How innovation can unleash tremendous growth in the $3.4 billion AF ablation market

Shlomo Ben-Haim (London, UK), a professor of medicine and serial entrepreneur in the medical device industry, examines the drivers of expansion of the atrial fibrillation (AF) ablation market, the existent barriers to market penetration and explains how efficiency and efficacy of catheter ablation need to be enhanced in order to unlock its true growth potential.  

The $3.4 billion atrial fibrillation (AF) ablation market has been ripe for break-out growth for many years. AF ablation has many favourable characteristics—a large and expanding patient population, heightened awareness of AF-related morbidity and associated costs, and acceptance of interventional treatment, to name just a few. Despite these positive fundamentals, AF ablation market growth has been somewhat constrained. In 2007 following medical societies’ release of an expert consensus document on catheter ablation, there were expectations for AF ablation revenue growth of more than 20%. The four major catheter ablation manufacturers invested in novel technology, primarily through acquisitions at an aggregate value of approximately $735 million,¹ to increase their participation in this high-growth, high margin segment. However, excluding contribution from acquired companies, AF sales expansion has hovered around 10% for manufacturers for the past couple of years.²

Drivers of AF ablation abound

1. Rising prevalence and incidence: AF affects an estimated 33.5 million people worldwide,³ and the patient population is expected to increase substantially over the next several decades based on demographics alone, as the prevalence of AF becomes more pronounced in individuals between the ages of 65 and 80.⁴ In addition, recent research has shown that the incidence of AF is rising,⁵ reflecting the greater incidence of comorbid conditions, such as hypertension, obesity, and sleep apnoea, among others. In just the United States, AF is expected to affect 15.9 million people by 2050.⁶
   
2. Increased diagnoses: Heightened surveillance is another driver of higher reported AF incidence.⁵ Multiple stakeholders—medical societies, government bodies, and large non-profit associations—have devoted significant resources to physician education and patient awareness. While these efforts have largely been focused on reduction of ischaemic stroke (a costly consequence of AF), diagnoses are increasing and expanding the pool of catheter ablation candidates.
3. Catheter ablation has reached the “big time”: In addition, catheter ablation has moved from expert consensus statements to inclusion in formal medical guidelines, as clinical data have demonstrated catheter ablation to be superior to antiarrhythymic drugs at maintaining normal sinus rhythm.⁷ Catheter ablation now has a Class IA recommendation, a clear endorsement of the treatment, for patients with paroxysmal AF who are intolerant of an antiarrhytmic drug. Catheter ablation may be considered a first-line therapy in some patients. Guidelines have also embraced the concept of shared decision-making, elevating the patient’s wishes in the treatment decision.^8,9
   
4. Empowered patients: Patients, themselves, are another driver of catheter ablation growth. AF has a significant negative impact on quality of life (QoL) for many patients. As the side effects of antiarrhythmic drugs can also negatively affect QoL, many patients are interested in an intervention that will provide freedom from AF. Patients and caregivers are becoming increasingly proactive with regard to treatment options and are no longer relying solely on physicians. In the United States, over 60% of individuals with Internet access have searched online for information about a medical condition.¹⁰ WebMD and patient-oriented sites, such as PatientsLikeMe.com, have extensive reach and are creating more engaged, knowledgeable healthcare “consumers”. In addition, there are numerous patient advocacy groups and online discussion forums dedicated to AF. Of note, electrophysiology (EP) medical societies from all geographic regions recently released a position paper that addresses patient empowerment in decision making and highlighted some of these patient advocacy groups and forums.¹¹

Barriers to market penetration

Only about 1% of AF patients receive interventional treatment.¹² Underpenetration of the catheter ablation market reflects clinical inertia, supply constraints (efficiency), and treatment durability (efficacy).

1. Clinical inertia: Clinical inertia can manifest in several ways. One example is the time lag between endorsement by medical societies and adoption in clinical practice. Clinical inertia can delay timely referral of appropriate patients for catheter ablation. However, more engaged patients could change this dynamic, as knowledgeable patients introduce catheter ablation into the treatment discussion with general providers and cardiologists.
2. Efficiency: Catheter ablation penetration is somewhat constrained by the number of EP labs. There are an estimated 6,000 EP labs worldwide. Thus, penetration reflects the number of catheter ablations that can be performed daily at these labs. Procedure times vary based on several factors, including type of AF treated (paroxysmal vs. persistent), techniques and technologies used, and operator experience. The procedure time for the least complex case—paroxysmal AF treated by pulmonary vein isolation—averages nearly three hours,¹³ limiting the number of cases that can be performed each day. More complex ablation techniques can take much longer to perform. To meaningfully increase penetration of the catheter ablation market, greater procedural efficiency is needed.
3. Efficacy: Treatment durability is another factor constraining penetration of the catheter ablation market. While many patients continue to be free from AF one year after catheter ablation, most patients experience AF recurrence over time. At just two years after catheter ablation, a recent meta-analysis showed that nearly half of patients had treatment failure, ie. AF returned.¹⁴ The reason for AF recurrence is often because the initial ablation was not truly transmural, ie. the ablation did not permeate the tissue depth. When ablation lines are not transmural, pulmonary vein reconnection occurs and AF resumes. In one study with median follow up of 4.8 years, the majority of patients (53.6%) had recurrent AF. Of these patients, 94% had evidence of pulmonary vein reconnection. During follow-up, some patients progressed to more severe forms of AF,¹⁵ which is more difficult to treat. Because of pulmonary vein reconnection, an estimated 20%-40% of patients undergo repeat ablations.¹⁶ However, the frequency of repeat procedures is highly variable, with data showing that over 50% of patients require second or third catheter ablations.⁷

The economics of AF

AF imposes an enormous economic burden on healthcare systems, with hospitalisations and emergency room visits representing the highest cost areas. A recent analysis pegged the incremental healthcare costs for AF at $6.0 billion in the USA, as direct medical costs for AF patients can be 73% higher than for patients without AF. However, as AF is associated with many comorbidities, the total incremental healthcare costs for AF patients is estimated to be $26.0 billion in the USA alone.¹⁷

Regarding cost-effectiveness of catheter ablation, both public and private payors have increased their focus on effectiveness and outcomes. Although catheter ablation has a higher upfront cost than medical therapy, several analyses have shown that catheter ablation is cost-effective from a health economics perspective. The length of time for cost parity in these analyses ranges from 3.2 years to 10 years, reflecting differing patient population and cost assumptions.¹⁸ However, the two variables that most affect the time period for cost parity are repeat procedures and long-term treatment durability.

Unlocking AF ablation market growth

Both efficiency and efficacy of catheter ablation need to be enhanced in order to achieve substantial penetration of ablation in the AF market and unlock its true growth potential. New technologies strive to do just that: streamline the procedure and enhance treatment durability. For instance, contact force sensing catheters, which use impedance as a proxy to gauge whether ablation will be transmural, have shown higher-than-average treatment success rates at one year when the “right” amount of pressure (ie. contact force) is applied to heart tissue.¹⁹ It remains to be seen whether freedom from AF rates will remain robust in long-term follow-up. However, these new ablation catheters have not demonstrated improved procedural efficiency, with an average procedure time of 3.7 hours.¹⁹

To increase both procedure efficiency and efficacy, clinicians need a true reading that lesion permanency and transmurality has been achieved. Currently, physicians use clinical judgment, combined with readings from navigation software, to assess how long to apply energy to tissue to create a lesion. Often, clinicians only learn that an ablation line was not transmural when the patient’s AF resumes. Thus, the real-time ability to differentiate between a lesion that provides a temporary versus a permanent block is critical to achieving treatment durability. The corollary of this real-time lesion assessment capability is that safety should be enhanced, as the system would alert the clinician when to stop ablation and thereby prevent “collateral damage” to surrounding tissue.

This type of innovation will also serve to simplify the procedure, which would require less specialised skill and knowledge and enable more cardiologists to perform catheter ablations safely, quickly, and effectively. Such a “turnkey” solution is what is needed to drive a material increase in the percentage of patients who undergo catheter ablation and unlock the tremendous growth inherent to the AF ablation market.

References

1. Press releases from Boston-Scientific, Medtronic, and St Jude Medical
2. SEC filings for Boston-Scientific, Johnson & Johnson, Medtronic, and St Jude Medical
3. Chugh SS, Havmoeller R, Narayannan K, et al. Worldwide epidemiology of atrial fibrillation: A global burden of disease 2010 study. Circulation 2014; 129:837–847
4. Go AS, Hylek EM, Phillips KA, Chang YC, et al. Prevalence of diagnosed atrial fibrillation in adults: National implications for rhythm and stroke prevention: the Anticoagulation and risk factors in atrial fibrillation (ATRIA) study. JAMA 2001; 285:2370–2375
5. Schnabel RB, Gona P, Larson MG, Beiser AS, et al. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 2015; 386:154–62
6. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006; 114:119–25
7. Agency for Healthcare Research and Quality. Technology assessment: Catheter ablation for treatment of atrial fibrillation. 20 April 2015
8. Camm AJ, Lip GY, De Caterina R, Savelieva I, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation–developed with the special contribution of the European Heart Rhythm Association. Europace 2012; 14:1385–413
9. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol 2014; 64:e1–76
10. Centers for Disease Control and Prevention. Use of the internet for health information: United States, 2009
11. Lane DA, Aguinaga L, Blomstrom-Lundqvist C, Boriani G, et al. Cardiac tachyarrhythmias and patient values and preferences for their management: the European Heart Rhythm Association (EHRA) consensus document endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE). Europace 2015; doi:10.1093/europace/euv233.
12. Kim D, Ahn H. Current status and future of cardiac mapping in atrial fibrillation. 2012.
13. Boersma LVA, Castella M, van Boven WJ, Beurreuzo A, et al. Atrial fibrillation catheter ablation versus surgical ablation treatment (FAST): A 2-center randomized clinical trial. Circulation 2012; 125:23–30
14. Ganesan AN, Shipp NJ, Brooks AG, Kulik P, et al. Long-term outcomes of catheter ablation of atrial fibrillation: A systematic review and meta-analysis. J Am Heart Assoc 2013; 2:e0045–49
15. Ouyang F, Tilz R, Chun J, Schmidt B, et al. Long-term results of catheter ablation in paroxysmal atrial fibrillation: Lessons from a 5-year follow-up. Circulation 2010; 122:2368–77
16. Calkins H, Kuck KH, Cappato R, Brugada J, et al. 2012 HRS/EHRA/ECAS Expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace 2012; 14:528–606
17. Kim MH, Johnston SS, Chu BC, Dalal MR, Schulman KL. Estimation of total incremental health care costs in patients with atrial fibrillation in the United States. Circ Cardiovasc Qual Outcomes 2011; 4:313–20
18. Khaykin Y, Shamiss Y. Cost of AF ablation: Where do we stand? Cardiol Res Pract 2011; 2011:589–781
19. Natale A, Reddy VY, Monir G, Wilber DJ, et al. Paroxysmal AF catheter ablation with a contact force sensing catheter: Results of the prospective, multicenter SMART-AF trial. J Am Coll Cardiol 2014; 64:647–56

Shlomo Ben-Haim (London, UK), has held faculty positions at Harvard University and the Technion–Israel Institute of technology as a professor of Medicine, Physiology and Biophysics. He developed the CARTO system as part of Biosense, which he co-founded in the 90’s. He is a serial entrepreneur specialising in the fields of healthcare and biotech. He is also the founder of EP Dynamics.