Are the current guidelines for performing sports with an ICD too restrictive?

March 2016Br J Cardiol 2016;23:16–20doi:10.5837/bjc.2016.008 Leave a comment

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Authors: Theresia A M Backhuijs, Hilde Joosten, Pieter Zanen, Hendrik M Nathoe, Mathias Meine, Pieter A Doevendans, Frank J G Backx, Rienk Rienks

Current guidelines recommend against vigorous sports for all patients with an implantable cardioverter defibrillator (ICD). In this study, we established the risk of life-threatening arrhythmias and shocks in patients with an ICD participating in sports.

In this single-centre, cohort survey with 71 patients (59% male) ≤40 years old at ICD implantation and with a left ventricular ejection fraction (LVEF) ≥35%, 16 patients were defined as athlete (exercise ≥5 hours per week). Sports-related and clinical data were obtained using questionnaires and medical records. Median age was 38 years (19–53 years). Median follow-up period was 67 months (11–249 months). Idiopathic ventricular fibrillation (VF) was the most frequent indication (20%) for implantation. There were 22 patients (31%) who experienced 127 shock episodes, of which 112 were appropriate: 15% of shocks occurred during physical exercise. Shocks did not occur more frequently in athletes (25%) compared with non-athletes (33%, p=0.760). Intensity of exercise and appropriateness of shocks were not associated.

In conclusion, we found no evidence that participation in sports contributed to the risk of life-threatening arrhythmias and (in)appropriate ICD shocks in patients with an ICD. In individual cases, the advice to participate in sports could be more lenient compared with current guidelines.

Introduction

An implantable cardioverter defibrillator (ICD) is used for primary and secondary prophylaxis in the treatment of life-threatening arrhythmia. Guidelines for ICD patients, originally published in 2005, advise against any competitive sports more vigorous than ‘Class IA’ activities such as bowling or golf.¹ American College of Cardiology (ACC)/American Heart Association (AHA)/European Society of Cardiology (ESC) embraced this advice stating “for legal and ethical reasons athletes receiving cardiovascular drugs and devices such as pacemakers and ICDs are generally not allowed to participate in high-grade competition.”² For leisure-time sports, Heidbuchel et al. allow exercise from six weeks after an ICD implantation with assessment of expected maximal sinus rate and/or preponderance for atrial fibrillation with prophylactic institution of antiarrhythmic or bradycardic therapy.³

The postulated risks on which these restrictions are based, are, first, increased risk of defibrillator shocks, both appropriate and inappropriate, and, second, potential failure of a shock to convert a life-threatening arrhythmia. Competing athletes have an increased adrenergic tone, which may reduce the efficacy of defibrillator shocks. Third, in some sports, such as weightlifting and golf, repetitive arm-motion can induce excessive stress on lead systems. Contact sports have a risk of device and lead damage.⁴ Finally, adverse events have been reported due to arrhythmia or shock during sports participation, for instance falling from a bicycle while having an arrhythmia treated by an ICD shock.⁴

Young athletes with an ICD and preserved left ventricular function are often caught between the passion to continue their sport and the guidelines, which are felt to be too restrictive. At the heart of this dilemma is a lack of evidence about the natural history of athletes with an ICD participating in (competitive) sports. As there are no prospective data in elite athletes with ICDs, the current guidelines are based on realistic, albeit largely theoretical, considerations without the essential level-of-evidence classifications. Evidence is needed to guide these patients, their families and physicians to make an informed decision about sports participation.

To address this issue, we performed a retrospective single-centre cohort survey in which the primary end points were to establish:

Whether participating in sports for patients with an ICD is related to an increased risk of untreatable ventricular arrhythmias.
Whether athletes with an ICD received more frequently appropriate shocks compared with non-athletes.

Additionally, the following secondary end points were addressed:

Is the intensity level of the sport related to the initiation of ICD shocks?
Is there an association between the indication for ICD implantation (diagnosis, primary or secondary prophylaxis) and the occurrence of (in)appropriate shocks?
Are certain sport activities more likely to induce life-threatening arrhythmias?
What is the risk of damage to the cardioverter device during physical exercise and does this result in an increased risk of receiving (in)appropriate shocks?

Materials and methods

For this cohort-survey we analysed all patients from our ICD database over the period of 1992 to 2010. We included all patients younger than 40 years of age with a preserved left ventricular ejection fraction (LVEF >35%) at implantation of the device. Ninety-five patients with an ICD were included. LVEF was assessed by ultrasound, radionuclide heart scan or magnetic resonance imaging (MRI). All participants were interviewed via telephone using a questionnaire (available on request). Sports performed by the participants before and after implantation of the device were classified using the Bethesda Classification of Sports.¹ Other descriptive variables obtained from the questionnaires, such as prevalence of both appropriate and inappropriate ICD shocks, were categorised in groups and compared with a similar group of patients who did not experience shocks.

To define ‘sport’ we used the World Health Organization’s definition: “Physical activity with a described functional purpose, e.g. competition, practicing for competition, improving physical health. This includes practice and training as well as pre-event (e.g. taping, dressing), warm-up, cool down, and post-event (e.g. showering, dressing) activities. Travel to and from the event or activity is not included.”⁵

As an athlete we classified those participants who exercised ≥5 hours per week on a structural basis, in analogy of Drezner et al.⁶

An ‘appropriate shock’ was considered to be a shock delivered by the ICD because of a life-threatening arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF]). An ‘inappropriate shock’ was considered to be a shock delivered by the ICD because of any other reason, for instance supraventricular tachycardia or malsensing. To decide whether the shock was appropriate, the treating physician’s diagnosis after interrogation of the ICD was used.

Table 1. Demographics of study population

All data were entered into a computerised database. Descriptive statistics were provided, and cross-tabulation and subsequent Chi-square tests were performed for categorical and dichotomous variables. The study population was categorised in groups: athletes versus non-athletes. Variables were untreatable arrhythmias and appropriate shocks for analysis of primary end points. To analyse whether the intensity level of the sport relates to the initiation of ICD shocks, we categorised our study population in groups using the Bethesda classification of sports.¹ To analyse whether there is an association between the indication for implantation of an ICD and the occurrence of shocks, we categorised our study population in groups using International Classification of Diseases, version 10. The same test was performed categorising the study population in groups according to primary or secondary prophylaxis. To analyse whether certain sport activities are more likely to induce life-threatening arrhythmias we categorised the study population in groups according to sport: contact sports, arm sports, swimming, fitness, endurance sports, horseback riding, other sports. The variable in this case was untreatable arrhythmias. To assess the risk of damage to the ICD device we used the same groups as in the third question, variable in this case was damage to ICD device.

Data were analysed using SPSS version 20.0 and a p value <0.05 was considered as significant.

Results

A total of 95 patients fulfilled the inclusion criteria, of whom, 19 were lost to follow-up and two patients did not want to participate. The patients who were lost to follow-up came to our hospital for ICD implantation only. After the operation they went back to their own cardiologist’s practice for follow-up. These patients must have moved in the meantime, since the registered contact details no longer worked. Three patients died during the follow-up period because of non-related causes. We did not include these three patients in our analysis because it was not possible to establish whether they would have met the criteria for an athlete.

The median age of the 71 remaining participants was 38 years (range 19–53 years). The median age at ICD implantation was 30 years (range 14–40 years). Median follow-up after implantation was 67 months (range 11–249 months). Demographic and clinical characteristics of our population are shown in table 1.

The most frequent diagnosis for ICD implantation in our study population was idiopathic VF (20%). In 62% of participants the ICD was implanted as secondary prophylaxis. Before ICD implantation the most common sports in our population were equally divided over fitness (18%), endurance (18%) and contact sports (17%). A total of 10 patients did not participate in any sport before ICD implantation. After implantation a considerable part of our population became non-athletic (29 patients) or even quit exercising (26 patients). Time spent exercising decreased after ICD implantation, from an average of 4.1 hours per week to 2.7 hours per week (table 1). The most common sports remained endurance sports and fitness. Patients participating in swimming sports before ICD implantation (n=4) all quit after implantation.

Of our study population, 70% stated that their cardiologist advised them to either quit their sport or to choose another, less vigorous type of sport according to Bethesda classification. Prudence enforced by restrictive current guidelines was the basis for this advice. Interestingly, 89% of our study population said they were confident to exercise, even after receiving a shock, although only 63% actually participated in sports in one form or another.

Primary end points

There were 22 patients (31% of study population) who experienced 127 shock episodes. Eventually, 112 (88%) of these shock episodes were shown to be appropriate (figure 1). In our study population, six individuals experienced an electrical storm, i.e. ≥3 distinct episodes of VT/VF in 24 hours (8% of our study population). In the present survey, electrical storms occurred in patients with idiopathic VF (n=3), hypertrophic cardiomyopathy (n=1), long QT syndrome (n=1) and arrhythmogenic cardiomyopathy (n=1). None of our patients with catecholaminergic polymorphic VT experienced an electrical storm, even though electrical storms are common in this cardiac condition.⁷ Two of the six persons who experienced an electrical storm had it during exercise, i.e. walking and delivering a baby. Only one of these six persons experiencing an electrical storm was classified to be an athlete.

Overall, 15% of both appropriate and inappropriate shocks occurred during exercise. Athletes did not receive shocks more frequently than non-athletes (p=0.760). ICD shocks in athletes were not more frequently appropriate nor inappropriate compared with non-athletes (p=0.501).

Secondary end points

We could not establish a relationship between receiving either appropriate or inappropriate shocks and the level of physical exercise or the kind of sports. This is due to small sample size; we didn’t perform a power analysis on secondary end points. Eleven patients received a shock during physical exercise. When classified in groups according to the Bethesda classification,¹ three patients received a shock during exercise at low intensity (VO₂max <40%) and six patients received a shock during exercise at high intensity (VO₂max >70%). One patient in this group received a shock when having sexual intercourse and one patient during delivery of a baby.

Shocks during or after high-intensity physical activity occurred in patients with idiopathic VF (n=3), hypertrophic cardiomyopathy (n=1), catecholaminergic polymorphic VT (n=1) and arrhythmia not specified (n=1). Shocks occurred during low-intensity physical activity in individuals with Brugada syndrome (n=1), arrhythmogenic cardiomyopathy (n=2) and idiopathic VF (n=2). Specific details on the 20 patients receiving either an appropriate or inappropriate shock are available on request. In this analysis, more non-athletes than athletes received a shock, both in rest and during exercise. The athletes in our study population did not experience more damage to their leads or devices than the non-athletes (p=1.000).

In a subgroup analysis, we found that receiving ICD shocks was not associated with the cardiac diagnosis (p=0.224). This was also the case for receiving appropriate shocks in relation to the cardiac diagnosis (p=0.505). Moreover, the indication (primary or secondary) for implanting the device was not associated with receiving shocks (p=0.075) nor with receiving appropriate shocks (p=0.153).

Discussion

The guidelines for cardiac patients with an ICD restrict physical activity to the level IA (meaning a low dynamic and low static component) sports, e.g. playing golf or billiards, the rationale being the fear for intractable VT/VF during more demanding sports. However, no risk stratification based on, for instance, underlying cardiac disease or LVEF has ever been made, and so one wonders whether there are subsets of patients with an ICD for which the restrictions can be eased.

In this study, we could not establish that in patients under 40 years with an ICD and a LVEF >35%, performing vigorous sports, were at greater risk of appropriate or inappropriate shocks compared with patients who did not perform these sports. This was true for all the indications (underlying cardiac disease, primary or secondary indication). So far, our study included the largest population. Due to the lack of consensus on clinically important event rates, a sample size calculation cannot be performed. The way this study was designed, the possibility of a selection bias was minimised. The population represents a cross-section of a population with an ICD not restricted by further selection of a population with a certain type or brand of cardioverter device.

The number of both appropriate and inappropriate shocks are in line with the numbers found in the literature,⁸ although it concerned patients with a reduced LVEF (<35%) after myocardial infarction. We note that our follow-up time was longer.

There are only limited data on the safety of sports in ICD patients. Lampert et al. found in 372 patients engaged in organised or high-risk sports (meaning that loss of consciousness could result in severe injury or death) that 10% received a shock, of which about half were appropriate.⁹ In a subset of 60 young patients (<21 years), from university teams engaging in competitive sports, 28% received 25 shocks, of which only half were appropriate and only two occurred during competition or practice, and six during other physical activity. There was no statistical difference in shock frequency between the competitive and the non-competitive groups.

The follow-up period of Lampert’s study was 31 months (median) with a slightly younger population (average age 33 years, median).⁹ In our study, the follow-up time was 67 months (median) with an average age of 38 years (median): our estimates are, therefore, more precise. The incidence of shocks in our study group and in the young competitive group of Lampert et al. was similar, thus, indicating a low a priori risk.⁹ Although it is tempting to speculate that the incidence of ICD shocks may not change over time in this subpopulation, this has not been established yet.

From this study, it cannot be inferred whether the underlying diagnosis must influence a decision to engage as an athlete or not, since a wide diversity of diagnoses for which the ICD was implanted was present in the cohort. However, it concerned relatively young patients with a preserved LVEF and there were no reasons, other than the ICD implantation itself and the concomitant fear of a life-threatening arrhythmia provoking an ICD shock, not to engage in sports. A reason not to engage as an athlete could be the evidence that sport indeed lowers the arrhythmia threshold. This has been described in a study with patients with arrhythmogenic right ventricular cardiomyopathy.¹⁰ A subset of patients with hypertrophic cardiomyopathy and VT/VF during exercise testing are also more at risk of VT/VF during exercise.¹¹ An association of VT/VF with exercise was found in polymorphic catecholaminergic VT and long QT syndrome type I, but not in Brugada syndrome nor idiopathic VF.¹² Although it may be inferred that exercise can provoke arrhythmias in some patients with the above-mentioned diagnoses, an athletic lifestyle does not apparently increase the risk of ICD in these categories.

We realise that the ICD implantation itself has an effect on performing sports and on the type of sports performed (figure 2). ICD patients tend to give up sports, especially contact sports or arm sports. Swimming was given up altogether. However, a lot of participants admit that they would like to do some sort of exercise but that they were advised against. Another explanation to give up sport or to choose another sport can be found in psychological factors, such as the fear to provoke an ICD shock. After ICD implantation, the most frequently performed sports were fitness and endurance sports. Some athletes participated in moderate contact sports like soccer and hockey; none played more aggressive contact sports, such as rugby or ice hockey. It is possible that damage to the ICD system would have occurred in these types of exercise. Therefore, the results from this study must be restricted to this category.

Figure 2. Main sport before and after implantable cardioverter defibrillator (ICD) implantation

A limitation of this survey is its retrospective design. Three possible sources of bias are recognised: the 19 subjects, lost to follow-up, are possibly a deviating subgroup; differences in athlete/non-athlete group characteristics as the groups were not randomised; and recall bias. To deal with the first of these we checked the underlying diagnosis and the demographics of these 19 subjects: there were no relevant differences in baseline characteristics, e.g. age, LVEF or underlying disease. We, thus, conclude that they were ‘missing at random’. When subjects are deemed to be more prone to shocks than others, the advice to stop exercising will/may be more stringent. These subjects will easily slip into the non-athlete group and show possibly a higher shock rate: this ‘increased probability’ was comparable with the shock rate in athletes, which is then also ‘higher’ as expected. At the moment, however, there are no clear objective reasons and/or diagnosis to advise stronger against sports and we judge this mechanism as improbable. The third source, recall bias, must be assumed to be present, while realising the profound effect of a shock on the subjects’ psyche. Recall bias, however, to invalidate the outcome must be unequally distributed over the athlete/non-athlete groups: when both groups suffer from the same amount of recall bias, the effects are similar and do not influence the comparison. There is no reason to assume that one group suffers from stronger recall bias.

Another possible limitation of this survey is the length of the follow-up period. Five and a half years of follow-up, on average, is a long time, however, we cannot predict whether this period is long enough to make recommendations for a patient’s lifetime. On the other hand, there is currently no study with a longer follow-up period.

Conclusion

In young patients with an ICD and with a preserved LVEF, we found no evidence that participation in sports (mainly endurance sport and fitness) contributed to the risk of life-threatening arrhythmias and
(in)appropriate ICD shocks.

The current guidelines for performing sports with an ICD may be too restrictive for some patients. Patient-tailored advice is recommended for patients who want to continue their sport activities after ICD implantation, which might include lifting the restrictions to sport beyond the IA category.

Sources of support for research

None.

Conflict of interest

None declared.

Editors’ note

Additional information showing the number of appropriate and inappropriate shock events and the diagnosis for ICD implantation is available on request. Email: [email protected]

Key messages

There is no increased risk of untreatable ventricular arrhythmias for young patients participating in sports with an implantable cardioverter defibrillator (ICD) (≤40 years old) and with a preserved left ventricular ejection fraction (LVEF)
Athletes with an ICD do not receive more frequent appropriate shocks compared with non-athletes
The intensity level of sport is not related to the occurrence of shocks
In individual cases, the advice to participate in sports could be more lenient compared with current guidelines

References

1. Maron BJ, Zipes DP. 36th Bethesda Conference: eligibility recommendations for competitive athletes with cardiovascular abnormalities. J Am Coll Cardiol 2005;45:1313–75. http://dx.doi.org/10.1016/j.jacc.2005.02.006

2. Zipes DP, Camm AJ, Borggrefe M et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Europace 2006;8:746–837. http://dx.doi.org/10.1093/europace/eul108

3. Heidbuchel H, Corrado D, Biffi A et al. Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators. Eur J Cardiovasc Prev Rehabil 2006;13:676–86. http://dx.doi.org/10.1097/01.hjr.0000239465.26132.29

4. Lampert R, Philip Saul J. Chapter 18. Athlete with a device: implantable cardioverter defibrillators and pacemakers. In: Lawless CE, ed. Sports Cardiology Essentials. Evaluation, Management and Case Studies. New York, NY: Springer, 2011. http://dx.doi.org/10.1007/978-0-387-92775-6_18

5. Valkenberg H, Schoots W, Van Nunen M et al. Handboek Epidemiologie Sportblessures, versie 4.1. Stichting Consument & Veiligheid, maart 2010.

6. Drezner JA, Fischbach P, Froelicher V et al. Normal electrocardiographic findings: recognising physiological adaptations in athletes. Br J Sports Med 2013;47:125–36. http://dx.doi.org/10.1136/bjsports-2012-092068

7. Miyake CY, Webster G, Czosek RJ et al. Efficacy of implantable cardioverter defibrillators in young patients with catecholaminergic polymorphic ventricular tachycardia: success depends on substrate. J Circ Arrhythm Electrophysiol 2013;3:579–87. http://dx.doi.org/10.1161/CIRCEP.113.000170

8. Daubert JP, Zareba W, Cannom DS et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT-II: frequency, mechanisms, predictors and survival impact. J Am Coll Cardiol 2008;51:1357–65. http://dx.doi.org/10.1016/j.jacc.2007.09.073

9. Lampert R, Olshansky B, Heidbuchel H et al. Safety of sports for athletes with implantable cardioverter-defibrillators: a prospective, multinational registry. Circulation 2013;127:2021–30. http://dx.doi.org/10.1161/CIRCULATIONAHA.112.000447

10. James CA, Bhonsale A, Tichnell C et al. Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. J Am Coll Cardiol 2013;62:1290–7. http://dx.doi.org/10.1016/j.jacc.2013.06.033

11. Gimeno JR, Tome-Esteban M, Lofiego C et al. Exercise-induced ventricular arrhythmias and risk of sudden cardiac death in patients with hypertrophic cardiomyopathy. Eur Heart J 2009;30:2599–605. http://dx.doi.org/10.1093/eurheartj/ehp327

12. Prystowsky EN, Padanilam BJ, Joshi S, Fogel RI. Ventricular arrhythmias in the absence of structural heart disease. J Am Coll Cardiol 2012;59:1733–44. http://dx.doi.org/10.1016/j.jacc.2012.01.036

Heart valve disease module 5: medical therapies for treatment of valvular heart disease

Released 1 March 2016 Expires: 01 March 2018 Programme: Heart valve disease 1 CPD/CME credit

Sponsorship Statement: This module has been sponsored by Edwards Lifesciences with an unrestricted educational grant

Designed to give healthcare professionals a clear understanding medical therapies for the treatment of valvular heart disease. It is one of several modules in our heart valve disease programme.

1 CPD/CME credit

Module originally published July 2013. Revised module released March 2016

Learning objectives

Upon completing this module, participants should be better able to:

Understand the role of disease-modifying pharmacotherapy in valvular heart disease (VHD)
Understand the role of supportive pharmacotherapy in VHD
Recognise the indications for anticoagulation in VHD
Be aware of the patient groups at high risk of developing infective endocarditis
Realise the reasons for recent changes in international guidelines which restrict antibiotic prophylaxis of endocarditis
Compare and contrast the differing recommendations for antibiotic prophylaxis of the European Society of Cardiology and the UK National Institute for Health and Clinical Excellence.

Faculty

Dr Sean Coffey, Research Fellow, Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford
Dr Bernard D Prendergast, Consultant Cardiologist, Guy’s and St Thomas’s NHS Trust, London

Accreditation

1 CPD/CME credit, 1 hour
BJC Learning has assigned one hour of CPD/CME credit to this module
The European Board for Accreditation in Cardiology (EBAC) has assigned one CME credit to this module. German participants should contact EBAC to receive a German VNR code for this course.
email: [email protected]
website: http://www.ebac-cme.org/

Produced in collaboration with:

British Heart Valve Society

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Advances in transcatheter options in the management of mitral valve disease

March 2016Br J Cardiol 2016;23:21–6doi:10.5837/bjc.2016.009 Leave a comment

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Authors: Mamta H Buch

Sponsorship Statement:

This article was commissioned by the British Journal of Cardiology on behalf of Abbott Laboratories Ltd. who provided the funding. BJC engaged Dr Mamta Buch, who received an honorarium for its writing. Abbott Laboratories had no input into the content of the article written by Dr Buch, but has reviewed the article for regulatory compliance before publication.

MitraClip® is a trademark of the Abbott Group of Companies. The product is subject to prior training requirement as per the Instructions for Use. The product is intended for use by or under the direction of an appropriately qualified medical practitioner. Prior to use, it is important to read the package insert thoroughly for instructions for use, warnings and potential complications associated with use of this device.

Current transcatheter mitral valve techniques are at the beginning of an era of innovation before their full potential is realised. The broadening of available options for mitral regurgitation (MR) reduction is welcome and transcatheter mitral valve interventions provide complementary strategies in the drive for more safe and effective therapies for patients. In this article, the evidence and indications for MitraClip^® are reviewed.

Introduction

Dr Mamta Buch, University Hospital of South Manchester NHS Foundation Trust

Mitral regurgitation (MR) is increasingly prevalent in developed countries and represents a significant cause of morbidity and mortality. It affects 24% of adults with valvular heart disease and is present in 7% of the population over the age of 75 years.^1,2 Significant MR is a complex condition and, left untreated, it leads to slow progressive deterioration. Up to 50% of patients with criteria for surgical intervention are not referred for surgery, largely due to advanced age, significant comorbidities and the presence of left ventricular (LV) dysfunction.^3,4 This unmet clinical need has fuelled innovation in transcatheter approaches for the mitral valve.

Mitral valve anatomy and function

The mitral valve structure is complex. The dynamic, saddle-shaped annulus provides fibrous continuity between the anterior mitral valve leaflet and aortic valve cusps. The leaflets are supported by a subvalvular apparatus (including the chordae tendinae and papillary muscles) and are in proximity to the aortic valve, circumflex coronary artery, coronary sinus and the conduction system. The central position of the mitral valve, with valvular and subvalvular connections in the left ventricle, helps maintain left ventricular shape and chamber contractility.⁵ Mitral valve therapy requires attention to the ‘functional anatomy’ of the mitral valve complex,^6,7 in order to avoid injury and complications.

Classification of MR and mitral valve pathology

MR is broadly classified into two main categories: primary valvular disease or organic MR (intrinsic valve lesions) and secondary or functional MR (a structurally normal mitral valve but ventricular remodelling causes downward papillary muscle displacement, leaflet tethering and annular dilatation). The Carpentier classification⁸ describes MR based on leaflet movement and provides a unifying language to describe mitral valve pathology based on echocardiographic findings (table 1). The posterior leaflet is divided into three segments or scallops: lateral P1, middle P2 and medial P3. The opposing A1, A2 and A3 segments of the larger anterior leaflet correspond to the posterior leaflet segments.

Table 1. Carpentier classification of mitral regurgitation. This functional classification originally described by Carpentier is based on the surgical aim to restore normal valve function rather than normal valve anatomy. It is categorised by the opening and closing motion of the mitral valve leaflets. The lesion abnormalities and aetiologies in relation to this classification are described. It should be noted that more than one Carpentier type may co-exist in any one individual

Indications for mitral valve surgery

Guidelines recommend surgical repair or replacement for symptomatic patients (class I) with severe MR due to a primary valvular abnormality or asymptomatic patients with severe MR and LV dysfunction or enlargement.^9,10 Surgery may also be considered an option for symptomatic patients (class IIb) with secondary (functional) MR.^9,10 Mitral valve repair, when feasible, is almost universally regarded as the preferred method of MR correction (in non-rheumatic valves) over mitral valve replacement due to the advantages of even partial preservation of subvalvular chordae.^11-14 Surgical repair techniques are defined by the patho-anatomy and physiology of MR,^15,16 and provide a tailored approach to restoring normal mitral valve function.

Surgical repair results for primary or degenerative MR are excellent in experienced centres with procedural volume.¹⁷ Secondary or functional MR (FMR) remains a surgical challenge. Data have failed to clearly demonstrate survival benefit in these patients,¹⁸ and reported recurrence rates range from 15% to 60%.^19,20 The pathophysiology of FMR is complex and the more contentious role of surgery reflects the underlying ventricular nature of the problem in a high-risk population. Only a third of patients with FMR are referred for surgery, and FMR is present in 90% of patients who are denied surgery.^21,22

Challenges of transcatheter mitral valve techniques

The first case of percutaneous mitral valve repair was performed in 2003,²³ and, yet, the clinical application of this approach has been more challenging compared with aortic valve stenosis.²⁴ The greater complexity of mitral regurgitation, and the patient heterogeneity,²⁵ presents greater challenges for the transcatheter approach, device development and, indeed, trial design.

MitraClip^®

The MitraClip^® (Abbott Vascular, Santa Clara, California, US) percutaneous repair system is the only transcatheter mitral valve therapy to undergo a pivotal randomised-controlled trial. It is based on the surgical procedure pioneered by Ottavio Alfieri in the early 1990s.²⁶ Over 30,000 patients have been treated worldwide. This technique creates a competent double orifice valve by suturing the free edges of the middle portion of the anterior leaflet (A2) to the middle portion of the posterior leaflet (P2). To improve the durability of results, the Alfieri repair is typically combined with implantation of a partial band or complete annuloplasty ring, except in cases with a severely calcified mitral annulus.²⁷

The MitraClip^® is made of a cobalt–chromium alloy and covered with polypropylene fabric to promote tissue in-growth.^28,29 It is a single-size clip device that has been used to treat patients with functional, mixed and degenerative MR. The Clip has a dual-arm structure, with grippers above the arms to assist with capture of the mitral valve leaflets and their approximation while the heart is beating.

The procedure

The procedure is approached via the femoral vein, and trans-septal access permits delivery of the catheter-based MitraClip^® device into the left atrium (figure 1). All manoeuvres are performed under transoesophageal echocardiographic (TOE) visualisation. The device is positioned directly above the regurgitant jet and advanced across the mitral valve into the left ventricle. The Clip is retracted toward the mitral valve leaflets to engage the appropriate segments of the mitral valve. The grippers are dropped and arms of the Clip are closed. If the leaflet insertion visualised on TOE is acceptable, the degree of residual MR is assessed with the Clip fully closed. If reduction is inadequate, the Clip may be released and repositioned or a second clip may be implanted. The addition of Clips is guided by, among other factors, transmitral valve diastolic gradient, as a surrogate measure for potential development of mitral stenosis. After the Clip(s) are deployed, and the delivery catheter is removed from the patient, manual compression, use of a temporary subcutaneous suture, or placement of a percutaneous suture may be used to close the femoral vein access site.

Figure 1. MitraClip® percutaneous edge-to-edge repair for mitral regurgitation. A. Mitraclip® clip at the end of the steerable delivery system. B. Illustration of the clip just below leaflets prior to grasping. C. Echocardiographic view of the open clip positioned just below leaflets. D. Three-dimensional echocardiographic view of double orifice valve

The unique features of this procedure are:

the clip is repositionable (if a decision is made not to deploy the Clip, it may be removed)
real-time echocardiographic assessment of MR reduction is obtained
it produces vertical coaptation of leaflets and is not simply an edge-to-edge repair
surgical options are preserved.

Evidence base for MitraClip^®

EVEREST II

MitraClip^® is the first percutaneous device to be compared with surgery in a randomised-controlled trial (RCT). The pivotal EVEREST II (Endovascular Valve Edge-to-Edge REpair Study) phase II RCT comprising 279 patients was completed in 2008.³⁰ It included patients with both degenerative and functional MR, although predominantly degenerative MR (73%). Surgery was superior for the primary outcome of freedom from death, surgery for mitral valve dysfunction, or ≥3+ MR. MitraClip^® was safe with only 15% of patients experiencing a major adverse event compared with 48% of surgical patients (largely composed of transfusion ≥2 units). The degree of MR reduction was greater in the surgical patients, however, important clinical indicators, including heart failure functional status (New York Heart Association, NYHA), ejection fraction, LV dimensions and quality of life (QoL), improved in both groups. Nearly 80% of patients were free from 3+ or 4+ MR after Clip placement and did not require surgery in 12-month follow-up. The majority of MitraClip^®-treated patients who required an additional procedure did so within the first six months after initial treatment.³⁰ Clinically significant cases of mitral stenosis in the MitraClip^® group was not observed.

Five-year follow-up of patients in the EVEREST II trial reported no increase in late MR recurrence compared with surgery.³¹ A good immediate result with MitraClip^® showed excellent durability of the repair (at five years). The improved NYHA class was sustained and mortality rates were not different between the treatment arms at years one or five.

The rates of re-operation, or additional MitraClip^® procedures, were no different between the two treatment groups after the first year. There did not appear to be a significant change in MR grade, ventricular function or dimension in follow-up, however, longer-term follow-up of the subset of patients with MR grade 2+ is ongoing.

Registry data

In Europe, CE mark was obtained in March 2008. ACCESS-EU (ACCESS-Europe A Two-Phase Observational Study of the MitraClip System in Europe) is a post-marketing registry of MitraClip^® patients comprising 567 patients.³² These patients were more elderly and higher surgical risk candidates than those evaluated in the EVEREST II trial. More patients had functional MR, and the anatomical characteristics of the mitral valve in 70–80% of these patients were outside the inclusion criteria stated in the EVEREST II trial.³³ Positive clinical outcomes with the Clip were still demonstrated at one year with improvements in degree of MR reduction and NYHA heart failure classification, QoL and six-minute-walk test results. Outside the USA, where Food and Drug Administration (FDA) approval has been limited to degenerative MR, and at least in Europe, this is currently the group of patients most commonly receiving MitraClip^® repair.

Systematic reviews of MitraClip^® versus surgery confirm that, while MitraClip^® is not as effective as surgery in reducing MR, it can provide clinical benefits. Munkholm-Larsen et al.³⁴ identified MitraClip^® implantation as an option in managing select high surgical risk patients with severe MR, but noted a lack of mid- to long-term data in high-risk groups. In a meta-analysis by Wan et al.³⁵ the clinical outcomes were similar despite a higher risk profile in the MitraClip^® patients compared with surgical intervention, although surgery was more effective in reducing MR in the early post-procedure period. Buzzatti et al. reported over 5.5 years of a single centre’s experience comparing MitraClip^® with surgery in octogenarians with degenerative MR.³⁶ MitraClip^® was safer, despite being applied in an older and more symptomatic population with higher burden of comorbidities. MR reduction was not as optimal as surgery, but provided reduction in symptoms. This improvement in QoL, with greater procedural safety and quicker recovery compared with surgery, as well as reduction in burden on health services, is of key relevance in managing the elderly population.

Guidelines

The European Society of Cardiology (ESC) guidelines for heart failure 2012³⁷ provide a class IIb (level of evidence C) indication for MitraClip^® in patients with both degenerative and functional MR in order to improve symptoms. Patients must be judged inoperable or at unacceptably high surgical risk, and have a life-expectancy of greater than one year. Primary MR (degenerative MR) and secondary MR (FMR) reflect two very distinct clinical groups. Patients with FMR must be on optimal medical therapy including cardiac resynchronisation therapy where appropriate.

Functional MR – an emergent indication?

There remains some skepticism, particularly with respect to heart failure patients with FMR, due to the limited data from the EVEREST II RCT,³⁰ and extrapolation from uncontrolled registry data.³⁸ MR in heart failure confers a worse prognosis,^39-41 but it has not been clear whether it is simply a marker of underlying LV muscle disease or a target for intervention.

Currently, four trials directly comparing MitraClip^® to medical therapy in patients with heart failure and MR are underway to fill the current knowledge gap; one in the USA – COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Patients Trial),⁴² and three in Europe – RESHAPE-HF (A Randomised Study of the MitraClip Device in Heart Failure Patients with Clinically Significant Functional Mitral Regurgitation), MITRA-FR (Multi-centre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation) and MATTERHORN (A Multicenter, Randomised, Controlled Study to Assess Mitral vAlve reconsTrucTion for advancEd Insufficiency of Functional or iscHaemic ORigiN).^43-45 These contemporary prospective, randomised trials will be instructive in guiding MitraClip^® implantation in FMR, or indeed, mitral valve intervention of any kind.

Patient selection

Figure 2. EVEREST II (Endovascular Valve Edge-to-Edge REpair Study) trial anatomic eligibility criteria. These criteria describe characteristics to ensure sufficient leaflet tissue for mechanical coaptation when the MitraClip® device is used. The coaptation length must be at least 2 mm. Coaptation depth must be <11 mm. If a flail leaflet exists, the flail gap must be ≤10 mm, and the flail width must be ≤15 mm

A heart team comprised of cardiac surgeon, heart failure specialist, echocardiologist and interventional cardiologist is critical to determining the most appropriate patients for intervention with MitraClip^® therapy.

Patients are assessed for clinical indication, which broadly reflects the ESC guidelines.³⁷ Evaluation may include stress echocardiography to assess for dynamic MR and cardiac magnetic resonance (CMR) imaging for viability and ischaemia testing. Technical suitability is determined by assessing the anatomical characteristics of the valve and pathology with TOE. Approximately 25% of patients referred for consideration of MitraClip^® are considered suitable, which reflects the complex nature of MR. Moderate or severe tricuspid regurgitation and pulmonary hypertension are poor predictors of outcome with respect to NYHA functional class and re-hospitalisation with heart failure.

The EVEREST trial included stringent anatomical criteria that focused on the middle, A2–P2, segment of the valve.³⁰ The anatomic eligibility criteria are shown in figure 2.⁴⁶ The European experience suggests technical feasibility in a more complex group of patients can be achieved with an increase in the learning curve.³² Nevertheless, adverse anatomical features exist and recognition of these limitations is important to ensure optimal outcomes.

Table 2 provides a summary of the clinical and anatomical criteria.

Table 2. Clinical and anatomical selection criteria for MitraClip® therapy. The EVEREST (Endovascular Valve Edge-to-Edge REpair Study) data were based on ‘ideal’, rigorous anatomic criteria. Registry experience suggest more complex pathology may be treated, and are described here as ‘acceptable’ and ‘unsuitable’ criteria

MitraClip^® in England

Although the technology has been commercially available in Europe since 2008, National Health Service (NHS) England only commissioned this technology for evaluation in 2014. The Commissioning through Evaluation (CtE) programme⁴⁷ supports a small number of procedures to be funded within a limited number of selected centres and within a limited time frame. Three centres in the country were selected to deliver this therapy:

Royal Brompton and Harefield Hospitals (RBHT), London
University Hospital of Bristol (UHB)
University Hospital of South Manchester (UHSM).

Each was commissioned to treat 40 patients per year. Associated data collection will provide evidence on the relative clinical- and cost-effectiveness of the procedure, which will be used to inform a commissioning policy decision. The MitraClip^® registry is managed by NICOR (National Institute for Cardiovascular Outcomes Research), with the National Institute for Health and Care Excellence (NICE) supporting NHS England in the evaluation of the scheme.

Links to the three centres can be found below. These will direct you to dedicated proformas (which function as stand-alone referral letters or may be used to guide referral details) with coordinator contact details for the three centres:

Summary

MitraClip^® offers a safe and effective percutaneous strategy for high surgical risk or inoperable patients. Comorbidity, such as frailty, severe lung disease or multi-organ decline, should be recognised as key limitations in achieving positive outcomes. Primary MR and secondary MR should be recognised as two distinct patient populations with specific approaches to diagnosis and treatment. Secondary MR reflects a ventricular problem that should primarily be managed via optimisation of medical therapy and cardiac resynchronisation therapy (CRT), where indicated. Registry data, however, suggest FMR as a target for intervention. RCTs will be crucial to informing whether this expansion in indication is supported for mitral valve therapies of any kind. The importance of timely intervention, before an irreversible decline in LV remodelling and pulmonary hypertension ensues, may focus attention on earlier intervention, if safe and effective outcomes are shown to be durable beyond five years.

Percutaneous strategies presently limit repair options to a single point of intervention. The MR reduction and clinical improvements observed with MitraClip^® without annuloplasty may reflect the advantages of the vertical coaptation produced with the MitraClip^®. Nevertheless, longer follow-up of patients with residual grade 2 MR in particular, will be important. Development of percutaneous direct annuloplasty technologies might offer the potential to enhance long-term outcomes.

Conclusion

Current transcatheter mitral valve techniques are at the beginning of an era of innovation before their full potential is realised. The broadening of available options for MR reduction is welcome and transcatheter mitral valve interventions provide complementary strategies in the drive for more safe and effective therapies for patients. Surgical repair will be the standard for many years, certainly in low risk DMR. Randomised trials that challenge and enhance our understanding of new technologies are vital, and will guide the risk-benefit analysis of different approaches. This will permit more tailored care according to individual patient profile. Multi-disciplinary and collaborative practice is essential to achieving optimal standard of care.