EDITORIAL COMMENTARY
VT reduction with ablation: A transitive relation to mortality rate? Marc W. Deyell, MD, MSc, FHRS,* Joshua M. Cooper, MD, FHRS† From the *Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, and †Electrophysiology Section, Division of Cardiology, Temple University Health System, Philadelphia, Pennsylvania. The field of catheter ablation of ventricular tachycardia (VT) is growing up fast, having emerged as an effective therapy for the treatment of recurrent VT. Advances in our understanding of scar-based VT in structural heart disease and various cardiomyopathy substrates, along with the concomitant evolution of ablation and imaging technology, have improved the safety and efficacy of this procedure. These advances have led directly to our ability and willingness to address more complex arrhythmia substrates and utilize catheter ablation earlier in the course of VT. It is 2015 and we have demonstrated that we can tackle recurrent VT in the electrophysiology laboratory with reductions in arrhythmia burden and implantable cardioverter-defibrillator therapies. But in the current health care environment, it is not sufficient to simply show the electrophysiological efficacy of a treatment (ie, reduction in arrhythmia burden). To further advance the care of patients with VT, we must also demonstrate the impact of catheter ablation on more compelling outcomes such as quality of life, health care utilization, heart failure, and mortality. There is no question that the population with VT is not an easy group to study. Measuring the impact of catheter ablation on hard outcomes requires the coordination of research efforts beyond the single-center experience that has dominated the VT ablation literature to date. The multicenter collaborative study by Tung et al1 in this issue of HeartRhythm represents another significant advance toward this goal.
Reexamining outcome measures for VT ablation The onset of VT in patients with structural heart disease portends an adverse prognosis, not only for overall mortality but also for heart failure hospitalization.2 It is equally clear that VT is modifiable. What is not clear, however, is whether therapy for VT can alter outcomes beyond reductions in
Dr Cooper serves as a consultant to Biosense Webster. Address reprint requests and correspondence: Dr Marc W. Deyell, Heart Rhythm Services, St. Paul’s Hospital, 211 – 1033 Davie St, Vancouver, BC, Canada V6E 1M7. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
VT recurrence and implantable cardioverter-defibrillator therapy. In the general cardiology community, healthy skepticism remains as to whether we can truly modify the clinical course of patients with recurrent VT. A common notion is that treatment of VT, while effective, may simply convert patients from an arrhythmic to a nonarrhythmic mode of death, without affecting overall prognosis. This point of view resonates more strongly with those caring for patients with end-stage heart failure. Yet the data from Tung et al1 demonstrate that the mortality difference between patients who were free of VT and those with recurrent VT after ablation persisted across the clinical spectrum of heart failure. In fact, the greatest benefit appeared to be in those with an ejection fraction of o30% and those with advanced heart failure class. This observation is at odds with the “conversion” hypothesis that we are merely changing the mechanism of death without having an impact on mortality.
Association vs causation Observational studies, even large multicenter collaborations such as the present article1 and others,3 cannot demonstrate that catheter ablation (whether as primary therapy or after antiarrhythmic drug failure) is the beneficial agent in patients with recurrent VT. An observed mortality benefit after successful ablation may simply be related to the fact that patients with favorable ablation results are those who already had a better underlying prognosis. Certainly, many of the risk factors for VT ablation failure also herald worse clinical outcomes. The apparent salutary benefit of VT ablation could thus be a consequence of selecting patients with a better medical forecast even if an ablation had not been performed. This hypothesis is hard to refute in the absence of a randomized trial. Curiously, the association between arrhythmia burden reduction and clinical outcomes has not been consistently observed with respect to atrial fibrillation treatment in heart failure patients with structural heart disease. The development of atrial fibrillation in patients with congestive heart failure is also associated with an adverse prognosis.4,5
http://dx.doi.org/10.1016/j.hrthm.2015.07.009
Deyell and Cooper
Editorial Commentary
However, the proportion of time spent in sinus rhythm was not associated with an improvement in heart failure status, cardiovascular death, and overall mortality in the antiarrhythmic arm of the Atrial Fibrillation and Congestive Heart Failure trial.6 This discrepancy gives circumstantial support to the notion that reducing VT burden may have therapeutic benefit. Therefore, despite the limitations of the observational data from Tung et al,1 the apparent mortality improvement after successful VT ablation should not be easily discounted.
Tertiary care center data While this multicenter observational study by Tung et al1 is an important stepping stone, it does not answer the question of whether routine VT ablation improves mortality or other health outcomes. Limitations to the available data, patient selection biases, and cause-and-effect uncertainties restrict firm conclusions. The reported VT ablation procedures span over a decade (2002–2013), during which time there have been major changes in technology and techniques, making this a heterogeneous intervention even beyond individual operator practices. The median follow-up of 1.4 years limits us from seeing a longer-term effect. As with all nonrandomized studies, patients were rejected vs selected for VT ablation based on the judgment of the operator; thus, procedural outcome data may be biased in favor of a better clinical result. In contrast, the tertiary referral nature of this population may select for more complex patients, negatively biasing the data. The 70% observed freedom from VT within 1 year in this study must be considered specific to this unique population of referred patients who were in the hands of expert clinicians. As with any procedure, clinical outcomes are critically dependent on appropriate patient selection, proficiency of the operator, perioperative clinical judgment, and management of the patients. The reported results of this study therefore cannot be extrapolated to a spectrum of centers with varying expertise and patient populations.
The road ahead One clear take-home message from this study is the increased mortality associated with recurrent VT, which is more dramatic in patients with an ejection fraction of o30% and more advanced heart failure. This observation should
2009 further galvanize the cardiology community to improve outcomes in this population. In mathematics, a transitive relation tells us that A ¼ C when A ¼ B and B ¼ C, but the biological complexities we manage in medicine cannot be reduced to this same simple principle. While VT ablation may reduce the future incidence of VT, and VT recurrence is associated with an increase in mortality, one cannot directly conclude that VT ablation will reduce mortality without randomized trials designed to address this specific relationship. The forthcoming results of the Ventricular Tachycardia Ablation vs Enhanced Drug Therapy in Structural Heart Disease trial in 2016 will be the first in a series of randomized trials powered to evaluate the impact of catheter ablation on hard outcomes in patients with recurrent VT. The increasing emergence of multicenter collaborative studies of catheter ablation for VT shows the incredible promise of the academic electrophysiology community to tackle this difficult patient population. With rapid advances in ablation technology and new pathophysiological insights, we are growing up fast and are up for the challenge.
References 1. Tung R, Vaseghi M, Frankel DS, et al. Freedom from recurrent ventricular tachycardia after catheter ablation is associated with improved survival in patients with structural heart disease: An International VT Ablation Center Collaborative Group study. Heart Rhythm 2015;12:1997–2007. 2. Moss AJ, Greenberg H, Case RB, Zareba W, Hall WJ, Brown MW, Daubert JP, McNitt S, Andrews ML, Elkin AD; Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II) Research Group. Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator. Circulation 2004;110:3760–3765. 3. Stevenson WG, Wilber DJ, Natale A, et al; Multicenter Thermocool VT Ablation Trial Investigators. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the Multicenter Thermocool Ventricular Tachycardia Ablation trial. Circulation 2008;118:2773–2782. 4. Ford I, Robertson M, Komajda M, Böhm M, Borer JS, Tavazzi L, Swedberg K. Top ten risk factors for morbidity and mortality in patients with chronic systolic heart failure and elevated heart rate: the SHIFT Risk Model. Int J Cardiol 2015;184:163–169. 5. Mentz RJ, Chung MJ, Gheorghiade M, Pang PS, Kwasny MJ, Ambrosy AP, Vaduganathan M, O’Connor CM, Swedberg K, Zannad F, Konstam MA, Maggioni AP. Atrial fibrillation or flutter on initial electrocardiogram is associated with worse outcomes in patients admitted for worsening heart failure with reduced ejection fraction: findings from the EVEREST Trial. Am Heart J 2012;164: 884–892.e2. 6. Talajic M, Khairy P, Levesque S, et al; AF-CHF Investigators. Maintenance of sinus rhythm and survival in patients with heart failure and atrial fibrillation. J Am Coll Cardiol 2010;55:1796–1802.
VT reduction with ablation: A transitive relation to mortality rate? Marc W. Deyell, MD, MSc, FHRS,* Joshua M. Cooper, MD, FHRS† From the *Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, and †Electrophysiology Section, Division of Cardiology, Temple University Health System, Philadelphia, Pennsylvania. The field of catheter ablation of ventricular tachycardia (VT) is growing up fast, having emerged as an effective therapy for the treatment of recurrent VT. Advances in our understanding of scar-based VT in structural heart disease and various cardiomyopathy substrates, along with the concomitant evolution of ablation and imaging technology, have improved the safety and efficacy of this procedure. These advances have led directly to our ability and willingness to address more complex arrhythmia substrates and utilize catheter ablation earlier in the course of VT. It is 2015 and we have demonstrated that we can tackle recurrent VT in the electrophysiology laboratory with reductions in arrhythmia burden and implantable cardioverter-defibrillator therapies. But in the current health care environment, it is not sufficient to simply show the electrophysiological efficacy of a treatment (ie, reduction in arrhythmia burden). To further advance the care of patients with VT, we must also demonstrate the impact of catheter ablation on more compelling outcomes such as quality of life, health care utilization, heart failure, and mortality. There is no question that the population with VT is not an easy group to study. Measuring the impact of catheter ablation on hard outcomes requires the coordination of research efforts beyond the single-center experience that has dominated the VT ablation literature to date. The multicenter collaborative study by Tung et al1 in this issue of HeartRhythm represents another significant advance toward this goal.
Reexamining outcome measures for VT ablation The onset of VT in patients with structural heart disease portends an adverse prognosis, not only for overall mortality but also for heart failure hospitalization.2 It is equally clear that VT is modifiable. What is not clear, however, is whether therapy for VT can alter outcomes beyond reductions in
Dr Cooper serves as a consultant to Biosense Webster. Address reprint requests and correspondence: Dr Marc W. Deyell, Heart Rhythm Services, St. Paul’s Hospital, 211 – 1033 Davie St, Vancouver, BC, Canada V6E 1M7. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
VT recurrence and implantable cardioverter-defibrillator therapy. In the general cardiology community, healthy skepticism remains as to whether we can truly modify the clinical course of patients with recurrent VT. A common notion is that treatment of VT, while effective, may simply convert patients from an arrhythmic to a nonarrhythmic mode of death, without affecting overall prognosis. This point of view resonates more strongly with those caring for patients with end-stage heart failure. Yet the data from Tung et al1 demonstrate that the mortality difference between patients who were free of VT and those with recurrent VT after ablation persisted across the clinical spectrum of heart failure. In fact, the greatest benefit appeared to be in those with an ejection fraction of o30% and those with advanced heart failure class. This observation is at odds with the “conversion” hypothesis that we are merely changing the mechanism of death without having an impact on mortality.
Association vs causation Observational studies, even large multicenter collaborations such as the present article1 and others,3 cannot demonstrate that catheter ablation (whether as primary therapy or after antiarrhythmic drug failure) is the beneficial agent in patients with recurrent VT. An observed mortality benefit after successful ablation may simply be related to the fact that patients with favorable ablation results are those who already had a better underlying prognosis. Certainly, many of the risk factors for VT ablation failure also herald worse clinical outcomes. The apparent salutary benefit of VT ablation could thus be a consequence of selecting patients with a better medical forecast even if an ablation had not been performed. This hypothesis is hard to refute in the absence of a randomized trial. Curiously, the association between arrhythmia burden reduction and clinical outcomes has not been consistently observed with respect to atrial fibrillation treatment in heart failure patients with structural heart disease. The development of atrial fibrillation in patients with congestive heart failure is also associated with an adverse prognosis.4,5
http://dx.doi.org/10.1016/j.hrthm.2015.07.009
Deyell and Cooper
Editorial Commentary
However, the proportion of time spent in sinus rhythm was not associated with an improvement in heart failure status, cardiovascular death, and overall mortality in the antiarrhythmic arm of the Atrial Fibrillation and Congestive Heart Failure trial.6 This discrepancy gives circumstantial support to the notion that reducing VT burden may have therapeutic benefit. Therefore, despite the limitations of the observational data from Tung et al,1 the apparent mortality improvement after successful VT ablation should not be easily discounted.
Tertiary care center data While this multicenter observational study by Tung et al1 is an important stepping stone, it does not answer the question of whether routine VT ablation improves mortality or other health outcomes. Limitations to the available data, patient selection biases, and cause-and-effect uncertainties restrict firm conclusions. The reported VT ablation procedures span over a decade (2002–2013), during which time there have been major changes in technology and techniques, making this a heterogeneous intervention even beyond individual operator practices. The median follow-up of 1.4 years limits us from seeing a longer-term effect. As with all nonrandomized studies, patients were rejected vs selected for VT ablation based on the judgment of the operator; thus, procedural outcome data may be biased in favor of a better clinical result. In contrast, the tertiary referral nature of this population may select for more complex patients, negatively biasing the data. The 70% observed freedom from VT within 1 year in this study must be considered specific to this unique population of referred patients who were in the hands of expert clinicians. As with any procedure, clinical outcomes are critically dependent on appropriate patient selection, proficiency of the operator, perioperative clinical judgment, and management of the patients. The reported results of this study therefore cannot be extrapolated to a spectrum of centers with varying expertise and patient populations.
The road ahead One clear take-home message from this study is the increased mortality associated with recurrent VT, which is more dramatic in patients with an ejection fraction of o30% and more advanced heart failure. This observation should
2009 further galvanize the cardiology community to improve outcomes in this population. In mathematics, a transitive relation tells us that A ¼ C when A ¼ B and B ¼ C, but the biological complexities we manage in medicine cannot be reduced to this same simple principle. While VT ablation may reduce the future incidence of VT, and VT recurrence is associated with an increase in mortality, one cannot directly conclude that VT ablation will reduce mortality without randomized trials designed to address this specific relationship. The forthcoming results of the Ventricular Tachycardia Ablation vs Enhanced Drug Therapy in Structural Heart Disease trial in 2016 will be the first in a series of randomized trials powered to evaluate the impact of catheter ablation on hard outcomes in patients with recurrent VT. The increasing emergence of multicenter collaborative studies of catheter ablation for VT shows the incredible promise of the academic electrophysiology community to tackle this difficult patient population. With rapid advances in ablation technology and new pathophysiological insights, we are growing up fast and are up for the challenge.
References 1. Tung R, Vaseghi M, Frankel DS, et al. Freedom from recurrent ventricular tachycardia after catheter ablation is associated with improved survival in patients with structural heart disease: An International VT Ablation Center Collaborative Group study. Heart Rhythm 2015;12:1997–2007. 2. Moss AJ, Greenberg H, Case RB, Zareba W, Hall WJ, Brown MW, Daubert JP, McNitt S, Andrews ML, Elkin AD; Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II) Research Group. Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator. Circulation 2004;110:3760–3765. 3. Stevenson WG, Wilber DJ, Natale A, et al; Multicenter Thermocool VT Ablation Trial Investigators. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the Multicenter Thermocool Ventricular Tachycardia Ablation trial. Circulation 2008;118:2773–2782. 4. Ford I, Robertson M, Komajda M, Böhm M, Borer JS, Tavazzi L, Swedberg K. Top ten risk factors for morbidity and mortality in patients with chronic systolic heart failure and elevated heart rate: the SHIFT Risk Model. Int J Cardiol 2015;184:163–169. 5. Mentz RJ, Chung MJ, Gheorghiade M, Pang PS, Kwasny MJ, Ambrosy AP, Vaduganathan M, O’Connor CM, Swedberg K, Zannad F, Konstam MA, Maggioni AP. Atrial fibrillation or flutter on initial electrocardiogram is associated with worse outcomes in patients admitted for worsening heart failure with reduced ejection fraction: findings from the EVEREST Trial. Am Heart J 2012;164: 884–892.e2. 6. Talajic M, Khairy P, Levesque S, et al; AF-CHF Investigators. Maintenance of sinus rhythm and survival in patients with heart failure and atrial fibrillation. J Am Coll Cardiol 2010;55:1796–1802.
