Skip Navigation



European Heart Journal Advance Access published online on March 3, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn073
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
29/6/810    most recent
ehn073v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Nordmeyer, J.
Right arrow Articles by Bonhoeffer, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nordmeyer, J.
Right arrow Articles by Bonhoeffer, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Percutaneous pulmonary valve-in-valve implantation: a successful treatment concept for early device failure

Johannes Nordmeyer1, Louise Coats1, Philipp Lurz1, Twin-Yen Lee1, Graham Derrick1, Philipp Rees1, Seamus Cullen2, Andrew M. Taylor1, Sachin Khambadkone1 and Philipp Bonhoeffer1,*

1 Cardiothoracic Unit, UCL Institute of Child Health and Great Ormond Street Hospital for Children, London WC1N 3JH, UK
2 The Heart Hospital, London, UK

Received 22 September 2007; revised 19 December 2007; accepted 31 January 2008.

* Corresponding author. Tel: +44 20 7813 8106, Fax: +44 20 7813 8262, Email: bonhop{at}gosh.nhs.uk


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Funding
 References
 
Aims: Percutaneous pulmonary valve implantation (PPVI) is now an accepted treatment strategy for right ventricular (RV) outflow tract (RVOT) dysfunction in many European Heart Centres. We analysed the efficacy of repeat PPVI as a treatment modality for early device failure.

Methods and results: Twenty patients underwent repeat PPVI for RVOT obstruction because of early device failure (‘Hammock effect’, ‘Hammock-like effect’, stent fracture, residual stenosis). Repeat PPVI was feasible in all patients with no procedural complications. Following implantation of a second device, catheter-measured RVOT gradient and RV systolic pressure fell significantly (RVOT gradient: 46.1 ± 3.9 to 18.1 ± 2.4 mmHg, P < 0.001; RVSP: 70.9 ± 4.8 to 46.1 ± 2.6 mmHg, P < 0.001), in all but one patient (15 years, male, common arterial trunk, 11.5 mm homograft). During follow-up, four of 20 required re-intervention [third PPVI for stent fracture (n = 2), device explantation: external compression by the sternum (n = 1), endocarditis (n = 1)], and one of the 20 is awaiting surgical management. In the remainder, second PPVI resulted in a sustained improvement in haemodynamics with a mean follow-up of 10.9 ± 3.0 months. In this series, the probability of freedom from re-intervention at 2 years was higher after second PPVI when compared with the index procedure (89.4 vs. 20.0%, P < 0.001).

Conclusion: Repeat PPVI is an effective treatment for early device failure in defined conditions and leads to improved freedom from re-intervention.

Key Words: Catheterization • Percutaneous pulmonary valve • Congenital heart disease


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Funding
 References
 
Percutaneous pulmonary valve implantation (PPVI) has been recently introduced into routine clinical practice in many European Heart Centres as an effective treatment for right ventricular (RV) outflow tract (RVOT) dysfunction in patients with repaired congenital heart disease.1–3 However, to preserve the physiological benefits of this procedure, it is essential that device integrity is maintained. In our experience, we encountered early device failures4 that led to recurrent RVOT dysfunction. In these circumstances, it is clinically important to understand the underlying mechanisms of recurrent RVOT dysfunction, re-intervention criteria, and potential treatment options to restore adequate RV loading conditions.

We report the concept of repeat PPVI as a viable treatment modality to help relieve recurrent RVOT dysfunction because of early device failure.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Funding
 References
 
Study population
Between September 2000 and July 2007, of the 173 patients who underwent PPVI at Hôpital Necker Enfants Malades (Paris, France), Great Ormond Street Hospital for Children, The Heart Hospital and Harley Street Clinic (London, UK), 20 patients underwent a repeat PPVI procedure (Table 1) and were retrospectively reviewed. The Ethics committees at the above institutions approved the study protocol and written informed consent was obtained from patients and parents as appropriate.


View this table:
[in this window]
[in a new window]

  		Table 1 Characteristics of patients who underwent second percutaneous pulmonary valve implantation (PPVI)

 
Clinical assessment
The study protocol included echocardiography and chest X-ray immediately after PPVI and during structured follow-up at 1, 3, 6 months, and 1 year and yearly thereafter. Echocardiography (VIVID 7, GE, Medical Systems, Milwaukee, WI, USA) was performed to estimate the RVOT gradient and the RV systolic pressure (RVSP, calculated from RV–RA pressure gradient without the addition of RA pressure). Colour-flow mapping of the RVOT and branch pulmonary arteries were used to grade the degree of regurgitation (0 = absent; 1 = trivial; 2 = mild; 3 = moderate, and 4 = severe pulmonary regurgitation). Chest X-ray was used to screen for structural integrity of the stent.

Results from cardiopulmonary exercise testing (CPEX), which was performed pre- and post-implantation of a second device, were available for review in 14 of the 20 patients. In brief, a ramp protocol was performed on a mechanically braked bicycle ergometer with respiratory gas exchange analysis (Ergoline 900 Medgraphics, St Paul, MN, USA) as described previously.2,3 Peak oxygen uptake (MVO2) was derived from respiratory gas analysis during maximal exercise testing. Heart rate, blood pressure, and oxygen saturation were monitored in all subjects for the duration of the test.

Re-intervention criteria
Patients were considered for second PPVI if they re-met the indication criteria for the index PPVI. This included RV hypertension with outflow tract obstruction (RV pressure-to-systemic pressure ratio ≥0.66), significant pulmonary insufficiency, RV dilatation, or RV failure. The procedure for repeat PPVI did not differ from that of index PPVI as described previously.1,2 In cases of evident external constraints that led to a significant increase in RVOT gradient (e.g. 18 mm Hancock conduit in a growing child), repeat PPVI was deferred and elective surgery was performed.

Statistical analysis
Data are expressed as mean ± SEM, unless otherwise specified. One of the 20 patients was excluded from comparative statistics, as the second PPVI was performed at the same session as the index procedure. Two paired samples were analysed with paired Student's t-test or Wilcoxon-matched pairs test where appropriate. Multiple comparisons were performed with repeated measures of ANOVA and subsequent post hoc analysis (Bonferroni correction) where appropriate. Fisher's exact test was used to compare categorical data in a 2 x 2 contingency table. {chi}2 test for independence was used to compare the degree of pulmonary regurgitation between pre- and post-second PPVI and latest follow-up, respectively. Probability of freedom from re-intervention was obtained using Kaplan–Meier plots. Statistical significance was inferred when P < 0.05. Statistical testing and data analysis were performed with SPSS version 11 (SPSS Inc., Chicago, IL, USA) and GraphPad InStat 3 Demo (Graphpad Software, San Diego, CA, USA).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Funding
 References
 
Baseline characteristics
Twenty patients received second PPVI [median age: 18 years (9–38); median weight: 60 kg (24–98); median NYHA functional class: II (I–III)]. In all patients, the indication for second PPVI was RV hypertension because of RVOT obstruction (n = 1, measured invasively at the index procedure; n = 19, detected by echocardiography during follow-up). The RVOT obstruction was caused by early device failure (Table 1) resulting from ‘Hammock effect’ (n = 4, venous wall hangs into the stent lumen, Figure 1A), ‘Hammock-like effect’ (n = 3, lumen loss of unknown origin), stent fracture (n = 9), and residual stenosis (n = 4).


Figure 1
View larger version (63K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 1 (A) Recurrent right ventricular outflow tract obstruction because of ‘Hammock effect’ (black arrows). (B) Delivery of second percutaneous pulmonary valve implantation (PPVI) within the first with Balloon-in-Balloon (BiB) delivery system. (C) Angiographic result following deployment of second PPVI.

 
No patient in this series required a second PPVI for recurrent pulmonary regurgitation (Table 2), whereas the index procedure was performed for significant pulmonary regurgitation in nine of the 20 patients.


View this table:
[in this window]
[in a new window]

  		Table 2 Echocardiographic follow-up

 
Procedural details
Second PPVI was performed at a mean of 15.9 ± 2.9 months (0 days–3.6 years) following the index procedure (Figure Figures 1A–C). Second PPVI was feasible in all patients with no procedural complications. The procedure time was comparable to the index procedure (second PPVI: 79 ± 9 min vs. index PPVI: 89 ± 9 min, P = 0.45).

Pre-stenting with bare-metal stents (Max LD, EV3, Plymouth, MN, USA) was used more often during second PPVI when compared with index procedure (second PPVI: 12/20 vs. index PPVI: 2/20, P < 0.01).

Haemodynamics and functional data
Catheter-measured RVOT gradient and RVSP fell significantly (RVOT gradient: 46.1 ± 3.9 to 18.1 ± 2.4 mmHg, P < 0.001; RVSP: 70.9 ± 4.8 to 46.1 ± 2.6 mmHg, P < 0.001), in all but one patient (15 years, male, common arterial trunk, 11.5 mm homograft) following second PPVI.

The mean RV-to-systemic pressure ratio was lower after the second PPVI when compared with post-index procedure (second PPVI: 0.45 ± 0.02 vs. index PPVI: 0.52 ± 0.02, P < 0.05, Figure 2A).


Figure 2
View larger version (18K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 2 (A) The mean RV-to-systemic pressure ratio was lower post-second percutaneous pulmonary valve implantation (PPVI) when compared with post-index procedure (second PPVI: 0.45 ± 0.02 vs. index PPVI: 0.52 ± 0.02, P < 0.05). (B) Following the implantation of a second device, peak oxygen uptake increased significantly (26.4 ± 1.6 to 29.3 ± 1.9 mL/kg/min, P < 0.05).

 
On CPEX testing, MVO2 increased significantly following placement of a second device (26.4 ± 1.6 to 29.3 ± 1.9 mL/kg/min, P < 0.05, Table 1, Figure 2B).

Follow-up
During follow-up, four of the 20 (20%) patients had further events. Two patients with a good initial result from second PPVI developed recurrent RVOT obstruction because of stent fractures and were treated with third PPVI at 3 years. Both patients received bare-metal stents prior to third PPVI (three stents and one stent, respectively). One patient with severe external compression of the RVOT conduit, which was identified prior to second PPVI, had a good initial result after second PPVI, but recurrence of RVOT obstruction led to explantation at 1 year. One patient developed endocarditis and the valve was explanted at 6 months. In this series, the probability of freedom from re-intervention at 2 years was higher after second PPVI when compared with the index procedure in the same cohort (89.4 vs. 20.0%, P < 0.001, Figure 3A). Furthermore, the probability of freedom from re-intervention in the repeat PPVI population was not significantly different from the index PPVI in the entire cohort of 173 patients studied (P = 0.39, Figure 3B).


Figure 3
View larger version (15K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 3 (A) The probability of freedom from re-intervention at 2 years was higher after second percutaneous pulmonary valve implantation (PPVI) when compared with the index procedure (89.4 vs. 20.0%, P < 0.001). (B) The probability of freedom from re-intervention in the repeat PPVI population was not significantly different from the index PPVI in the entire cohort of 173 patients studied (P = 0.39).

 
The one patient with sustained elevation in RVOT gradient after second PPVI had a small conduit (11.5 mm) in place after repair of the common arterial trunk, which could be dilated to a maximum diameter of 15 mm at the time of index procedure with a good early haemodynamic outcome (RVOT gradients, 22 mmHg). During the course of follow-up, he had a substantial growth spurt (BSA: from 1.12 to 1.48 m2), which led to an increasing ‘patient-prosthesis’ mismatch resulting in a progressive increase in RVOT gradient. During the second PPVI (even after pre-stenting with a bare-metal stent), there was no further gain in RVOT diameter. Thus, a residual, significant gradient persists and this patient is now awaiting surgical conduit revision.

In all other patients (15/20) there was sustained improvement at latest follow-up (10.9 ± 3.0 months) when compared with immediate post-procedural results. This was demonstrated in a haemodynamic data assessed by echocardiography, which also showed preserved pulmonary valve competence (Table 2).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Funding
 References
 
We have demonstrated that repeat PPVI is an effective treatment strategy for early device failure and prolongs the freedom from re-intervention for RVOT dysfunction. Furthermore, our experience constitutes the first clinical application of a valve-in-valve concept in the fast growing field of percutaneous trans-catheter heart valve implantation.

In our early experience with PPVI, all patients with device failure were subjected to re-operation with explantation of the device and insertion of a new conduit. However, the first repeat PPVI was performed as a ‘rescue’ in case No. 12 of our entire clinical experience, when there was an acute severe residual stenosis because of ‘Hammock effect’2 after the index PPV was implanted. This established the initial proof of concept for repeat PPVI and led us to investigate the elective use of this strategy for device failure.

To date, the only haemodynamic indication for re-intervention in the PPVI population has been residual or recurrent RVOT obstruction. This was either because of device-related factors such as ‘Hammock effect’—resulting from early design imperfection—or stent fracture,4 or patient-related factors where RVOT characteristics prevented the PPVI reaching its intended diameter owing to external constraints (e.g. retro-sternal conduits).

Repeat PPVI provided an effective treatment for re-stenosis related to device failure (e.g. ‘Hammock effect’ and stent fractures) with comparable procedure times between the index and repeat procedures. Importantly, there was a significantly lower RV-to-systemic pressure ratio post-second PPVI and a higher probability of freedom from re-intervention when compared with the index procedure. Furthermore, the re-intervention rate in the repeat PPVI population was similar to the entire cohort, which suggests a comparable mid-term performance of these procedures. In the repeat PPVI population, who probably has a substrate for device failure, this is likely to be related to enhanced radial force because of both the frequent use of pre-stenting with bare-metal stents and the placement of the second device. As a follow-up consideration, there were no surgical problems with the explantation of the PPVI device, even in the context of repeat PPVI. Therefore, we do not believe that multiple stents in the RVOT add to the complexity of re-operations.

However, the patient-related factors (e.g. small conduits and those compressed by severe external constraints) do not represent a favourable substrate for repeat PPVI because of the failure to gain effective outflow dimensions. In these circumstances, surgical management with insertion of a good-sized RV-to-PA conduit (18–22 mm) might be preferable. With this strategy, surgery could provide a future platform for ‘de novo’ PPVI if required.

In our patient population, the only mechanism leading to recurrence of pulmonary regurgitation after PPVI was endocarditis. Although we did not see it in our experience, there is no reason to believe that degeneration of PPVI leaflets will not occur during the process of tissue ageing, as with other biological valves,5 and eventually lead to late device failure. Repeat PPVI may represent an effective re-intervention strategy in this scenario as the RVOT characteristics would remain favourable. This could lead to a significant reduction in the cumulative surgical burden in a significant proportion of patients after PPVI, and in some, may defer RVOT surgery lifelong. However, if the late failure occurs because of tissue in-growth and severe calcification of the valve leaflets, the change in RVOT characteristics may have to be treated differently.

The feasibility of treating selective causes of PPVI failure with a repeat procedure further adds to the benefit by prolonging RVOT conduit life and preserving favourable RV loading conditions.6–9 This is of particular importance as many patients with congenital heart disease are reluctant to undergo multiple re-operations.

Study limitations
All follow-up investigations were performed and read in a non-blinded fashion. Although our study provides proof of concept for repeat PPVI as treatment for early device failure, its mid- and long-term performance and utility for late device failure remains to be investigated.

Conclusions and clinical implications
In our series, repeat PPVI was an effective treatment for early device failure in defined conditions and led to improved freedom from re-intervention. This further adds to the benefits of PPVI in the life-time management of RVOT dysfunction.

Conflict of interest: L.C. received a Junior Fellowship from the British Heart Foundation (BHF, London, UK) and honoraria from Medtronic Inc. (Minneapolis, USA). A.M.T. is funded by the Higher Education Funding Council for England (HEFCE) and is consultant to Medtronic Inc. S.K. reports honoraria from Medtronic Inc. and is consultant to Medtronic Inc. P.B. received a BHF Programme Grant (RG/03/006), honoraria from Medtronic Inc., is a consultant to Medtronic Inc. and has ownership interest in Melody Valve (Medtronic Inc.). All other authors report no conflicts of interest.


   Funding
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
References
 
British Heart Foundation (RG/03/006 to P.B.).


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 References
 

  1. Bonhoeffer P, Boudjemline Y, Qureshi SA, Le Bidois J, Iserin L, Acar P, Merckx J, Kachaner J, Sidi D. Percutaneous insertion of the pulmonary valve. J Am Coll Cardiol (2002) 39:1664–1669.[Abstract/Free Full Text]
  2. Khambadkone S, Coats L, Taylor AM, Boudjemline Y, Derrick G, Tsang V, Cooper J, Muthurangu V, Hegde SR, Razavi RS, Pellerin D, Deanfield J, Bonhoeffer P. Transcatheter pulmonary valve implantation in humans. Initial results in 59 consecutive patients. Circulation (2005) 112:1189–1197.[Abstract/Free Full Text]
  3. Coats L, Khambadkone S, Derrick G, Sridharan S, Schievano S, Mist B, Jones R, Deanfield JE, Pellerin D, Bonhoeffer P, Taylor AM. Physiological and clinical consequences of relief of right ventricular outflow tract obstruction late after repair of congenital heart defects. Circulation (2006) 113:2037–2044.[Abstract/Free Full Text]
  4. Nordmeyer J, Khambadkone S, Coats L, Schievano S, Lurz P, Parenzan G, Taylor AM, Lock JE, Bonhoeffer P. Risk stratification, systematic classification, and anticipatory management strategies of stent fractures after percutaneous pulmonary valve implantation. Circulation (2007) 115:1392–1397.[Abstract/Free Full Text]
  5. Tweddell JS, Pelech AN, Frommelt PC, Mussatto KA, Wyman JD, Fedderly RT, Berger S, Frommelt MA, Lewis DA, Friedberg DZ, Thomas JP Jr, Sachdeva R, Litwin SB. Factors affecting longevity of homograft valves used in right ventricular outflow tract reconstruction for congenital heart disease. Circulation (2000) 102(Suppl. 3):III130–5.[Medline]
  6. Therrien J, Siu SC, McLaughlin PR, Liu PP, Williams WG, Webb GD. Pulmonary valve replacement in adults late after repair of tetralogy of fallot: are we operating too late? J Am Coll Cardiol (2001) 37:2008–2009.[Free Full Text]
  7. Warner KG, O'Brien PK, Rhodes J, Kaur A, Robinson DA, Payne DD. Expanding the indications for pulmonary valve replacement after repair of tetralogy of fallot. Ann Thorac Surg (2003) 76:1066–1072.[Abstract/Free Full Text]
  8. Geva T. Indications and timing of pulmonary valve replacement after tetralogy of fallot repair. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu (2006) 11–22.
  9. Therrien J, Marx GR, Gatzoulis MA. Late problems in tetralogy of Fallot—recognition, management, and prevention. Cardiol Clin (2002) 20:395–404.[CrossRef][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
29/6/810    most recent
ehn073v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Nordmeyer, J.
Right arrow Articles by Bonhoeffer, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nordmeyer, J.
Right arrow Articles by Bonhoeffer, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?