Edward Lifesciences and TAVI wins again..but do patients?

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.



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).


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.


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.


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.

The truth about TAVI/ TAVR

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].


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.


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.


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.


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].


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.


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


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.


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).


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].


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.


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.


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.


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].


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.


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.


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.


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]. 

Readers write in: TAVI

Thanks again to ‘Lapeyre’, who as it turns out is Dr. Didier Lapeyre, a renowned, French cardiothoracic surgeon credited with the development of the first mechanical valves.

Dr. Didier Lapeyre was gracious enough to send some additional literature to add to our ongoing discussions regarding severe aortic stenosis and TAVI/ TAVR therapies.  He also commented that the best way to avoid these ‘high risk situations’ is by earlier intervention with conventional surgery – something we discussed before in the article entitled, “More patients need surgery.”

He also points out that ‘elderly’ patients actually do quite well with aortic valve replacement and offers a recently published meta-analysis of 48 studies on patients aged 80 or older.

As readers know, on June 13, 2012 – the FDA ruled in favor of expanding the eligibility criteria for this therapy.  Previously, this treatment modality, due to its experimental nature and high rate of complications including stroke and serious bleeding, has been limited in the United States to patients deemed ineligible for aortic valve replacement surgery.

Now on the heels of the Partner A trial, in which researchers reported favorable results for patients receiving the Sapien device, the FDA has voted to approve expanding criteria to include patients deemed to be high risk candidates for surgery.  As we have discussed on previous occasions, this opens the door to the potential for widespread abuse, misapplication of this therapy and potential patient harm.

In the accompanying 114 page article, “Transcatheter aortic valve implantation (TAVI): a health technology assessment update,” Belgian researchers (Mattias, Van Brabandt, Van de Sande & Deviese, 2011) looking at transcatheter valve procedures have found exactly that in their examination of the use of TAVI worldwide.

Most notably, is the evidence of widespread abuse in Germany (page 49 of report), which has become well-known for their early adoption of this technology, and now uses TAVI for an estimated 25 – 40% of valve procedures*.  Closer examination of the practices in this country show poor data reporting with incomplete information in the national registry as well as a reported mortality rate of 7.7%, which is more than double that of conventional surgery.  Unsurprisingly, in Germany, TAVI is reimbursed at double the amount compared to conventional surgery**, providing sufficient incentive for hospitals and cardiologists to use TAVI even in low risk patients. (and yes, german cardiologists are often citing “patient refused surgery” as their reason, particularly when using TAVI on younger, healthy, low risk patients.)

In their examination of the data itself, Mattias et al. (2011) found significant researcher bias within the study design and interpretation of results.  More alarmingly, Mattias found that one of the principle researchers in the Partner A study, Dr. Martin Leon had major financial incentives for reporting successful results.  He had recently received a 6.9 million dollar payment from Edward Lifesciences, the creators of the Sapien valve for purchase of his own transcatheter valve company.   He also received 1.5 million dollar bonus if the Partner A trial reached specific milestones.  This fact alone, in my mind, calls into question the integrity of the entire study.

[Please note that this is just a tiny summary of the exhaustive report.]

Thank you, Dr. Lapeyre for offering your expertise for the benefit of our readers!

* Estimates on the implantation of TAVI in Germany vary widely due to a lack of consistent reporting.

** At the time of the report, TAVI was reimbursed at 36,000 euros (45,500 dollars) versus 17,500 euros (22,000 dollars) for aortic valve replacement.

For more posts on TAVI and aortic stenosis, see our TAVI archive.


Mattias, N., Van Brabandt, H., Van de Sande, S. & Deviese, S. (2011).  Transcatheter aortic valve implantation (TAVI): a health technology assessment .  Belgian Health Care Knowledge Centre.

Vasques, F., Messori, A., Lucenteforte, E. & Biancari, F. (2012).  Immediate and late outcome of patients aged 80 years and older undergoing isolated aortic valve replacement: a systematic review and meta-analysis of 48 studies.  Am Heart J 2012; 163: 477-85.

well, we knew this would happen…Edward Lifesciences 2: patients: 0

As reported by heartwire, and a savvy reader, Lapeyre here at Cartagena Surgery, the FDA has gone ahead and approved TAVI/ TAVR for patients that are eligible for open surgery.  [We must think alike, as I was drafting this post when I received the reader mail].

Despite the FDA’s previously cited concerns over the excessive stroke rate with the Sapien device (as discussed in the article re-posted below) – the FDA approved the use of this therapy as an alternative to surgery on June 13th.

Now we can sit back and watch as the up selling of this device to the public as news hits the US media and the television advertisements begin.  Soon this device will crowd out surgery as interventionalists cite “patient refused surgery” as the criteria for implantation, no matter what the best interest of the patient really is.  I wonder if they will even disclose the heightened stroke rate when they start implanting this into patients at a much higher rate.  Of the 12 members of the FDA panel, only one member voted against the expansion criteria.

As reported by Shelley Wood in a follow-up Heartwire article , only Dr Valluvan Jeevanandam spoke out against expanding the criteria for use, stating,   “I think this is a very good technology, and it gives us an alternative to AVR surgery, and I’m sure the device will continue to get better,” Jeevanandam, a cardiovascular surgeon, told heartwire after the meeting.

“However, at the current time, compared with standard AVR, this device has a higher stroke rate and a high rate of aortic insufficiency, did not meet the criteria for noninferiority* in males, and has a high incidence of vascular complications.”

These are all issues that need to be very clearly explained to patients as part of the informed-consent process, he stressed. Otherwise, patients who are “enamored at the idea of avoiding a sternotomy” may not fully understand these risks.”  

I fully concur with Dr. Valluvan Jeevanandam except that I might re-phase the term ‘enamored of.’  Actually, I think our so-called peers need to quit coercing patients by intentionally scaring them – in order to bill more procedures out of them.  [Don’t believe it?  Then check out Mark Midei and our overstenting archives.]

I will continue to champion well-established therapies with strong long term data.  I know this will get me labeled as ‘old-fashioned’ (or worse) but as we’ve seen in cardiology – numerous times; easy is not always the best answer..

The is no easy button

Yes, conventional surgery hurts – it’s not glamorous, it’s not pretty.  But it’s (statistically) darn safe these days, and most of the surgeons doing it have done it thousands of times.. Even the bioprosthetic valves have a long durability than previously thought – meaning not everyone has to take warfarin..

We shouldn’t exploit people’s fears of surgery to use quasi-experimental procedures, no matter how “cool” they sound..

* I hope readers remember that ‘noninferiority’ is a lesser standard that superior to, or even EQUAL to..

FDA flags strokes, trial conduct, as TAVI maker seeks expanded role for Sapien – from Heartwire.com (Shelley Wood).

Gaithersburg, MD – A higher risk of stroke and differences in how patients randomized to different procedures were actually treated and evaluated within the PARTNER A trial, which compared transcatheter aortic-valve implantation (TAVI) with surgery, are issues the US Food and Drug Administration (FDA) hopes its expert advisors can help clarify in weighing the pros and cons of expanding approval of the Sapien transcatheter valve (Edwards Lifesciences) [1,2]. Those issues and others are detailed in an FDA briefing document, posted online today, that the agency’s Circulatory System Devices Panel will consider in advance of Wednesday’s meeting.

As previously reported by heartwire, the FDA last year reviewed and subsequently approved the Sapien valve and transfemoral delivery system in patients not suited to open-valve replacement, based primarily on the PARTNER B results. Wednesday’s meeting, drawing heavily on the  PARTNER A results, will help the FDA decide whether to expand approval to high-risk patients who are surgery eligible and whether to approve the transapical approach also tested in PARTNER A.

In briefing documents posted online today, the FDA directed its advisors to pay special attention to a number of issues relating to trial conduct as well as patient outcomes.

In particular, the FDA review cites the “doubling” of neurological events seen in the Sapien-treated patients in the first 30 days postprocedure, with a higher stroke rate seen among transapical as compared with the transfemoral group.

The FDA documents also query “attempt-to-treat” decisions, including the higher number of patients randomized to surgery in whom no treatment was attempted; longer delays to treatment in surgical patients; and the higher number of concomitant operations seen in the surgical aortic-valve-replacement group—all factors that could have influenced adverse-event and survival rates in this group.

FDA is also asking its expert panel to weigh in on whether both the transfemoral and transapical approaches should be approved, given the numerically higher mortality in the transapically treated patients as compared with the transfemorally treated patients in the device arm.

General questions the FDA panel will be answering Wednesday include those related to the issues above, as well as to different outcomes seen in men and women, the importance of paravalvular regurgitation seen in patients treated with TAVI, valve durability, the required anticoagulation/antiplatelet regimen, and obtaining true informed consent.

Voting questions center on whether the evidence is sufficient to demonstrate safety and efficacy and whether the benefits of the new device outweigh the risks.

Industry analysts reading the tea leaves in the FDA’s review see the agency’s briefing document as largely promising, with Wells Fargo’s Larry Biegelsen predicting a “tough day, but positive panel outcome” and JP Morgan’s Michael Weinstein stating that the FDA synopsis contained “no major surprises; positive outcome expected.”

In other cardiology news, 

New guidelines recommend the discontinuation of prasugrel a full seven days before surgery to prevent catastrophic bleeding complications. (The cynical side of me expects to see a bigger push by the industry to use prasugrel now that clopidogrel is generic.)  Expect to see a couple more “Ask your doctor” ads..

Update: Medicare to cover TAVI/ TAVR

In an update to a previous story here at Cartagena Surgery, in the attached article, “Medicare to pay for TAVI” from Medpage.com by Chris Kaiser, the guidelines for CMS payment for TAVI/ TAVR have been released.   These criterion include the restriction that only surgery ineligible patients be included and that implanting surgeons must participate in the TAVI registry.

More importantly, this criteria requires that TWO cardiac surgeons determine the patient’s suitability to withstand surgery versus TAVI.  This is a crucial requirement as we’ve discussed before, since only a surgeon can accurately decide/ predict how a patient might tolerate surgery.  (Multiple previous studies showed that primary care providers and cardiologists were poor judges of patient’s surgical risk. )  Also, the lack of this requirement in Europe has caused several ethical problems as interventional cardiologists began the widespread implantation of experimental technologies in lower risk patients (particularly in Germany.)

Six month TAVI/TAVR data released

The Core Valve by Medtronic

Medtronic, the makers and financial backers of a recent study on the Core Valve used for percutaneous aortic valve replacement (aka non-surgical valve replacement) released their findings showing the six month mortality data on patients receiving this valve.

This study which was performed using data from European cardiologists (who have been using this technology longer) were unsurprising – with a higher risk of stroke and overall mortality.  Notably, this study was performed on patients deemed to be ‘at high risk’ for surgery, not ineligible for surgery.  As we’ve discussed before, the term ‘high risk’ is open to considerable interpretation.

A total of 996 frail, elderly patients at high risk for heart surgery were  implanted with Medtronic’s CoreValve device, used to treat severe narrowing of  the aortic valve. Mortality rates at one month and six months were 4.5% and  12.8%, respectively. Stroke rates were 2.9% and 3.4%.

Medtronic said the rates  were consistent with previously reported data from national registries in Europe.”

Unfortunately, the general media’s coverage of these findings have been less than straightforward as Bloomberg proclaims in blazing headlines, “Edwards heart valve skirts rib-cracking for a 2.5 billion dollar market.”  That’s a pretty eye-opening headline that manages to avoid mentioning the real issues – longevity and durability.

Another article from business week proclaims, “Heart Valves found safe.”  Safe, I guess is a relative term – if you aren’t one of the 12.8% that died within six months..

Illustration showing the core valve in place

More about Aortic Stenosis and Valve Replacement therapies at Cartagena Surgery:  (you can also find a link to these stories under the TAVI tab on the sidebar.)

Aortic Stenosis as Heinz 57

More patients need surgery

Aortic Stenosis, surgery and the elderly

Aortic stenosis and TAVI

Aortic Stenosis: New Recommendations for TAVI

Transcatheter Valve Therapies: an overview

TAVI and long-term outcomes

Peri-operative outcomes with TAVI

Talking about TAVI/ TAVR with Dr. Kevin Brady

Will Medicare cover TAVI?

Will Medicare cover TAVI/ TAVR?

Updates to this story have been posted here.

In an article re-post from the Heart.org, Lisa Nainggolan discusses a recent memo issued by Medicare & Medicaid services (CMS) on potential coverage for TAVI/ TAVR.    This memo lays out the necessary criteria and conditions that must be met for CMS coverage.

Don’t have medicaid or medicare?  Well, the privately insured should still sit up and take notice:  CMS decisions usually set the pace for everyone else – meaning, if Medicare won’t pay for it – then Blue Cross, Anthem and most of the big private insurances won’t either.

CMS draft of proposed coverage – the Heart.org 

Lisa Nainggolan

Baltimore, MD – The US Centers for Medicare & Medicaid Services (CMS) has issued a memo detailing its proposed coverage for transcatheter aortic-valve replacement (TAVR) [1]. The move follows a request for national coverage determination (NCD) from the ACC and Society for Thoracic Surgeons (STS), made last September.

The memo—which is a draft and will be open for public comment until March 3—outlines the conditions under which the CMS will cover TAVR, also known as transcatheter aortic-valve implantation (TAVI), and follows hard on the heels of an expert consensus document on the new technology, published earlier this week.

An estimated 45 000 patients have received TAVI worldwide, with most procedures so far being performed in Europe. US approval of the Edwards Sapien valve at the end of last year means that the country must now gear up to introduce this technology nationwide, and the expert guidance has been designed to act as a roadmap for the rollout of TAVI in the US.

Five conditions must be met for Medicare coverage of TAVR

TAVR will be covered for the treatment of severe symptomatic aortic-valve stenosis only, says the CMS, and the following five conditions must be met:

  • The procedure is performed for an approved indication with a valve and implantation system that has received FDA approval for this indication.
  • Two cardiac surgeons have evaluated the patient’s suitability for open valve-replacement surgery. (traditional cardiac surgery)
  • The procedure is performed in a facility that meets certain requirements with regard to surgical and interventional cardiology expertise. In addition, institutions with prior TAVR experience must participate in ongoing trials or postapproval studies, and all centers performing TAVR must commit to the “heart-team” concept and enroll in a prospective national TAVR study.
  • TAVR must be carried out by sufficiently qualified and experienced physicians.
  • The treating team must participate in a national registry that enrolls TAVR patients and tracks the following outcomes: major stroke; all-cause mortality; minor stroke/transient ischemic attack; major vascular events; and acute renal injury.

For unlabeled uses of TAVI, the CMS proposes coverage only in the context of a clinical trial, for which it lists 13 conditions.

The CMS also indicates that it will not cover TAVR for any other indications not specified in its memo, nor will it cover the procedure in patients who also have concomitant conditions, including: mixed aortic-valve disease; isolated aortic regurgitation; untreated clinically significant coronary artery disease requiring revascularization; hypertrophic cardiomyopathy; echocardiographic evidence of intracardiac mass; significant aortic disease; and severe obstructive calcification or tortuosity of the iliofemoral vessel or small vessel size.

It’s a mixed win for American cardiologists and cardiac surgeons – and certainly opens the door to the expanded use of this criteria.  The good news is that CMS is taking the initiative to stem off a flood of inappropriate procedures.  The release of this memo, along with the recent publication of new guidelines re-affirming the role of CABG, and relegating PCI to specific circumstances  is almost certainly a response to the numerous scandals and allegations affecting cardiology in 2011 (and ongoing.)

Which hospitals should have TAVR/ TAVI programs?

This article outlines the basic requirements for a safe and successful TAVR program – including the minimum skill requirements for surgeons and interventionalists.

But I suspect – it won’t be long before more and more hospitals open their own programs.  This article highlights the financial gains for hospitals with TAVR programs.

TAVI/ TAVR and AVR in Arizona with Dr. Brady

Sat down today with Dr. Kevin Brady to talk about TAVI, or as he corrects me with a smile, TAVR (R is for Replacement).  Dr. Brady is a cardiothoracic surgeon, and one of the few currently performing TAVI/ TAVR here in Arizona.  As we’ve discussed before, I have mixed feelings on this procedure but have elected to provide the information here for my interested readers.

Dr. Brady shares many of my apprehensions, that the public will come to view this currently quasi-experimental treatment for very high risk, and inoperable patients with Aortic Stenosis as a ‘easy fix’.   We discuss this at length, and he reviews the current recommendations guiding the implementation of TAVR programs, and the TAVR registry with me.

As part of this discussion, I have invited Dr. Brady to write a short post here, explaining the procedure, patient selection criteria and other facts about TAVI/ TAVR.  With over 41 Core-valve implantations (since March 2011, as part of the Core Valve Pivotal trial) and seven Sapien valve implantations this month, he certainly qualifies as an expert on the topic.

Dr. Brady will be able to give readers a more in-depth perspective on this procedure.  As all of you know, I have taken a fairly cautious stance on this issue.  (I haven’t talked him into letting me observe yet, but I am working on it.)

Dr. Kevin M. Brady, MD

Southwest Heart & Lung


10930 North Tatum Boulevard, Suite 103

Phoenix, Arizona 85020

Tele: 602-263-7600

Aortic Valve Replacement & the elderly

I just read an interesting article in the Annals of Thoracic Surgery.

Unfortunately, the full-text article is not available for free – but I did find a nice article abstract (which I’ve posted below.)  It confirms some of the previous discussions we’ve had here at Cartagena Surgery on the role of surgery in Aortic Stenosis, even in ‘elderly’ patients.  [I put elderly in quotes since the definition can be fairly elastic depending on who is doing the judging.]

The article below is from Medscape.com

Aortic valve replacement in the elderly: the real life.

Ann Thorac Surg. 2012; 93(1):70-8 (ISSN: 1552-6259)

Langanay T; Flécher E; Fouquet O; Ruggieri VG; Tour Bde L; Félix C; Lelong B; Verhoye JP; Corbineau H; Leguerrier A Department of Cardiovascular and Thoracic Surgery, University Hospital, Rennes, France.

BACKGROUND: Aortic stenosis is of concern in the elderly. Although aortic valve replacement provides good long-term survival with functional improvement, many elderly patients are still not referred for surgery because of their age. Percutaneous aortic valve implantation offers an alternative to open-heart surgery. Concerns about the management of aortic valve stenosis in the elderly will be reviewed.

METHODS: We retrospectively analyzed 1,193 consecutive aortic valve replacements, performed in octogenarians since January 2000. A total of 657 patients (55%) had at least one associated comorbidity (eg, respiratory failure) and 381 (32%) associated coronary lesions. Valve replacement was the only procedure in 883 patients (74%), and was associated with coronary revascularization in 262 cases, or with another cardiac procedure in 48 patients.

RESULTS: Overall operative mortality was 6.9% (83 of 1,193 patients); 5.5% for single replacement and 11.5% if associated with coronary artery bypass surgery. Univariate and multivariate analyses identified 11 operative risk factors related to general status, cardiologic condition, and the procedure itself: older age (p< 0.015); respiratory failure (p <0.03); aortic regurgitation (p <0.001); emergency surgery (p <0.0029); New York Heart Association class IV (p < 0.0007); right heart failure (p < 0.03); atrial fibrillation (p < 0.04); impaired ejection fraction (p < 0.001); coronary disease (p < 0.01); redo surgery (p < 0.02); associated coronary revascularization (p < 0.008).

CONCLUSIONS: Today, valve replacement has acceptable low hospital mortality, even in the elderly. Thus, older patients should not be denied surgery due to their advanced age alone. Conventional surgery remains the gold standard treatment for aortic stenosis; the decision should be made on an individual basis. If several risk factors suggest very high-risk surgery, then percutaneous valve implantation should be considered instead.

In more disturbing news:

As predicted, the unproven ‘easy option’ of TAVI is now being pursued by more low-risk patients.  These lower risk patients are people who should have been encouraged to undertake the more durable, safe and proven surgical therapy [Aortic Valve Replacement.]  I guess this just shows how quickly those new recommendations [for patient protection and safety] were thrown out the window.

In this article (posted below) by Kurt Ullman at Medpage Today – German researchers discuss their preliminary findings and discuss the use in low risk patients.

The bar for transcatheter aortic valve implantation (TAVI) is dropping as more lower-risk patients are undergoing the procedure and their outcomes are favorable, a single-center study from Germany found. [Unfortunately – as we’ve seen so many times in the past, and as I am finding out while preparing this presentation on the Syntax trial – studies such as this can be quite deceiving – and LONG term data is needed. – Cartagena Surgery].

When stratified by quartiles based on enrollment date, Q1 patients had higher logistic EuroSCOREs, higher Society of Thoracic Surgeons (STS) scores, and higher median N-terminal pro-B-type natriuretic peptide levels compared with those enrolled later in Q4, noted Nicolo Piazza, MD, PhD, and colleagues from the German Heart Center in Munich.

Although there were significant decreases in 30-day and six-month mortality from Q1 to Q4 in the crude analysis, after adjustments for baseline characteristics, the significant differences disappeared (HR 0.29 for 30-day mortality and HR 0.67 for six-month mortality), according to the study published online in the Journal of the American College of Cardiology.

“These results suggest that underlying comorbidities play an important role in acute and intermediate-term survival after TAVI,” the researchers wrote.

The researchers noted anecdotal information suggesting a shift toward using TAVI in patients who are less sick than those enrolled in premarket trials. Additionally, the next wave of trials involving the CoreValve (Medtronic) and the Sapien XT (Edwards Lifesciences) devices will involve intermediate to high surgical risk patients, providing “yet another indication that TAVI is being directed at the treatment of lower and lower surgical risk patients,” Piazza and colleagues wrote.  [There are significant ethical considerations here which seem to be ignored – similar to criticisms of the Syntax trial – Cartagena Surgery.]

A single-center French study of low-risk TAVI patients found the procedure to be safe in this population. The study was presented at the European Society of Cardiology meeting in Paris.

The impact on this shift in patient selection was uncertain, they said, prompting a retrospective review of 420 patients who underwent TAVI at their institution from June 2007 to June 2010.

The consensus that a patient was suitable for TAVI was derived from a team that comprised cardiologists, cardiac surgeons, and anesthesiologists. This team approach is exemplified by the recent announcement that the American College of Cardiology and the Society of Thoracic Surgeons will jointly sponsor a TAVI registry to monitor the safety and efficacy of the procedure as it rolls out in the U.S.

Patients received either the CoreValve or Sapien device, the latter of which was just approved for use in the U.S. based on the PARTNER trial. PARTNER found that TAVI was as good as surgery in high-risk patients with severe aortic stenosis. [‘as good as’ – ah.. another ‘non-inferiority’ study….. view with skepticism folks..]

Researchers divided patients into four quartiles of 105 patients each. Those in Q1 were seen earlier in the study time frame than those in Q4.

Compared with Q4, Q1 patients had higher EuroSCOREs (25.4% versus 17.8%, P<0.001), STS scores (7.1% versus 4.8%, P<0.001), and NT-proBNP levels (3,495 versus 1,730 ng/dL, P<0.046).

There were significantly less transfemoral access approaches from Q1 to Q4, with a concomitant rise in transapical approaches. There also were significantly less intubations moving from Q1 to Q4, and the use of contrast significantly decreased over time.

Researchers noted that transfemoral complications decreased by 17% from Q1 to Q4 (P=0.008), but found no significant differences in the rate of stroke or transient ischemic attack or the need for a permanent pacemaker.

However, there was a shift in the later quartiles toward the treatment of younger patients with fewer comorbidities and lower surgical risk scores, Piazza and colleagues wrote.

Univariable analysis for 30-day mortality showed it was associated with age, STS score, atrial fibrillation, previous heart surgery, and previous stroke (P<0.10).

The factors associated with six-month mortality were age, logistic EuroSCORE, STS score, left ventricular ejection fraction, atrial fibrillation, previous cardiac surgery, chronic obstructive pulmonary disease, and N-terminal pro-B type natriuretic peptide (P<0.10).

Because only baseline characteristics were included, the authors noted the possibility that procedure-, operator-, or device-related factors might influence both 30-day and six-month mortality. The study is also limited by potential unmeasured confounding.

The investigators cautioned that little is known of the long-term durability of these devices should they be routinely implanted in younger patients with a longer expected life span.  [especially since the lifespan of the patients these valves were designed for was six months to one year..]

Piazza is a consultant and proctor for Medtronic and CardiAQ. Other authors revealed consultant status with Medtronic and Edwards Lifesciences, or instuctors for Medtronic

The TAVI Registry, journey to the UK and other news

London Bridge, at night.

Just returned from a quick trip to London, UK to interview a couple of fantastic thoracic surgeons. (You can read the interview here.)

In the meantime, a midst multiple conflicting reports regarding the use and safety of TAVI (percutaneous aortic valve replacement) the ACC and STS have finally come together to create a TAVI registry, similar to the PCI and cardiac surgery registries.  The new registry will be used to track TAVI procedures and outcomes.  Hopefully, by gathering information in a standardized fashion and collecting data on patient outcomes, we can finally answer the essential question surrounding TAVI: Is It Safe?

As someone who is intimately involved in the STS database – I can assure readers that if STS is involved, data collection will be extensive, cumbersome and overly complicated.  (The adult cardiac surgery data collection form is fourteen pages long.)  However, the database will allow doctors to identify whether complications are device related/ procedure related or operator related.  (For example, are post-procedural strokes caused by the valve (device related) itself, or by the person (operator related) inserting it?  It will also track 30 day mortality – and the causes of mortality.  (ie. Was the death coincidental versus bleeding/ stroke/ kidney failure, etc?)  The registry will also track one year outcomes – but unfortunately – the essential question  – Is it Safe long-term?  will remain unanswered.

In Big Pharma news – I had the good fortune to meet (and talk to at length) one of the inside investigators* for GlaxoSmithKline.  He was a delightful and charming interview – and it was a fascinating inside look at the future of pharmacology, pharmacy, drug development and marketing.

As readers know – I have vilified and railed against pharmaceutical companies in the past (and most likely – will continue to do so) but it was an excellent opportunity to see the other side of a blighted industry.  [Here at Cartagena Surgery – I may have unabashedly strong opinions, but I do try to be fair.]

As an investigator for a pharmaceutical company, his position is somewhat akin to George Clooney’s character in the recent film ‘Up in the Air’.  He investigates company employees as well as independent contractors who represent the company for moral, ethical and criminal violations.   In the wake of several serious recent ethical and criminal investigations into the pharmaceutical industry in recent years – companies such as GSK take this duty extremely seriously.  As part of this effort – they hired people like the man I am interviewing today.  Mr. X is surprisingly charming, amiable, and witty.  Somehow as a ‘trigger man’ for a big company, and former NYC police officer, the gentleness, and the compassion emanating from him is unexpected.   He tells me that he has received thank you letters from people who were ‘separated from the company’ on his say-so – and I am not surprised.

We talk about public and health care providers perceptions of the pharmaceutical industry, and trends of the past.  We discuss the previous ‘bribe and gift’ atmosphere of the past – and he gently calls me out for my Pfizer bag from a long-ago conference.  [Ironically, I’ve railed against this bag in the past – it’s from a conference I attended as a student, but hypocrite that I am – have neglected to throw it out.  In my own weak defense – I will say that I never again have accepted or received ‘sponsored’ gifts or items.]  But he’s right – and I accept my scolding, hopefully with the grace it was given.

He talks about one of the new projects that GSK is implementing – and I immediately sit up and take notice.  Phasing out the ‘hootie girls’ as we call the often scantily clad, inappropriately dressed, invariable young, attractive (and always! well-endowed) pharmaceutical representatives that cold call doctors offices with girlish laughs, lots of legs and sample supplies of costly drugs.   No, I will not be sad to see the end of the ‘hootie girls’.

Replacing the hootie girls will be nurse educators.  Instead of pushing costly brand name drugs – they will be restricted from mentioning brand specific medications.. But educate they will.  Hopefully these educators will serve as a resource for healthcare providers – to assist us and inform us without trying influence us.  In many ways – it sounds like GSK may be moving in the direction that we need to go.. Afterall – with millions of millions of people needing treatment (and the vast amount of disease out there)  just obtaining and supplying these patients with the medications they need is a phenomenal effort – and companies can still make a HUGE profit on volume alone.    (And I am not against making a profit – it supports drug research etc..)

But the idea of being able to use the vast amount of information collected from these companies and their volumes of research without rancor, or hardcore skepticism – is encouraging.  If we can build bridges and trust – we can ultimately better serve our patients.. Of course, nothing this big ever goes off without a hitch, and Rome wasn’t build in a day – but it’s a start.. 

It’s a hopeful view from an unlikely source at the end of a very long day that started in one country and ends in another..

* I didn’t get a chance to ask his permission to  write about our meeting – so in fairness, I have omitted his name.

More TAVI news: the STACCATO trial halted, and data from PARTNER A.

The STACCATO trial of TAVI (percutaneous aortic valve implantation) was halted due to problems, and the new data from the PARTNER A trial is less optimistic than previously hoped.  More information from two articles published at the Heart.org (Heartwire.com) are re-posted below:

STACCATO: Transapical TAVI in surgery-eligible patients stopped due to adverse events
    Nov 10, 2011     Michael O’Riordan
San Francisco, CA– A study comparing the transapical approach for transcatheter aortic-valve implantation (TAVI) against conventional aortic-valve replacement surgery was stopped early due to an increase in adverse events, including an increased risk of major stroke and severe paravalvular leakage, in elderly patients eligible for surgery.

Dr Leif Thuesen (Aarhus University Hospital, Denmark), who presented the results of the STACCATO trial today at TCT 2011, said he is concerned about extending the indication of transapical TAVI to include patients who are candidates for surgery, especially given the increased risk of major stroke observed in this trial.

“There is no doubt there are patients who can’t be operated on, and they should be treated with TAVI,” Thuesen told heartwire. “But the patient who can be operated on—here, we should be very, very cautious. It’s the operable patients, the low-risk patients; they should not have the TAVI procedures, but that’s what is happening. We had one patient, for instance, who did not want the conventional operation, so he had the TAVI procedure in Canada. That’s how it is. Indications are slipping.”

The results of the study were presented during the late-breaking clinical-trials session, as well as during a morning press conference. After Thuesen’s presentation to the media, Dr Michael Mack (University of Texas, Dallas) pulled no punches in his criticism of the trial, saying the study was poorly designed and poorly executed. Mack said the trial was designed too optimistically and powered for event rates in the TAVI arm that were too low. Moreover, some of the events that stopped the trial, including one patient in the transapical-TAVI arm who died while on the waiting list for the procedure, skewed the results.

“I think there is some misinformation here, based on invalid trial design, that is likely to hurt the field,” Mack told heartwire.

The STACCATO trial

The STACCATO trial was designed three years ago and included elderly patients with valvular aortic stenosis who could be treated with surgery or transapical TAVI. Based on data from a surgery registry, they anticipated a surgical-event rate—defined as a composite of 30-day all-cause mortality, major stroke, and/or renal failure—of 13.5% and an estimated event rate in the TAVI arm of 2.5%. The study was stopped due to an increase in adverse events in the TAVI arm after the inclusion of 70 patients.

Indications are slipping.

Regarding the primary end point in the transapical-TAVI arm, there was one non-treatment-related death, one left coronary artery blockage, two major strokes, and one patient who had renal failure requiring dialysis. In the surgical arm, there was one case of perioperative major stroke. Other adverse events in the TAVI arm included a transient ischemic attack followed later with a major stroke, two perioperative cases of severe paravalvular leakage, one perioperative aortic rupture, one left main occlusion during balloon valvuloplasty, and one case of major bleeding.

Thuesen emphasized that the study was initiated three years ago and that the transapical TAVI devices at that time were relatively “unsophisticated” and not available in the full range of sizes now on the market. Moreover, he noted that the study investigators were optimistic about the success of TAVI in this population, especially given their absence of clinical events before the study was started, and for that reason they assumed an event rate of 2.5%, which he admitted was “completely wrong.” He noted that the trial began after investigators had performed approximately 40 transapical TAVI procedures.

To heartwire, however, Mack said the event rates were too low and that investigators should have estimated an event rate closer to 13%, similar to the event rate assumed in the surgical arm. Dr Joseph Bavaria (University of Pennsylvania, Philadelphia), on the other hand, saw a silver lining in the data, especially for surgeons. He said that the study shows the great surgical results obtained in patients with an average Society of Thoracic Surgeons (STS) risk score of 3.4.

Discussing the results and the stopping of the trial, Thuesen said that operators are now much better at handling paravalvular leakage, and newer devices might provide a much better fit into the aorta. Moreover, multislice computed tomography (MSCT) is able to provide better preoperative assessments over echocardiography, which was used in STACCATO. Still, despite the limitations of the trial, Thuesen said that in the current phase of development, transapical TAVI is likely inferior to surgery.

Asked about patients who want TAVI despite eligibility for surgery, Thuesen told heartwire that “we should try to persuade them to have surgery, no doubt.” Mack, on the other hand, said that on the front lines surgeons are forced to tell patients that their surgical risks are too low for TAVI and that surgery is the recommended treatment. “The patients don’t want what I’m selling,” said Mack.

[I completely disagree – of course patients want what Dr. Mack is selling – a quick, easy fix.. Who is he kidding??  That’s why it’s important that we make sure the procedure is safe before expanding the indications for TAVI. – Cartagena Surgery].

In a second article published in the last 24 hours over at Heartwire, results from the PARTNER A trial are also less optimistic than expected.
PARTNER QoL data hint transapical TAVI falls short of aortic-valve surgery
Nov 10, 2011     Shelley Wood
San Francisco – Quality-of-life (QoL) data from the PARTNER A trial should prompt a “rethink” of how many transcatheter aortic-valve implantations (TAVI) are performed via the transapical route, investigators say.

New QoL data released today at TCT 2011 show that while high-risk, surgery-eligible patients treated via a transfemoral route in PARTNER A reported substantial QoL benefits compared with surgery in the early weeks postprocedure, this was not the case for patients treated via a transapical route.

In fact, said Dr David Cohen (Saint Luke’s Mid America Heart Institute, Kansas City, MO), who presented the results, “for patients eligible only for the transapical approach, there was no benefit of transcatheter aortic-valve replacement over surgical aortic-valve replacement at any time point, and in fact, QoL tended to be better with surgical replacement both at one and six months.”

Life after TAVI

As previously reported by heartwire, PARTNER A tested the Edwards Sapien valve against surgery in high-risk patients, with all suitable patients randomized to TAVI undergoing a transfemoral procedure if appropriate and a transapical procedure if the patient was deemed unsuitable for a transfemoral approach. At one year, the transcatheter procedures were found to be noninferior to surgical replacement for the primary end point of one-year mortality.

For a number of secondary end points, TAVI and surgery were associated with differences in procedure-related complications and valve performance at 12 months, but the impact of these differences on patient QoL was previously unknown, Cohen said.

For the current analysis, Cohen et al measured QoL in PARTNER A using the Kansas City Cardiomyopathy Questionnaire (KCCQ), the SF-12, and the EQ-5D, with questionnaires administered at one, six, and 12 months.

For the overall comparison, researchers saw differences between TAVI and surgery at three months, but these had disappeared by six and 12 months. What was clear, however, was that there was significant interaction between the treatment effect and the type of TAVI procedure.

Cohen and colleagues therefore conducted further analyses of QoL according to whether patients had undergone a transfemoral or transapical procedure.

QoL improvements

“For the transfemoral group, the message is one that clinicians won’t find surprising,” Cohen said—these largely reflect the QoL findings from PARTNER B. The less invasive nature of the transfemoral [TAVI] procedure results in pretty important differences in QoL at one month, although by six and 12 months the patients have really come together.”

At one month, however, the improvement in QoL was meaningful—in line with about a one to 1.5 level improvement in NYHA class, Cohen said.

“But on the flip side, the transapical group was really somewhat of a surprise and showed certainly no benefit in terms of QoL of transapical over surgery at any time point, not a hint of a benefit. And for several different measures, [transapical TAVI] was actually doing worse. The trends were all toward worse QoL at one month with the transapical approach.”

At one month, scores were numerically lower for transapical TAVI compared with surgery across the various QoL scales used. At six months, this difference was actually “of borderline statistical significance” at p=0.04 for the primary end point (KCCQ overall summary). By 12 months, all differences disappeared.

The hardest cuts

His hypothesis, although it’s yet to be proven in this setting, is that healing from the medial sternotomy is actually easier and less painful than healing from the smaller, cosmetically “better” lateral thoracotomy used for transapical TAVI.

“A lot of what really hurts and impairs breathing and other sorts of things in these patients after cardiac surgery is motion of the wound. So if the wound is fixed, if the sternum is wired back together so it really can’t move, patients heal quite well, and it doesn’t cause a tremendous amount of pain once the first couple days are past. Whereas the smaller incision, the lateral thoracotomy, is always moving every time you take a breath. There is no way to wire that back together. I think it’s a more painful incision for patients to recover from.”

Cohen expects his presentation to meet with much debate, since it’s the first real suggestion that TAVI is not better than surgery, at least via the transapical route.

Indeed, in a morning press conference, surgeons Dr Michael Mack (Baylor Health Care System, TX) and Dr Joseph Bavaria (University of Pennsylvania, Philadelphia) both made the point that many of the US PARTNER centers actually performed very few procedures over the course of the trial, such that the transapical results truly represent a very early experience with this procedure. To heartwire, Bavaria noted that some of these transapical patients actually had complications that kept them in the hospital longer than expected. “I’d like to see the data from the continued-access registry, to see if those patients did better,” Bavaria said.

And Cohen agreed that centers in Europe, which have a longer history with these devices and procedures, may have found ways of improving patient recovery, involving better technique or using local anesthesia or nerve blocks, after transapical TAVI.

Already, however, while some registry data in Europe have pointed to much better results with a TA approach than those reported today, other European data have hinted that alternatives to the transfemoral route, such as the subclavian approach, may yield outcomes closer to those of the transfemoral route. So far, the Medtronic CoreValve is the only established TAVI device (approved in Europe) that can be implanted via a subclavian route. The CoreValve is still in the early stage of its pivotal clinical trial in the US.

Cohen acknowledged that done well, the transapical procedure is “slick, smooth, and quick,” but “we can’t assume just because the incision is small that the procedure is going to be easier to recover from.”

Asked what he thought the future of the transapical approach might be, Cohen replied: “I think it’s going to have a role, but I’m hopeful that this analysis leads us to reconsider the extent of that role. And for places that have access to multiple technologies for doing nontransfemoral procedures, this should be taken into account. And we may want to really rethink how much transapical we do.”

Mack, however, was less concerned, pointing out that the surgery group in PARTNER A did better than expected. “I think we cannot ignore [these results] and say there are not some concerns here . . . but I’m not as concerned about it as the data may [suggest].”

Still, the results should raise some eyebrows, experts speaking to the media seemed to agree. Dr Samir Kapadia (Cleveland Clinic, OH), speaking at the press conference, said, “This is a little bit shocking. This is a learning [moment]—it’s clear we have to improve the transapical procedure.”

Cohen disclosed receiving grant support/research contracts from Abbott Vascular, Boston Scientific, Medtronic, AstraZeneca, and Edwards Lifesciences and consulting/honoraria/speaker’s bureau fees from Daiichi-Sankyo/Eli Lilly, and Medtronic.

Both of these studies were presented at the 2011 TCT (Transcatheter Cardiovascular Therapeutics) conference in San Francisco – going on November 7th through 11th.

What does this mean for Transcatheter therapies such as TAVI?  It means we still have a LONG way to go before we can even begin to consider TAVI as a safe alternative to aortic surgery.  The key phrases of concern are ‘indications are slipping’ which means that everything that we’ve suspected/ feared is already occuring – patients are getting TAVI when they should have surgery – (presumably because it’s considered faster/ easier) and less resky – when as readers know: nothing could be further from the truth.
Here at Cartagena Surgery – we embrace technology, but only when it’s used appropriately.
Note:  Both of these studies have been re-posted verbatim – with no alterations in written content for the benefit of non-subscribers of cardiology publications. [Comments with article text are clearly delineated as my own, in brackets and italics: Cartagena Surgery].

It looks like TAVI is here.

The FDA recently approved the first TAVI device for aortic stenosis.   Currently the device is only eligible for patients who are unable to withstand surgery.   But who will end up making that determination?  The cardiologist who will be implanting the device?  At present – the company manufacturing the Sapien aortic device is recommending that patients be evaluated by a heart surgeon – but if this follows the typical course, I am sure that this recommendation will be abandoned as a matter of course.

Hopefully, the industry (interventional cardiology) will proceed cautiously, after being ‘omce bitten, twice shy” in light of the epidemic overstenting catastrophies.

For more on Aortic stenosis, TAVI and the overstenting controversies – look under the cardiology and cardiac surgery tab.


Here’s the latest news on TAVI in the United States – and the status of the procedure, which is currently undergoing further evaluation by the FDA.

Here are some highlights from the article:

“In July, the FDA’s  Circulatory System Device Panel favored TAVI approval in the U.S. The  panel voted on three items, including: safety, effectiveness and whether  the benefits outweigh the risks. If the FDA accepts panel  recommendations, TAVI procedures would be available to U.S. patients.

However, CMS noted that it is aware of the high stroke and death rates associated with TAVI, and said that it remains concerned about adverse events that may occur, particularly when the procedure is performed by less experienced operators. Rates of stroke and death at 30 days were 6.7 percent and 5 percent, respectively, for those who received TAVI. At one year, these rates were 10.6 percent and 30.7 percent, CMS reported.”

As readers know; here at Cartagena Surgery – we’ve advised caution for the time being – until we have more long-term outcome data on transcatheter aortic valves.

However, after much consideration, and discussion with other people both in and outside the field of cardiac surgery – I have decided that I will begin interviewing and bringing more information about the procedure and providers performing this procedure in the USA.  Ultimately, while I may personally, (and professionally) feel that the TAVI procedure has not undergoing sufficient rigorous testing for my patients – I do not want to withhold information from them.

So, I have started writing and contacting providers to obtain more information about the physicians and medical centers performing this procedure. I will discuss these providers further in future posts.

Long-term outcomes with TAVI

As many readers know, I advise caution to patients prior to pursuing TAVI (or transcatheter aortic valve implantation, primarily because there is no long-term data on durability or long-term effects.

One of these days, I may have to eat my words – and when that day comes; I will be happy to do so (and will do it with a 14-point font).  But that day is not today.

As reported by Reed Miller over at Heartwire, there are the first results of a very small Canadian study with average follow-up 3.7 years after implantation..  Unfortunately, its way too small of a sample – and mean follow-up falls short of the five-year mark.

But given the rate of implantation in Europe (Germany, in particular) and the fact that these valves are used in younger patients over there – we should have some large (thousands of patients enrolled) studies with five-year data in just a year or two.. One of two well designed studies with a large study population would sure make a lot of us over here (in the USA) feel a lot more comfortable about the safety and efficacy of these devices in our patients.

Now, I bet most of you have gotten pretty good at picking through these Heartwire articles to get to the bit of truth inside – and the experts quoted here do a much better job at providing straight forward answers (unlike the cast of characters quoted for many of the articles regarding the stent scandals.)

(I’ll re-post below so you can see for yourself.)  I’ve also included links to our little collection of TAVI articles here – or the ‘TAVI library” for first-time readers to catch up.

1.  Aortic Stenosis – more patients need surgery  – for some background on the issue (more articles on Aortic stenosis under cardiology)

2.  TAVI  – ‘a new stent scenario’ – discussing concerns with the widespread adoption of this therapy

3.  TAVI recommendations and guidelines –  the most recent established US guidelines for therapy

4.  TAVI – an overview – getting back to the basics

5.  TAVI – mortality data – this had some pretty frightening results, another reason for caution.

6. TAVI and FDA approval: what does it mean? – talking about the implications of FDA approval, and the history of FDA approval of medical devices.

CoreValve TAVI maintains durability out to four years in small study

(Reed Miller)

[Bold type from original article]

Paris, France – The longest follow-up of patients implanted with the CoreValve (Medtronic) transcatheter aortic-valve implantation (TAVI) device presented so far suggests that it is reliable and durable in high-risk patients, according to the study investigators [1].

“In due time, I’m sure we will see a gradual decrease in the average patient age, treating patients with less comorbidity than was done in the beginning, strengthened by these types of results showing the durability of the implants,” study lead-investigator Dr Peter den Heijer (Amphia Hospital, Breda, the Netherlands) told heartwire.

Here at the European Society of Cardiology 2011 Congress, den Heijer presented long-term follow-up results from 52 patients implanted with the second-generation version of CoreValve in 2005 and 2006 in Europe and Canada. All of the patients in the study were at least 80 years old with a logistic EuroSCORE over 20 or over 65 years old with at least one high-risk comorbidity. All of the patients had severe aortic stenosis and an aortic-valve annulus diameter between 20 mm and 24 mm. Two-thirds of the patients had NYHA class 3 heart failure and almost 20% had class 4 heart failure.

Four-year follow-up data was collected on 20 patients, but 26 patients died, including 13 cardiac deaths. Overall survival was 58.5% at two years and 45.1% at four years. At four years, the surviving patients showed significant improvement in heart-failure symptoms, with 61% in class 1 heart failure and 22% in class 2. Nearly a third of patients showed grade 2 or 3 aortic regurgitation at baseline, but after four years 57% showed no regurgitation and 43% showed grade 1 regurgitation. The mean valve gradient decreased from 41 mm Hg at baseline to 12 mm Hg at 30 days and 10 mm Hg at four years.

There were no strokes reported in the study population between three months and four years and no frame fractures, valve migrations, valve endocarditis, or structural valve deteriorations leading to stenosis or regurgitation. “That’s important, because the goal of this treatment is to provide patients with severe aortic stenosis, a severely life-limiting disease, with a better prognosis, and it appears to be not at all hampered by the structure of the valve,” den Heijer told heartwire.

In a 70-patient study by Dr Ronen Gurvitch (University of British Columbia, Vancouver) colleagues, the Sapien (Edwards Lifesciences) transcatheter aortic valve showed no structural valvular deterioration, stent fracture, deformation, or valve migration over a mean follow-up of 3.7 years [2].

CoreValve is available in Europe and is being tested in a major US clinical trial that Medtronic says will be completed in 2012. The FDA is expected to approve Edward’s Sapien TAVI device soon, following a positive appraisal by its advisory committee.

Still much too early to assess long-term TAVI results

Surgeon Dr Craig Miller (Stanford University, CA), one of the investigators of the pivotal PARTNER trial of Sapien, told heartwire that while the four-year results with CoreValve are “decent,” the clinical community will “need much larger numbers of patients followed at two, three, and four years for the hemodynamics to mean much.”

PARTNER investigator Dr Michael Mack (Medical City Dallas Hospital, TX) told heartwire, “Although it’s reassuring that there are now results out to four years and there’s no sign of structural valve deterioration, it really adds minimal information to what we know already.

“There’s only 20 patients alive at four years, so how do you know what happened to the other 30 patients [in the trial]? Some died of cardiac death and some died of unknown causes. How do you know they didn’t die of structural valve deterioration?” he said. “A better way of doing this study for all aspects is that all the information should be on matched patients.”

Mack said that the real long-term durability of transcatheter valves will become more clear with more data from the SOURCE registry and the long-term follow-up of PARTNER trial, which will include annual core-lab-adjudicated echocardiography follow-up out to five years.

In an email to heartwire, Dr Grayson Wheatley (Arizona Heart Institute, Phoenix) pointed out that although the study had a high percentage of cardiac-related deaths, the arrhythmia-related deaths were a smaller proportion than in some other recent studies. But Mack and Wheatley also pointed out that because there was no echocardiographic core lab in this study, the functional assessments of the valve may not have been always accurate.

Wheatley also pointed out that this study used an older version of the CoreValve, so “this study doesn’t relate too well to real-world use of the CoreValve due to new design changes in the valve system, but it does show that, in general, TAVI procedures can be used in high-risk cardiac patients and that there will be long-term survivors.”


TAVI overseas –

As mentioned above, TAVI has rapidly been implemented in Europe.  Latin American medicine has begun to embrace this emerging technology as well.  In fact, US physicians are travelling outside the country to perform this procedure on their patients (since it’s not FDA approved.)

From a statement by the University of Miami Medical School – International Medicine Institute: [verbatim]

“New Technology Treats Aortic Heart Valve Disease Without Surgery

 At 86, Dr. Isaac Hariton is back to walking three miles a day since getting a new aortic valve this past June. To avoid surgery, this retired surgeon traveled to Cali, Columbia, for his procedure.  Hariton’s doctor is Eduardo de Marchena from UHealth – University of Miami Health System, who traveled with him to implant a valve not FDA approved for use in this country.”