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Pacing-induced cardiomyopathy: just the tip of the iceberg?

Pacing-induced cardiomyopathy: just the tip of the iceberg? Abstract Open in new tabDownload slide Open in new tabDownload slide This editorial refers to ‘Incidence of heart failure after pacemaker implantation: a nationwide Danish Registry-based follow-up study’†, by B. Tayal et al., on page 3641. Pacing-induced cardiomyopathy (PICM) is most commonly thought of as a drop in left ventricular ejection fraction (LVEF) in the setting of chronic, high burden right ventricular (RV) pacing. It has been reported that ∼20% of patients develop PICM after 3–4 years of RV pacing.1 Traditionally, PICM has been viewed as a form of heart failure with reduced ejection fraction (HFrEF), and most studies reporting the incidence of PICM include impaired LVEF in the diagnostic criteria. However, LVEF criteria can have a dramatic effect on the reported incidence of PICM. For example, in a recent study of 118 patients with high burden RV pacing, the incidence of PICM was compared using three different definitions: (i) LVEF ≤40% if baseline LVEF was ≥50%, or an absolute drop in LVEF ≥5% if baseline was <50%; (ii) LVEF ≤40% if baseline LVEF was ≥50%, or an absolute drop in LVEF ≥10% if baseline was <50%; and (iii) absolute drop in LVEF ≥10%, regardless of baseline.2 During a mean follow-up of 3.4 years, the incidence of PICM was 9.3, 5.9, and 39.0% using definitions (i), (ii), and (iii), respectively. Notably, when using definition (iii) (absolute drop in LVEF ≥10% regardless of baseline), 31 out of 46 patients who met the criteria for PICM still had an EF >50% at follow-up. This suggests that many patients who experience detrimental effects from RV pacing may still have a preserved EF and may not meet traditional criteria for PICM. Other studies have demonstrated similar findings.3 Based on these data, it seems likely that traditional definitions of PICM which focus on impaired LVEF may underestimate the impact of high burden RV pacing by failing to account for heart failure symptoms which occur without LVEF falling below 50%. For some patients, PICM may manifest as a form of heart failure with preserved ejection fraction (HFpEF), and definitions of PICM which focus on reduced EF may represent only the tip of a larger PICM iceberg (Take home figure). Take home figure Open in new tabDownload slide Spectrum of potential manifestations for pacing-induced cardiomyopathy. Take home figure Open in new tabDownload slide Spectrum of potential manifestations for pacing-induced cardiomyopathy. However, relatively little is known about the onset of heart failure symptoms in the setting of RV pacing. The study by Tayal and colleagues in this issue of the European Heart Journal provides much needed data on the incidence and time course with which heart failure symptoms emerge following pacemaker implantation.4 The authors leveraged Danish administrative databases to identify a large cohort of >27 000 patients undergoing pacemaker implantation without known history of heart failure. Patients with pacemakers were age and gender matched (ratio of 1:5, cases to controls) to a cohort without pacemakers and without history of heart failure. Using in- and outpatient diagnosis codes, the incidence of new-onset heart failure was compared between cases following pacemaker implantation and controls using a corresponding index date. The primary endpoint was the incidence of new heart failure diagnosis, with death or myocardial infarction modelled as competing risks. At 2-year follow-up, the incidence of new-onset heart failure was 10.6% in patients with pacemakers and 6.7% in controls. Interestingly, the hazard ratio for new-onset heart failure was highest in the first 30 days after pacemaker implantation (5.98) and decreased to 1.84 between days 30 and 180 and to 1.11 between day 180 and 2 years. Although data on pacing burden were not available, when the authors compared patients with a primary pacemaker indication of sinus node dysfunction with those with an indication of heart block, the risk of new-onset heart failure was ∼25% higher in the setting of heart block, providing some support for the hypothesis that the association between pacemaker implantation and new-onset heart failure is mediated by ventricular pacing. The data presented by Tayal and colleagues are important in demonstrating a significant association between pacemaker implantation and new-onset heart failure symptoms. Importantly, they also demonstrate a much more rapid time course for the development of heart failure following pacemaker implantation than the historical model of PICM where cardiomyopathy may take several years to develop. The current study is consistent with other recent reports which have demonstrated an increased risk of new heart failure diagnoses in the first 6 months following pacemaker implantation for heart block.5 These studies provide support for the idea that the definition of PICM should be broadened to include the onset of heart failure symptoms following pacemaker implantation independent of specific LVEF criteria. The data presented by Tayal and colleagues raise additional important questions. Is right ventricle pacing the culprit which leads to new-onset heart failure or is the need for pacemaker implantation a harbinger of an underlying disease process which would have ultimately resulted in heart failure independent of the pacemaker? Stated in a different way, is the relationship between pacemaker implantation and heart failure an association or causation? Studies have demonstrated a significant detrimental effect on cardiac function which can be measured within hours to days of RV pacing.6 Increased cardiac filling pressures, reduced cardiac output, functional mitral regurgitation, and increased susceptibility to atrial arrhythmias are all plausible mechanisms by which RV pacing may trigger heart failure symptoms relatively acutely and well before a significant drop in LVEF occurs.1 Additional mechanistic studies will be necessary to more clearly define the association between pacemaker implantation and heart failure. Are the heart failure diagnoses which occur soon after pacemaker implantation due to systolic dysfunction (i.e. HFrEF) or are they mostly a form of HFpEF? One of the major limitations of the study by Tayal and colleagues is the lack of data on EF. Serial echocardiograms before and after pacemaker implantation will be very useful in providing mechanistic insight in future studies. What should be done to prevent heart failure following pacemaker implantation? Upfront cardiac resynchronization therapy (CRT) or conduction system pacing (CSP) (i.e. His bundle pacing) have been proposed to prevent PICM.7,8 However, if 10–15% of patients develop new-onset heart failure following pacemaker implantation,4,5 does this justify the additional expense and complexity of CRT or CSP as an upfront strategy in all? Many individuals tolerate high burden RV pacing for many years without any discernible adverse effects.9 It is clear that individual susceptibility to the detrimental effects of RV pacing varies substantially, and much more work is needed to identify which individuals are most likely to develop PICM and then target preventive strategies accordingly. The traditional model of PICM, which focuses on a drop in LVEF in the setting of chronic RV pacing, probably represents only one manifestation of PICM. Many individuals may experience new-onset heart failure symptoms after pacemaker implantation, some very soon after. These individuals should also be regarded as having a form of PICM. The study by Tayal and colleagues provides important data to broaden our understanding of the PICM spectrum and sets the stage for future studies to more clearly define the breadth and depth of the PICM iceberg. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. Footnotes † doi:10.1093/eurheartj/ehz584. References 1 Merchant FM , Mittal S. Pacing-induced cardiomyopathy . Card Electrophysiol Clin 2018 ; 10 : 437 – 445 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Kaye G , Ng JY , Ahmed S , Valencia D , Harrop D , Ng ACT. The prevalence of pacing-induced cardiomyopathy (PICM) in patients with long term right ventricular pacing – is it a matter of definition? Heart Lung Circ 2019 ; 28 : 1027 – 1033 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Yu CM , Fang F , Luo XX , Zhang Q , Azlan H , Razali O. Long-term follow-up results of the pacing to avoid cardiac enlargement (PACE) trial . Eur J Heart Fail 2014 ; 16 : 1016 – 1025 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Tayal B , Fruelund P , Sogaard P , Riahi S , Polcwiartek C , Atwater BD , Gislason G , Risum N , Torp-Pedersen C , Kober L , Kragholm KH. Incidence of heart failure after pacemaker implantation: a nationwide Danish Registry-based follow-up study . Eur Heart J 2019 ; 40 :3641--3648. WorldCat 5 Merchant FM , Hoskins MH , Musat DL , Prillinger JB , Roberts GJ , Nabutovsky Y , Mittal S. Incidence and time course for developing heart failure with high-burden right ventricular pacing . Circ Cardiovasc Qual Outcomes 2017 ; 10 : e003564 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Nahlawi M , Waligora M , Spies SM , Bonow RO , Kadish AH , Goldberger JJ. Left ventricular function during and after right ventricular pacing . J Am Coll Cardiol 2004 ; 44 : 1883 – 1888 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Yu CM , Chan JY , Zhang Q , Omar R , Yip GW , Hussin A , Fang F , Lam KH , Chan HC , Fung JW. Biventricular pacing in patients with bradycardia and normal ejection fraction . N Engl J Med 2009 ; 361 : 2123 – 2134 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Abdelrahman M , Subzposh FA , Beer D , Durr B , Naperkowski A , Sun H , Oren JW , Dandamudi G , Vijayaraman P. Clinical outcomes of His bundle pacing compared to right ventricular pacing . J Am Coll Cardiol 2018 ; 71 : 2319 – 2330 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Ebert M , Jander N , Minners J , Blum T , Doering M , Bollmann A , Hindricks G , Arentz T , Kalusche D , Richter S. Long-term impact of right ventricular pacing on left ventricular systolic function in pacemaker recipients with preserved ejection fraction: results from a large single-center registry . J Am Heart Assoc 2016 ; 5 : e003485 . Google Scholar Crossref Search ADS PubMed WorldCat Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal Oxford University Press

Pacing-induced cardiomyopathy: just the tip of the iceberg?

Merchant, Faisal M
European Heart Journal , Volume 40 (44): 2 – Oct 11, 2019
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References (18)

Publisher
Oxford University Press
Copyright
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.
ISSN
0195-668X
eISSN
1522-9645
DOI
10.1093/eurheartj/ehz715
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Abstract

Abstract Open in new tabDownload slide Open in new tabDownload slide This editorial refers to ‘Incidence of heart failure after pacemaker implantation: a nationwide Danish Registry-based follow-up study’†, by B. Tayal et al., on page 3641. Pacing-induced cardiomyopathy (PICM) is most commonly thought of as a drop in left ventricular ejection fraction (LVEF) in the setting of chronic, high burden right ventricular (RV) pacing. It has been reported that ∼20% of patients develop PICM after 3–4 years of RV pacing.1 Traditionally, PICM has been viewed as a form of heart failure with reduced ejection fraction (HFrEF), and most studies reporting the incidence of PICM include impaired LVEF in the diagnostic criteria. However, LVEF criteria can have a dramatic effect on the reported incidence of PICM. For example, in a recent study of 118 patients with high burden RV pacing, the incidence of PICM was compared using three different definitions: (i) LVEF ≤40% if baseline LVEF was ≥50%, or an absolute drop in LVEF ≥5% if baseline was <50%; (ii) LVEF ≤40% if baseline LVEF was ≥50%, or an absolute drop in LVEF ≥10% if baseline was <50%; and (iii) absolute drop in LVEF ≥10%, regardless of baseline.2 During a mean follow-up of 3.4 years, the incidence of PICM was 9.3, 5.9, and 39.0% using definitions (i), (ii), and (iii), respectively. Notably, when using definition (iii) (absolute drop in LVEF ≥10% regardless of baseline), 31 out of 46 patients who met the criteria for PICM still had an EF >50% at follow-up. This suggests that many patients who experience detrimental effects from RV pacing may still have a preserved EF and may not meet traditional criteria for PICM. Other studies have demonstrated similar findings.3 Based on these data, it seems likely that traditional definitions of PICM which focus on impaired LVEF may underestimate the impact of high burden RV pacing by failing to account for heart failure symptoms which occur without LVEF falling below 50%. For some patients, PICM may manifest as a form of heart failure with preserved ejection fraction (HFpEF), and definitions of PICM which focus on reduced EF may represent only the tip of a larger PICM iceberg (Take home figure). Take home figure Open in new tabDownload slide Spectrum of potential manifestations for pacing-induced cardiomyopathy. Take home figure Open in new tabDownload slide Spectrum of potential manifestations for pacing-induced cardiomyopathy. However, relatively little is known about the onset of heart failure symptoms in the setting of RV pacing. The study by Tayal and colleagues in this issue of the European Heart Journal provides much needed data on the incidence and time course with which heart failure symptoms emerge following pacemaker implantation.4 The authors leveraged Danish administrative databases to identify a large cohort of >27 000 patients undergoing pacemaker implantation without known history of heart failure. Patients with pacemakers were age and gender matched (ratio of 1:5, cases to controls) to a cohort without pacemakers and without history of heart failure. Using in- and outpatient diagnosis codes, the incidence of new-onset heart failure was compared between cases following pacemaker implantation and controls using a corresponding index date. The primary endpoint was the incidence of new heart failure diagnosis, with death or myocardial infarction modelled as competing risks. At 2-year follow-up, the incidence of new-onset heart failure was 10.6% in patients with pacemakers and 6.7% in controls. Interestingly, the hazard ratio for new-onset heart failure was highest in the first 30 days after pacemaker implantation (5.98) and decreased to 1.84 between days 30 and 180 and to 1.11 between day 180 and 2 years. Although data on pacing burden were not available, when the authors compared patients with a primary pacemaker indication of sinus node dysfunction with those with an indication of heart block, the risk of new-onset heart failure was ∼25% higher in the setting of heart block, providing some support for the hypothesis that the association between pacemaker implantation and new-onset heart failure is mediated by ventricular pacing. The data presented by Tayal and colleagues are important in demonstrating a significant association between pacemaker implantation and new-onset heart failure symptoms. Importantly, they also demonstrate a much more rapid time course for the development of heart failure following pacemaker implantation than the historical model of PICM where cardiomyopathy may take several years to develop. The current study is consistent with other recent reports which have demonstrated an increased risk of new heart failure diagnoses in the first 6 months following pacemaker implantation for heart block.5 These studies provide support for the idea that the definition of PICM should be broadened to include the onset of heart failure symptoms following pacemaker implantation independent of specific LVEF criteria. The data presented by Tayal and colleagues raise additional important questions. Is right ventricle pacing the culprit which leads to new-onset heart failure or is the need for pacemaker implantation a harbinger of an underlying disease process which would have ultimately resulted in heart failure independent of the pacemaker? Stated in a different way, is the relationship between pacemaker implantation and heart failure an association or causation? Studies have demonstrated a significant detrimental effect on cardiac function which can be measured within hours to days of RV pacing.6 Increased cardiac filling pressures, reduced cardiac output, functional mitral regurgitation, and increased susceptibility to atrial arrhythmias are all plausible mechanisms by which RV pacing may trigger heart failure symptoms relatively acutely and well before a significant drop in LVEF occurs.1 Additional mechanistic studies will be necessary to more clearly define the association between pacemaker implantation and heart failure. Are the heart failure diagnoses which occur soon after pacemaker implantation due to systolic dysfunction (i.e. HFrEF) or are they mostly a form of HFpEF? One of the major limitations of the study by Tayal and colleagues is the lack of data on EF. Serial echocardiograms before and after pacemaker implantation will be very useful in providing mechanistic insight in future studies. What should be done to prevent heart failure following pacemaker implantation? Upfront cardiac resynchronization therapy (CRT) or conduction system pacing (CSP) (i.e. His bundle pacing) have been proposed to prevent PICM.7,8 However, if 10–15% of patients develop new-onset heart failure following pacemaker implantation,4,5 does this justify the additional expense and complexity of CRT or CSP as an upfront strategy in all? Many individuals tolerate high burden RV pacing for many years without any discernible adverse effects.9 It is clear that individual susceptibility to the detrimental effects of RV pacing varies substantially, and much more work is needed to identify which individuals are most likely to develop PICM and then target preventive strategies accordingly. The traditional model of PICM, which focuses on a drop in LVEF in the setting of chronic RV pacing, probably represents only one manifestation of PICM. Many individuals may experience new-onset heart failure symptoms after pacemaker implantation, some very soon after. These individuals should also be regarded as having a form of PICM. The study by Tayal and colleagues provides important data to broaden our understanding of the PICM spectrum and sets the stage for future studies to more clearly define the breadth and depth of the PICM iceberg. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. Footnotes † doi:10.1093/eurheartj/ehz584. References 1 Merchant FM , Mittal S. Pacing-induced cardiomyopathy . Card Electrophysiol Clin 2018 ; 10 : 437 – 445 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Kaye G , Ng JY , Ahmed S , Valencia D , Harrop D , Ng ACT. The prevalence of pacing-induced cardiomyopathy (PICM) in patients with long term right ventricular pacing – is it a matter of definition? Heart Lung Circ 2019 ; 28 : 1027 – 1033 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Yu CM , Fang F , Luo XX , Zhang Q , Azlan H , Razali O. Long-term follow-up results of the pacing to avoid cardiac enlargement (PACE) trial . Eur J Heart Fail 2014 ; 16 : 1016 – 1025 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Tayal B , Fruelund P , Sogaard P , Riahi S , Polcwiartek C , Atwater BD , Gislason G , Risum N , Torp-Pedersen C , Kober L , Kragholm KH. Incidence of heart failure after pacemaker implantation: a nationwide Danish Registry-based follow-up study . Eur Heart J 2019 ; 40 :3641--3648. WorldCat 5 Merchant FM , Hoskins MH , Musat DL , Prillinger JB , Roberts GJ , Nabutovsky Y , Mittal S. Incidence and time course for developing heart failure with high-burden right ventricular pacing . Circ Cardiovasc Qual Outcomes 2017 ; 10 : e003564 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Nahlawi M , Waligora M , Spies SM , Bonow RO , Kadish AH , Goldberger JJ. Left ventricular function during and after right ventricular pacing . J Am Coll Cardiol 2004 ; 44 : 1883 – 1888 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Yu CM , Chan JY , Zhang Q , Omar R , Yip GW , Hussin A , Fang F , Lam KH , Chan HC , Fung JW. Biventricular pacing in patients with bradycardia and normal ejection fraction . N Engl J Med 2009 ; 361 : 2123 – 2134 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Abdelrahman M , Subzposh FA , Beer D , Durr B , Naperkowski A , Sun H , Oren JW , Dandamudi G , Vijayaraman P. Clinical outcomes of His bundle pacing compared to right ventricular pacing . J Am Coll Cardiol 2018 ; 71 : 2319 – 2330 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Ebert M , Jander N , Minners J , Blum T , Doering M , Bollmann A , Hindricks G , Arentz T , Kalusche D , Richter S. Long-term impact of right ventricular pacing on left ventricular systolic function in pacemaker recipients with preserved ejection fraction: results from a large single-center registry . J Am Heart Assoc 2016 ; 5 : e003485 . Google Scholar Crossref Search ADS PubMed WorldCat Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Journal

European Heart Journal – Oxford University Press

Published: Oct 11, 2019

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