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Archive for the ‘cardiology & cardiac surgery’ Category

From Reuters business pages comes news of the latest ‘non-inferiority’ trial from medical equipment mega-giants, Medtronic.  They are using the occasion to push the TAVI valve for ‘intermediate risk’ patients with aortic stenosis.

Who is intermediate risk?  Well, when it comes to people with aortic stenosis – the case can be made – just about everyone.

So what’s my bias – you ask?  The same as always – the slick talking and flexible result reporting behind ‘non-inferiority’ trials and their trial designs.  We talked about this data manipulation before – during another discussion of cardiology studies – the stent versus CABG studies (Syntax trial).

Want to know more about non-inferiority trials and study designs?

Snappin has an excellent article describing this research design here.

More on non-inferiority trials by Schumi & Wittes

“By contrast, non-inferiority trials tend to reward the careless. The less rigorously conducted the trial, the easier it can be to show non-inferiority. As treatments improve, showing benefit of a new therapy becomes more and more difficult, but showing non-inferiority becomes ever easier, stemming from ‘lack of constancy’ (deliciously termed ‘biocreep’ in drugs and ‘technocreep’ in devices).”

Here’s another explanation that’s a little less technical..

“Non-inferiority really means “not too inferior”, and how inferior is too inferior must be determined. You should plan on plenty of pre-protocol discussion over this topic.” – Nancy Stark

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A frightening decision by the FDA just as a savvy reader forwarded an episode of last season’s Grey’s Anatomy – which highlights the issues involved in the use of TAVI.   In this article, “FDA extends Sapien use to high-risk surgical patients“, Shelly Wood at the heart.org explains the FDA’s recent decision to expand eligibility criteria for TAVI use to patients eligible for surgery, (but deemed high risk).  No mention is made of the recent controversy over TAVI due to higher than expected complications.

At the same time, a reader encouraged me to watch last season’s Grey’s Anatomy episode where a low-risk patient demands (and RECEIVES) TAVI instead of traditional surgery because he doesn’t want a scar to mar his physique.  Of course, there is no mention on the show of post-procedural complications (because it’s a fictional program on television) but the very manner in which the episode was handled is frightening.

There was no discussion of unnecessary risk for the patient using experimental technology, or of the Major vascular complications that occur in more than one in seven TAVR patients: according the PARTNER trial.  There is also no mention of the drastic increase in mortality if these complications occur.  In the episode, the resident researches the procedure – and decides (appropriately) that the procedure is not suitable for the patient.  He is then scooped by the cardiac surgeon, who decides, “hey – what the heck – seize the day!”

Link to clip of Grey’s Anatomy

But as I said – it’s only television, right?  Except that it isn’t.  It’s a powerful medium used to disseminate information to the millions of people who watch that program.  (9.5 million people, according to recent ratings information.)  They also make a pretty huge leap on the program – changing TAVI from a procedure supposedly for patients with no other option (surgery ineligible) to a low-risk patient who wants to avoid a scar..

and now – the FDA expands criteria – despite a turbulent summer which included  previous criticism (by the FDA) based on irregularities in the PARTNER trial itself – and a violent controversy over the safety of this procedure.  The British Medical Journal also published an article over the summer decrying the overuse of the procedure.

Additional References – more in archives

1.  Amabile N, Azmoun A, Ghostine S, Ramadan R, Haddouche Y, Raoux F, To NT, Troussier X, Nottin R, Caussin C. (2012).  Incidence, predictors and prognostic value of serious hemorrhagic complications following transcatheter aortic valve implantation. Int J Cardiol. (2012 Oct 15). pii: S0167-5273(12)01131-X. doi: 10.1016/j.ijcard.2012.09.025. [Epub ahead of print]

Since the article is not available – I have included the abstract.

Abstract

BACKGROUND:

TAVI is an alternative solution for patients with aortic valve stenosis (AS) who are refused for conventional surgery. We sought to evaluate the incidence, characteristics, predictors and prognosis impact of serious hemorrhagic complications following transcatheter aortic valve implantation (TAVI).

METHODS:

One hundred and seventy-one consecutive patients with symptomatic severe AS (83.5±6.1y; 53% women; mean EuroSCORE=22.1±12.3) underwent transapical (TA) or transfemoral (TF) TAVI in our institution using Edwards SAPIEN© and Medtronic CoreValve© devices. The primary evaluated criterion was the incidence of any bleeding complication, according to the Valve Academic Research Consortium (VARC) criteria.

RESULTS:

VARC serious hemorrhagic complications occurred in 34.5% of patients (n=23 life-threatening/disabling (LT/D) and n=36 major bleedings). Most of these complications were related to access site complications (69%). Multivariable analysis revealed that TA access, low weight and underlying coronary artery diseases were independent predictors for development of serious bleeding. The mortality was significantly higher in patients with serious events compared to patients without bleeding (p=0.008, log-rank analysis). Although the survival didn’t significantly differ in patients with major hemorrhagic events, subjects with LT/D bleeding events had a higher mortality than the subjects with no hemorrhagic complications (p<0.001, log-rank analysis). Occurrence of VARC LT/D event independently predicted all-cause mortality (HR=5.35 [2.51-11.43], p<0.001) during the first year following TAVI in multivariate Cox regression analysis.

CONCLUSION:

Severe bleeding is frequent following TAVI procedure and is mainly related to local hemorrhage. VARC LT/D events are associated with decreased survival after AS correction.

2.  Gul M, Erkanli K, Erol MK, Bakir I. (2012).  Ventricular Embolization of Edwards SAPIEN Prosthesis Following Transcatheter Aortic Valve Implantation.  J Invasive Cardiol. 2012 Oct;24(10):537-8.  While this is a single case, this illustrates much of the data presented in a previous post.

3.  Latsios G, Toutouzas K, Tousoulis D, Stathogiannis K, Tentolouris C, Synetos A, Filis K, Stefanadis C.  (2012).   Prosthetic aortic valve removal from the abdominal aorta after successful “valve-through” TAVI.  Int J Cardiol. 2012 Oct 12. pii: S0167-5273(12)01285-5. doi: 10.1016/j.ijcard.2012.09.164. [Epub ahead of print]
Given that the patient almost lost his leg (and was taken to the operating room for emergency limb salvage surgery with a vascular surgeon), I think ‘success’ is a bit presumptuous for the title.  Reminds me of an old medical joke around the hospital when I was in training (which I have made some adjustments to.)
Dr. [exhultant as he leaves the cath lab] “I successfully implanted the new TAVI valve.”
Nurse:  But doctor, the patient died twenty minutes ago, [as she covers wheels corpse out of cath lab.]
Want more information on TAVI and aortic stenosis?  Just look in our archives.

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Heading out-of-town for a conference for a few days – but in the meantime, I’ll be working one several case reports from recent surgeries.

We will also be talking about the latest stories from the Heart.org about the recent rise in off-label use of dabigatran (Pradaxa) use.

Rise in Pradaxa (dabigatran) linked to off-label use

Off-label uses

While this new anti-coagulant has been touted as the ‘easy’ alternative to warfarin since serum monitoring is not required – it is currently approved for the use of non-valvular atrial fibrillation only in the United States.

While it is approved for deep vein thrombosis prevention (DVT prophylaxis) in Europe – it is not, and should not be used for anti-coagulation in patients with mechanical valves.  

Off-label use in Canada leads to life-threatening complications

However, that is apparently exactly how doctors in Canada have been using it – with life-threatening consequences.  In a separate article at the Heart.org, doctors report that two female patients with mechanical valves who were recently switched from warfarin to dabigitran suffered from valvular thrombosis.

The “easy button” strikes again

More concerning, these patients had previously been successfully managed on warfarin without problems prior to the switch.  (So they were taken off a drug that was working well – and switched to a drug that is not approved for this condition because it was perceived to be easier to use.)

Within one month of the switch both patients began experiencing symptoms and were then diagnosed with valvular thrombosis.  Fortunately, neither of these patients died – but they certainly could have.

My former boss had a saying, “the enemy of good is better” meaning that if we try too hard to improve on something that is already working  – we unnecessary risk the lives and health of our patients.

Anticoagulants are not all the same

This just brings home the message that drugs that may seem similar, aren’t.  The way that dabigatran works is very different that warfarin, aspirin, clopidogrel (Plavix), abciximab (Reopro) or the other myriad of anti-coagulation type drugs.  Some of these drugs work on platelets – some of these drugs work on different parts of a complex mechanisms of coagulation (the coagulation cascade).   ‘Anti-coagulants’ is just a blanket term for these medications – and certainly doesn’t fully cover the intricacies of the pharmacology involved.  ‘Easy’ it isn’t – but medicine rarely is.

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Long time readers (and former patients) will be familiar with my aspirin mantra but now Medscape has published a CME course by Dr. Desiree Lie for health care providers in primary practice, general surgery (and other areas that may not be familiar with post-cardiac patient recommendations.)  As I may have mentioned before, in cardiac surgery – we routinely start aspirin in our patients prior to bypass surgery.

Don’t stop Aspirin before surgery

I’ve converted the CME course, Don’t stop Aspirin before surgery into a pdf – but if you want credit – you will have to go to Medscape and log in.  (For everyone else – it’s a nice read – and explains the importance of continuing aspirin in patients who are taking it for “secondary prevention” or are at high risk of cardiovascular events.

That’s because the complications of discontinuing aspirin therapy in these patients are WORSE than the minor risk of bleeding.  (Bleeding issues for most patients taking aspirin are fairly minor.. Now, clopidogrel (Plavix) and prasugrel (Effient) are another story!)

Wait a second… What’s secondary prevention?

They way to think about secondary prevention is “closing the barn after the cows are loose,” as one of my colleagues explains it.  This means that Aspirin has been prescribed to these patients after something has already happened – like a stroke, a heart attack, stents or cardiac surgery.  So in these patients – secondary prevention can be thought of as preventing a second event or further complications from a disease process we already know about.

Now, patients that are at high risk for cardiovascular events like diabetics or people with other kinds of blockages (peripheral vascular disease, renal artery stenosis) haven’t had a heart attack yet – but we think that they are at a high risk of this happening – so they take aspirin to prevent this (primary prevention).

In people who are at low or moderate risk – low cholesterol, nonobese, normal glucose, nonsmokers:  these people may take aspirin, but (probably not prescribed) and it is safe for them to discontinue aspirin before surgery.

But in the first two classes of patients (secondary prevention group/ high risk group) – stopping aspirin may actually INCREASE the risk of having a heart attack, stroke or other thrombotic event during surgery.  But if you are having surgery – be sure to check with your cardiologist or cardiac surgeon before.  Don’t rely on your PCP or general surgeon (it’s not their area of expertise) and they may not be up-to-date on the latest recommendations [hence the continuing education course].

A new chapter at Cartagena Surgery: the DNP program

Nashville, Tennessee

Back in Mexicali, MX after spending a week in Nashville, Tennessee for the start of my doctoral program in nursing.  It felt weird to be back in Nashville after so long (I lived there while attending Vanderbilt for my masters degree).  It was surprising how much had changed – the medical center and the university campus just continue to grow and grow!

But then again – with 70 people in the Fall 2012 DNP class, I guess it’s no surprise that the campus is growing.  About 15 of us are full-time students.  I’ll be heading off to Bogotá in a week to start some specialized study there – so between the DNP program and Bogotá – I might be posting a bit less often.

Fall 2012 class for DNP (doctorate of nursing practice) at Vanderbilt University

The DNP is a new degree that takes the place of the DNSc (doctorate of nursing science) or the ND (nursing doctorate) – depending on who you ask.  I know that sounds like alphabet soup to many people, so I’ll post some more information about the degree soon.  But the main thing to think about when thinking about doctoral degrees – is the focus behind the degree.

PhD – or a doctorate in Philosophy are Research degrees. (research with a capital ‘R’)  Think about labs, nursing theories and hard-core research..so think ‘nurse-scientists’.. I tell people to picture a nurse with a beaker and a bunsen burner.. Not entirely accurate but a good mental picture.

DNP – is a clinical doctorate – used to translate much of this research into improved clinical practice.  Clinical, clinical, clinical.. This is the degree for people who are still planning on working in the clinical (hospital-based or clinic-based) setting, seeing patients.  The courses in this program are designed to promote evidence-based practice – or using all of that research that our nurse-scientists (and other researchers) are publishing.

So the hope is that the DNP will be able to improve the care of patients by creating protocols and such.  As it is still a fairly new degree – there is currently a lot of cross-over among PhD trained nurses, and I suspect there always will be – it’s more a matter of preference in what a nurse wants to focus on during her doctorate education. (So don’t be surprised if your nurse practitioner has a PhD.)

There are still plenty of doctorates in education and other fields as well like administration because it takes all types of nurses to serve as faculty, deans of educational programs, and hospital administrators.

There are even a few doctorate of nursing science programs left – in Louisiana and Puerto Rico..

Now I apologize because this is a simplistic explanation that leaves out a lot of nuance but I’ll provide more information soon.  But now, I better get back to the books!

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It looks like the rest of the medical community is finally speaking up about the overuse and safety issues of TAVI/ TAVR for aortic stenosis, but it’s still few and far between – and in specialty journals…  But in the same week that Medscape, and the Heart.org reported on a newly published article in the British Medical Journal on the overuse of TAVI therapies, and the need for earlier diagnosis and treatment of Aortic Stenosis – the Interventionalists over at the Heart.org (a cardiology specialty journal)  have published a series of articles promoting / pushing the procedure including an article entitled, “The TAVR Heart team roles.”

JAMA recently published a paper by Robert Bonow and Chintan Desnai, discussing the benefits, risks and expectations with TAVI.  This paper discusses the very real need for clinicians to address heightened patient expectations regarding TAVI as an ‘easy’ alternative to surgery.

TAVI is vastly overused – Reed Miller, The Heart.org

Here at Cartagena Surgery – we’ve been doing our own research – contacting and talking to a multitude of practicing cardiologists and cardiac surgeons to get their opinions – in addition to reviewing the latest data.

In related news, a review of the latest research on the ‘transcatheter’ valve therapies demonstrates considerable concern: including data on peri-valvular leaks as reported in the last national TAVI registries in Europe and in the US:

The incidence of  paravalvular leaks  after TAVI is extremely high  ( > 60%)

• It is technically challenging today to quantify these leaks.

• Most of them are quoted “mild”, but more than 15 % are estimated  “moderate” and “severe”.

• In > 5% of patients, the peri-valvular or valvular regurgitation grade increased significantly over time.

• there is no significant difference between Edwards SAPIEN and Medtronic COREVALVE

As one cardiologist explained:

“Importantly, the thrombogenic potential of mild leaks was recently demonstrated by Larry Scotten ( Vivitro System Inc. Victoria, Canada). High reverse flow velocities expose glycoprotein GP Ib-IX-V  platelet receptors  to circulating Von Willebrand molecule with, as results, platelet aggregation and fibrin formation.  The incidence of brain spots and stroke after TAVI was of great concern in the PARTNER A and B studies.  Whereas, Aspirin is not mandatory  in  patients implanted with bioprosthetic valves,   Plavix +  Aspirin is recommended for all TAVI patients. The rationales of such therapy were not explained so far.”

Valve oversizing – a surgeon explains

“To reduce  these peri-valvular leaks , cardiologists tentatively use large valve size, up to 29-mm.  The very large majority of valve sizes used in conventional aortic valve replacement are smaller than 25-mm.  Oversizing may increase the risk of late aortic aneurysms (aortic rupture has been reported) [emphasis added].

Moreover, atrio-ventricular conduction may be impaired  with the need of permanent pacing. Poorer outcomes have been reported in patients when the need for permanent pacemaker occurs.

“As we like to say about clothes and shoes, you forget the price overnight but you remember the quality for ever . The price of TAVI may be cheaper but patients may experience inferior outcomes. In view of these results, using TAVI would not be appropriate for the great majority of  heart valve candidates.  Moreover trans-catheter delivery and sub-optimal fit are not likely to increase tissue valve durability…  and everybody knows that tissue valves are not enough durable for young adults and children.  TAVI is thus a suitable strategy only for the neglected population of high risk patients who are no longer candidates for surgery [emphasis added].

Worth pointing out again  that there would be no need for TAVI and long-term outcomes of patients would be much better if severe aortic stenosis were correctly managed at the right time.  Enclosed the recommendations of Robert Bonow   (Circulation, July 25, 2012) for early valve replacement in ASYMPTOMATIC  patients.  A large cohort of accurate biomarkers is available today for correct timing of surgery  and consequent prevention of  irreversible myocardium damage. In the study of Lancellotti (enclosed) 55% of “truly asymptomatic patients” with severe aortic stenosis developed pulmonary hypertension during exercise and had  poor clinical outcomes. The measurement of both mean trans-aortic pressure gradient and systolic pulmonary pressure, which are technically easy, rapid and with good reproducibility may improve the management of such patients.

These updates on the natural history of aortic stenosis illustrate the present paradoxical and intriguing  focus of the industry on an experimental procedural innovation for end-stage old patients when more efficient heart valves are today feasible and could be used sooner for the benefit of all patients .

Enclosed an article on The Need For A Global Perspective On Heart Valve from Sir Madgi Yacoub.

Additional Reference / supporting data:

Modified from  Ross J and Branwald E   (Circulation 1968 (Suppl): 61-67)

• The  incidence of stroke was 9% after TAVI in  the 214 patients of the enclosed study published last week in the American Journal of Cardiology. The incidence of stroke with TAVI was >  two times higher than with conventional surgery in the PARTNER study.  Pooled proportion of postoperative stroke was 2.4%  with conventional surgery  in the  large meta-analysis of patients > 80 years old (enclosed)

• Peri-valvular aortic insufficiency is observed in more than  60% of patients undergoing trans-catheter aortic valve replacement.  Moderate or severe aortic insufficiency was seen in 17.3 % of the PARTNER inoperable and high risk cohorts at 1 year.  They have been reportedly associated with dyspnea, anemia,  cardiac failure and diminished survival. Most interestingly,  the FDA does not accept more than  1%   peri-valvular insufficiency in patients implanted with conventional prosthetic heart valves… The SJM Silzone mechanical heart valve was re-called  because of peri-valvular leakage rate of…  1.5 % .

• Traditionally, aortic stenosis involving a 2-cuspid aortic valve has been a contraindication to TAVI.  Of 347 octogenarians and 17 nonagenarians  explanted valves , 78 (22%) and 3 ( 18%) had stenotic congenitally bicuspid aortic valve, respectively.  Because the results of TAVI are less favorable in patients with stenotic congenitally bicuspid valves, proper identification of the underlying aortic valve structure is critical when considering TAVI in older patients . More than 50% of patients with aortic stenosis have bicuspid aortic valve and are not, therefore,  good candidates for TAVI. Most importantly, the great majority of patients with calcified stenotic  bicuspid aortic valves is  young ( < 60 years old)  and not candidate for tissue valve replacement.

•  The French Registry of trans-catheter aortic-valve implantation in high-risk patients was published in the New England Journal of Medicine on May 3,  2012. It reports  3195 TAVI procedures during the last two years at 34 centers.

The mean age was 83 years.  The incidence of stroke was 4.1%.  Peri-prosthetic aortic regurgitation was 64 %. The rate of death was 24% at one year. At the same time, the meta-analysis published in the American Heart Journal reports 13,216     CONVENTIONAL AORTIC VALVE REPLACEMENT in patients > 80 years old.    The rate of death was 12.4%  at one year,   21.3%  at 3 years and  34.6%  at 5 years

 

Full references for works cited in text:

Bonow, R. O. (2012). Exercise hemodynamics and risk assessment in asymptomatic aortic stenosisCirculation 2012, July 25.

Lancelloti, P., Magne, J., Donal, E., O’Connor, K., Dulgheru, R., Rosca, M., & Pierard, L. (2012).  Determinants and prognostic significance of exercise pulmonary hypertension in asymptomatic severe aortic stenosis.  Circulation, 2012 July 25.

Takkenberg, J. J. M., Rayamannan, N. M., Rosenhek, R., Kumar, A. S., Carapitis, J. R., & Yacoub, M. H. (2008).  The need for a global perspective on heart valve disease epidemiology: The SHVG working group on epidemiology of heart disease founding statement.  J. Heart Valve Dis. 17 (1); 135 – 139.

Gilard M, Eltchaninoff H, Iung B, Donzeau-Gouge P, Chevreul K, Fajadet J, Leprince P, Leguerrier A, Lievre M, Prat A,Teiger E, Lefevre T, Himbert D, Tchetche D, Carrié D, Albat B, Cribier A, Rioufol G, Sudre A, Blanchard D, Collet F, Dos Santos P, Meneveau N, Tirouvanziam A, Caussin C, Guyon P, Boschat J, Le Breton H, Collart F, Houel R, Delpine S,Souteyrand G, Favereau X, Ohlmann P, Doisy V, Grollier G, Gommeaux A, Claudel JP, Bourlon F, Bertrand B, Van Belle E, Laskar M; FRANCE 2 Investigators. Collaborators (184). Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med. 2012 May 3; 366(18):1705-15 [full abstract below].

BACKGROUND:

Transcatheter aortic-valve implantation (TAVI) is an emerging intervention for the treatment of high-risk patients with severe aortic stenosis and coexisting illnesses.

We report the results of a prospective multicenter study of the French national transcatheter aortic-valve implantation registry, FRANCE 2.

METHODS:

All TAVIs performed in France, as listed in the FRANCE 2 registry, were prospectively included in the study. The primary end point was death from any cause.

RESULTS:

A total of 3195 patients were enrolled between January 2010 and October 2011 at 34 centers. The mean (±SD) age was 82.7±7.2 years; 49% of the patients were women.

All patients were highly symptomatic and were at high surgical risk for aortic-valve replacement. Edwards SAPIEN and Medtronic CoreValve devices were implanted in 66.9% and 33.1% of patients, respectively. Approaches were either transarterial (transfemoral, 74.6%; subclavian, 5.8%; and other, 1.8%) or transapical (17.8%).

The procedural success rate was 96.9%. Rates of death at 30 days and 1 year were 9.7% and 24.0%, respectively.

At 1 year, the incidence of stroke was 4.1%, and   the incidence of periprosthetic aortic regurgitation was 64.5%.

In a multivariate model, a higher logistic risk score on the European System for Cardiac Operative Risk Evaluation (EuroSCORE), New York Heart Association functional class III or IV symptoms, the use of a transapical TAVI approach, and a higher amount of periprosthetic regurgitation were significantly associated with reduced survival.

CONCLUSIONS:

This prospective registry study reflected real-life TAVI experience in high-risk elderly patients with aortic stenosis, in whom TAVI appeared to be a reasonable option.

Rutger-Jan Nuis, MSc,  Nicolas M. Van Mieghem, MD,  Carl J. Schultz, MD, PhD,  Adriaan Moelker, MD, PhD ,  Robert M. van der Boon, MSc, Robert Jan van Geuns, MD, PhD, Aad van der Lugt, MD, PhD,  Patrick W. Serruys, MD, PhD, Josep Rodés-Cabau, MD,  Ron T. van Domburg, PhD,  Peter J. Koudstaal, MD, PhD,  Peter P. de Jaegere, MD, PhD.  Frequency and Causes of Stroke During or After Trans-catheter Aortic Valve Implantation. American Journal of Cardiology Volume 109, Issue 11 , Pages 1637-1643, 1 June 2012 [full abstract provided].

Transcatheter aortic valve implantation (TAVI) is invariably associated with the risk of clinically manifest transient or irreversible neurologic impairment. We sought to investigate the incidence and causes of clinically manifest stroke during TAVI. A total of 214 consecutive patients underwent TAVI with the Medtronic-CoreValve System from November 2005 to September 2011 at our institution. Stroke was defined according to the Valve Academic Research Consortium recommendations. Its cause was established by analyzing the point of onset of symptoms, correlating the symptoms with the computed tomography-detected defects in the brain, and analyzing the presence of potential coexisting causes of stroke, in addition to a multivariate analysis to determine the independent predictors.  Stroke occurred in 19 patients (9%) and was major in 10 (5%), minor in 3 (1%), and transient (transient ischemic attack) in 6 (3%). The onset of symptoms was early (≤24 hours) in 8 patients (42%) and delayed (>24 hours) in 11 (58%). Brain computed tomography showed a cortical infarct in 8 patients (42%), a lacunar infarct in 5 (26%), hemorrhage in 1 (5%), and no abnormalities in 5 (26%). Independent determinants of stroke were new-onset atrial fibrillation after TAVI (odds ratio 4.4, 95% confidence interval 1.2 to 15.6), and baseline aortic regurgitation grade III or greater (odds ratio 3.2, 95% confidence interval 1.1 to 9.3).

In conclusion, the incidence of stroke was 9%, of which >1/2 occurred >24 hours after the procedure. New-onset atrial fibrillation was associated with a 4.4-fold increased risk of stroke. In conclusion, these findings indicate that improvements in postoperative care after TAVI are equally, if not more, important for the reduction of peri-procedural stroke than preventive measures during the procedure.

Sinning JM, Hammerstingl C, Vasa-Nicotera M, Adenauer V, Lema Cachiguango SJ, Scheer AC, Hausen S, Sedaghat A, Ghanem A, Müller C, Grube E,Nickenig G, Werner N. (2012).  Aortic regurgitation index defines severity of peri-prosthetic regurgitation and predicts outcome in patients after transcatheter aortic valve implantation.  J Am Coll Cardiol. 2012 Mar 27;59(13):1134-41. [full abstract provided].

OBJECTIVES:

The aim of this study was to provide a simple, reproducible, and point-of-care assessment of peri-prosthetic aortic regurgitation (periAR) during trans-catheter aortic valve implantation (TAVI) and to decipher the impact of this peri-procedural parameter on outcome.

BACKGROUND:

Because periAR after TAVI might be associated with adverse outcome, precise quantification of periAR is of paramount importance but remains technically challenging.

METHODS:

The severity of periAR was prospectively evaluated in 146 patients treated with the Medtronic CoreValve (Minneapolis, Minnesota) prosthesis by echocardiography, angiography, and measurement of the aortic regurgitation (AR) index, which is calculated as ratio of the gradient between diastolic blood pressure (DBP) and left ventricular end-diastolic pressure (LVEDP) to systolic blood pressure (SBP): [(DBP – LVEDP)/SBP] × 100.

RESULTS:

After TAVI, 53 patients (36.3%) showed no signs of periAR and 71 patients (48.6%) showed only mild periAR, whereas 18 patients (12.3%) and 4 patients (2.7%) suffered from moderate and severe periAR, respectively. The AR index decreased stepwise from 31.7 ± 10.4 in patients without periAR, to 28.0 ± 8.5 with mild periAR, 19.6 ± 7.6 with moderate periAR, and 7.6 ± 2.6 with severe periAR (p < 0.001), respectively. Patients with AR index <25 had a significantly increased 1-year mortality risk compared with patients with AR index ≥25 (46.0% vs. 16.7%; p < 0.001). The AR index provided additional prognostic information beyond the echocardiographically assessed severity of periAR and independently predicted 1-year mortality (hazard ratio: 2.9, 95% confidence interval: 1.3 to 6.4; p = 0.009).

CONCLUSIONS:

The assessment of the AR index allows a precise judgment of periAR, independently predicts 1-year mortality after TAVI, and provides additional prognostic information that is complementary to the echocardiographically assessed severity of periAR.

Gotzmann M, Lindstaedt M, Mügge A. (2012). From pressure overload to volume overload: Aortic regurgitation after transcatheter aortic valve implantation.  Am Heart J. 2012 Jun;163(6):903-11.  [full abstract provided].

Severe aortic valve stenosis is a common valvular heart disease that is characterized by left ventricular (LV) pressure overload. A lasting effect of pressure overload is LV remodeling, accompanied by concentric hypertrophy and  increased   myocardial stiffness. Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement for patients with severe symptomatic aortic valve stenosis and high surgical risk.   Although TAVI has  favorable hemodynamic performance, aortic valve regurgitation (AR) is the most frequent complication because of the specific technique used for implantation of transcatheter valves.

During  implantation, the calcified native valve is pushed aside, and the prosthesis usually achieves only an incomplete prosthesis apposition. As a consequence, the reported prevalence of moderate and severe AR after TAVI is  6% to 21%,  which is considerably higher than that after a surgical valve replacement. Although mild AR probably has minor hemodynamic effects, even moderate AR might result in serious consequences. In moderate and   severe  AR  after TAVI,  a normal-sized LV with increased myocardial stiffness has been exposed to volume overload. Because the noncompliant LV is unable to raise end-diastolic volume, the end-diastolic pressure increases, and  the  forward stroke volume    decreases. In recent years, an increasing number of patients have successfully undergone TAVI. Despite encouraging overall results, a substantial number of patients receive neither symptomatic nor prognostic benefits from TAVI.   Aortic valve regurgitation has been considered a potential contributor to morbidity and mortality after TAVI. Therefore, various strategies and improvements in valve designs are mandatory to  reduce the prevalence of AR after TAVI.

Walther T , Thielmann M, Kempfert J, Schroefel H, Wimmer-Greinecker G, Treede H, Wahlers T, Wendler O. (2012). PREVAIL TRANSAPICAL: multicentre trial of transcatheter aortic valve implantation using the newly designed bioprosthesis (SAPIEN-XT) and delivery system (ASCENDRA-II).  Eur J Cardiothorac Surg. 2012 Aug;42(2):278-83. Epub 2012 Jan 30.  [full abstract provided].

OBJECTIVE

Transapical (TA- aortic valve implantation (AVI) has evolved as an alternative procedure for high-risk patients.  We evaluated the second-generation SAPIEN xt ™ prosthesis in a prospective multicentre clinical trial.

METHODS

A total of 150 patients  (age : 81.6;  40.7 % female) were included. Prosthetic valves (diameter :23 mm (n= 36), 26 mm (n= 57) and 29 mm (n= 57) were implanted. The ASCENDRA-II™ modified delivery system was used in the smaller sizes.   Mean logistic EuroSCORE was  24.3%  and mean STS score was 7.5 ± 4.4%.  All patients gave written informed consent.

RESULTS:

Off-pump AVI was performed using femoral arterial and venous access as a safety net.  All but two patients receivec TA-AVI, as planned.  The 29-mm valve showed similar function as the values of two other diameters did.  Three patients (2%) required temporary bypass support.

Postoperative complications included renal failure requiring long-term dialysis in four, bleeding requiring re-thoracotomy in four, respiratory complication requiring re-intubation in eight and septsis in four patients, respectively.

Thirty day mortality was 13 ( 8.7%)  for the total cohort and 2/57  (3.5%) receiving the 29 mm valve respectively.   Echocardiography at discharge showed none or trivial incompetence (AI) in  71%  and mild-AI in 22% of the patients.  Post-implantation AI was predominantly para-valvular and > 2+  in 7% of patients.  One patient required re-operation for AI within 30 days.

CONCLUSION

The PREVAIL TA multicenter trial demonstrates good functionality and good outcomes for TA-AVI, using the SAPIEN xt ™ and its second generation ASCENDRA-II™ delivery system, as well successful  introduction of the 29-mm  SAPIEN XT ™ valve for the benefit of high-risk elderly patients.

Subramanian S, Rastan AJ, Holzhey D, Haensig M, Kempfert J, Borger MA, Walther T, Mohr FW. (2012).  Conventional Aortic Valve Replacement in Transcatheter Aortic Valve Implantation Candidates: A 5-Year ExperienceAnn Thorac Surg.   July 19 2012  [full abstract provided].

BACKGROUND:

Patient selection for transcatheter aortic valve implantation (TAVI) remains highly controversial. Some screened patients subsequently undergo conventional aortic valve replacement (AVR) because they are unsuitable TAVI candidates. This study examined the indications and outcomes for these patients, thereby determining the efficacy of the screening process.

METHODS:

Between January 2006 and December 2010, 79 consecutive patients (49% men), aged older than 75 years with high surgical risk, were screened for TAVI, but subsequently underwent conventional AVR through a partial or complete sternotomy. The indications, demographics, and outcomes of this cohort were studied.

RESULTS:

Mean age was 80.4 ± 3.6 years. Mean left ventricular ejection fraction was 0.55 ± 0.16, and the mean logistic European System for Cardiac Operative Risk Evaluation was 13% ± 7%. Of the 79 patients, 6 (7.6%) had prior cardiac surgical procedures. Indications for TAVI denial after patient evaluations were a large annulus in 31 (39%), acceptable risk profile for AVR in 24 (30%), need for urgent operation in 11 (14%), and concomitant cardiovascular pathology in 5 (6%). Mean cross-clamp time was 55 ± 14 minutes, and cardiopulmonary bypass time was 81 ± 21 minutes. Concomitant procedures included a Maze in 12 patients (15%). Postoperative morbidity included permanent stroke in 2 (2.5%), respiratory failure in 9 (11%), and pacemaker implantation in 2 (2.5%). Hospital mortality was 1.3% (1 of 79). Cumulative survival at 6, 12, and 36 months was 88.5%, 87.1% and 72.7%, respectively.

CONCLUSIONS:

Our existing patient evaluation process accurately defines an acceptable risk cohort for conventional AVR. The late mortality rate reflects the advanced age and comorbidities of this cohort. The data suggest that overzealous widening of TAVI inclusion criteria may be inappropriate.

Industry fights back

Now it looks like Edwards Lifesciences,  the company that manufacturers the Sapien valve is speaking out to dispute recent findings that show TAVI to have less than optimal results.  Of course, the author at the site, Med Latest says it best, “Setting aside the conflict of interest stuff, which might be a red-herring, what we’re left with is a situation where evidence-based medicine, while being something all would sign up to, is not that straightforward.”


[1] Several cardiologists and cardiac surgeons contributed to this article.  However, given the current politics  within cardiology, none of these experts were willing to risk their reputations by publically disputing the majority opinion.  This is certainly understandable in today’s medico-legal climate in wake of widespread scandals and credibility issues. However, all quotes are accurate, even if unattributable with minor formatting (such as the addition of quotations, and paragraph headings have been added for increased clarity of reading in blog format.)  I apologize for the ‘anonymous nature’ of my sources in this instance – however, I can assure you that these ‘experts’ know what they are talking about.

  [All commentary by Cartagena Surgery are in italics and brackets]. 

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As part of our continuing discussions on Valvular disease, we are talking to Dr. Didier Lapeyre, a French cardiothoracic surgeon who currently resides in Switzerland.

if you look close you can see the valve leaflets

Talking with Dr. Didier Lapeyre, MD

I spent the morning talking to Dr. Didier Lapeyre, a cardiothoracic surgeon (via Skype). It was a fascinating discussion, and opportunity to ‘pick the brain’ of one of cardiac surgery’s elite surgeons and researchers. As we’ve mentioned before, Dr. Lapeyre is the ‘Father of the modern valve” and a true innovator in the field. His developments in artificial heart technology, mechanical valves and assistive devices have changed the field of cardiac surgery immeasurably, and have saved countless lives around the globe, so it was a pleasure and an honor to speak with him.  Since he is such an accomplished surgeon, and has such a wealth of knowledge, we had a lot of talk about.  It’s also too much to talk about in just one post, so I will be breaking into a couple of different discussions since it is such a great opportunity to bring to his many years of knowledge and experience to my readers here – which in itself, is a daunting but certainly worthwhile task. (It’s not everyday that I get to speak with one of the pioneers of the field).

I. Introduction to Dr. Didier Lapeyre

II. The Lapeyre devices and contributions to cardiac surgery

III. Current issues in cardiac valve replacement

IV. The future of valve replacement

But first, an introduction: Dr. Didier Lapeyre, MD, Cardiothoracic surgeon

Dr. Didier has spent the majority of his fifty + years in the field researching and developing valve technology and he is arguably, the expert in this field.  He has developed several heart valves and in addition to the current valve he is developing, holds five patents for these devices.  He also has four other patented artificial heart designs.  He is the Director and CEO of Lapeyre Medical LLC, and the former president and director of medical affairs for Triflo Medical Incorporated[1].

Learned from the best

After graduating from medical school at Claude Bernard University, Alexis Carrel Medical School in Lyon, France in 1957, he completed his general surgical residency at Claude Bernard University before becoming the chief resident in the cardiothoracic surgery program under Dr. Pierre Marion, one of the French pioneers in cardiac surgery in 1967.

Dr. Lapeyre then traveled to Rome, Italy and joined the department of surgery at the School of Medicine where he designed and developed a ventricular assist device for use in cardiovascular research.  He then returned to France in 1972 to work with Dr. Alain Carpenter, who is known as the father of mitral valve repair[2].  During the ten years he worked with Dr. Carpentier, Dr. Lapeyre helped to develop the first totally artificial heart.

Dr. Didier Lapeyre then headed the Aerospatial Total Artificial Heart Program, while he served as an assistance professor at the illustrious Texas Heart Institute.  While serving as a designer and medical officer at the Aerospatial program, he submitted four patents for his developments.

In 1987, he went on to work at another heart valve program, the Dassault – Aviation Heart Valve Program, which was affiliated with Texas Heart Institute.  While this seems like an unlikely partnership between heart surgery and aviation, during this period, Dr. Lapeyre submitted four patent applications for mechanical valves.

In 1996, he became president of Triflo Medical before establishing his own company in 2002, which is dedicated to the design, development and innovation of prosthetic heart valves.  He is currently working on a new artificial valve that addresses the current problems in existing technologies by eliminating the need for anti-coagulation.


[1] Dr. Lapeyre was previously involved in a legal action with this corporation in the ninth circuit court of the United States (central California).  Dr. Lapeyre ultimately won a multi-million dollar countersuit in this action.

[2] In 2005, Dr. Carpentier received the prestigious Medallion of Scientific Achievement from the American Association for Thoracic Surgery (AATS).  It was only the fifth time such an honor was bestowed, and the first time it was awarded to someone outside the United States.  (Other notable recipients include the mega-giants of cardiac surgery, Michael E. Debakey and rival, Denton Cooley.)

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Recently readers have contacted Cartagena Surgery to contribute to our many ongoing discussions on issues in cardiology, and cardiac surgery.

One of the points that readers have brought up has been the massive attention that TAVI/ TAVR has gotten from the media (and admittedly, we here at Cartagena Surgery are guilty of this), to the detriment of other issues in medicine and surgery.

In an attempt to address this very valid comment, we have started a series of posts looking at other issues in cardiac surgery – specifically in the area of valvular disease(s) and valvular replacement – and why it is important to re-focus our attention to these conditions such as infective endocarditis, mitral and tricuspid valve disorders, as well as bicuspid aortic valve disease.

Valve Disease and Dr. Didier  Lapeyre

In a current environment where TAVI/ TAVR dominate the landscape of discussion regarding valvular disease, other serious and persuasive problems in valvular disease treatments remain largely unaddressed.  The domination of conversations and considerations regarding the use of ‘less invasive’ mechanisms to correct aortic stenosis in the extreme elderly is something that could only be considered in the wealthiest of nations.

Burden of disease

Elsewhere in the world, and in the minds of more globally aware citizens, more important consideration is given to the burden of valvular disease across all populations including young adults and children.  In fact, in my limited travels, it is this scenario that encountered with much more frequency than the “frail octogenarian” that TAVI is designed for.

(For information on the burden of valvular disease in emerging countries – read The Need For A Global Perspective On Heart Valve Disease Epidemiology. )

Then why, as so many other cardiac surgeons and other authors have asked – are we expending some many resources on this minority population[1] to the exclusion and detriment of other developments in cardiac surgery?

Does TAVI detract attention from more common problems in cardiac surgery?

Some may argue, that TAVI/ TAVR is adjacent to, not exclusive to, the development of other improvements and advancements in the field but in my opinion that is a naïve view of the world.  Money and resources are not endless, and corporations and institutions expending large sums investing in transcatheter therapies are certainly not devoting similar resources to such mundane causes such as improving existing therapies.

Dr. Didier Lapeyre

But sometimes it takes a leader, and a legend to do these things, and that’s where Dr. Didier Lapeyre comes in.  As one of the original innovators of mechanical valve technology, he is not content to rest on his laurels or in the pages of medical textbooks.  As he and his colleagues note, current mechanical valve technologies continue to leave much to be desired.  As Zilla et. al. noted back in 2007, “Prosthetic heart valves: catering for the few?” this technology has been essentially stagnant for the last several years despite an enormous need, worldwide for a safe, durable mechanical valve.

Current therapies for valvular disease consist of two options; each with significant drawbacks.  The bioprosthetic or tissue valve requires no additional therapies after implantation but durability leaves much to be desired, making it inappropriate for most young candidates.

The trials and limitations of true mechanical valves are well-known.  As a foreign, metallic material, these valves are prone to cause platelet breakage, and hypercoagulability.  This leads to the dreaded thromboembolic complications of valve thrombosis and cerebral vascular accident.

If the heightened risk of post-TAVI stroke gives us pause in our frail elderly population, consider the elevated risks inherent with mechanical valves and their target population; children and young adults.

At present, the current solution of lifetime anticoagulation for patients with mechanical valves is a stopgap solution at best.  Problematic, potentially dangerous, and unpredictable are excellent descriptions of anti-coagulation with warfarin.  Unavailable and unrealistic are often as accurate; particularly when describing potential use in third-world populations.

After a recent post, talking about controversies and discussions in cardiac surgery in regards to TAVI, Dr. Lapeyre contacted Cartagena Surgery to add his thoughts on the issue.

This has opened a dialogue – and offers a new and interesting opportunity for my readers to hear about Dr. Lapeyre, his work, and (hopefully), the future of mechanical valves in addition to talking about related valvular conditions and treatments.


[1]  As we have argued several times, at Cartagena Surgery, many of the people who have been deemed ‘frail elderly ‘by their cardiologists can be successfully treated with conventional surgery.

References

Current Anti-coagulation recommendations:

Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH; American College of Chest Physicians.  2012. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e576S-600S.

Akhtar RP, Abid AR, Zafar H, Khan JS. (2009).  Anticoagulation in patients following prosthetic heart valve replacement.  Ann Thorac Cardiovasc Surg. 2009 Feb;15(1):10-7. Study from Pakistan, where rheumatic heart disease remains common.  Also looks at genetic and racial differences in response to anti-coagulation. Readers will also notice that this study demonstrates the wide disparities in global medicine as discussed above.  How many western patients received a ball and cage valve in 2003?

Cannegieter SC, Rosendaal FR, Briët E. (1994).  Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses.   Circulation. 1994 Feb;89(2):635-41.  Review.  [Linked in text above.]  While this article is considerably dated (based on data prior to 1993) it gives an excellent overview of the many problems/ complications in mechanical valve replacement. However, the statistics cited in their work may differ considerably from more recent results. (Presumably, the rate of ‘real world’ complications are much higher than what I see cited here.)

Matsuyama K, Matsumoto M, Sugita T, Nishizawa J, Yoshida K, Tokuda Y, Matsuo T. (2002).  Anticoagulant therapy in Japanese patients with mechanical mitral valves.  Circ J. 2002 Jul;66(7):668-70. A smaller scale Japanese study.

Not available as free text: Links to abstracts, when available

Taniguchi S, Hashizume K, Ariyoshi T, Hisata Y, Tanigawa K, Miura T, Odate T, Matsukuma S, Nakaji S, Eishi K. (2012).  Twelve years of experience with the ATS mechanical heart valve prostheses.  Gen Thorac Cardiovasc Surg. 2012 Jul 6.

Van Nooten GJ, Caes F, François K, Van Bellleghem Y, Bové T, Vandenplas G, Taeymans Y.  (2012).  Twenty years’ single-center experience with mechanical heart valves: a critical review of anticoagulation policy.  J Heart Valve Dis. 2012 Jan;21(1):88-98

Brown JW, Fiore AC, Ruzmetov M, Eltayeb O, Rodefeld MD, Turrentine MW. (2012).  Evolution of mitral valve replacement in children: a 40-year experience.  Ann Thorac Surg. 2012 Feb;93(2):626-33; discussion 633. Epub 2011 Dec 7. This article talks about why we still need to improve and innovate new valve technology – high mortality in this population.

Suri V, Keepanasseril A, Aggarwal N, Chopra S, Bagga R, Sikka P, Vijayvergiya R. (2011).  Mechanical valve prosthesis and anticoagulation regimens in pregnancy: a tertiary centre experience.  Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):320-3. Epub 2011 Oct 1.  Another important issue that affects our decisions to use mechanical or tissue valves.

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