophylaxis for all patients at risk should continue. Beginning a few years ago, certain organizations started to alter their recommendations, leading to the current situation./.../

Management of Patients With Valvular Heart Disease:

2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease)

Robert O. Bonow MD