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. 2021 Oct;10(3):154–158. doi: 10.15420/aer.2021.23

The DAPA Trial in the Context of Previous Prophylactic ICD Landmark Trials

Danielle Haanschoten 1, Arif Elvan 1,✉
PMCID: PMC8576491  PMID: 34777819

Abstract

In patients with ischaemic cardiomyopathy and severely reduced left ventricular ejection fraction (LVEF), an arrhythmogenic milieu is created by a complex interplay between myocardial scarring (assessed by cardiac MRI) and multiple other factors (ventricular ectopy, ischaemia and autonomic imbalance), favouring the occurrence of arrhythmic sudden cardiac death (SCD). Currently, a dynamic and robust model of dichotomised SCD risk assessment after primary percutaneous coronary intervention (PCI) is lacking, underlining the urgent need for further refinement of the widely accepted and guidelines-based criteria (ischaemic cardiomyopathy, LVEF ≤35%) for primary prevention. This review addresses the potential additional value of the recently published Defibrillator After Primary Angioplasty (DAPA) trial results. The DAPA trial conveys important messages and provides novel perspectives regarding left ventricular function post-primary PCI as an (early) risk marker for SCD and the impact of prophylactic ICD implantation on survival in this cohort. In the context of other previous primary prevention trials, DAPA was the first trial including only ST-elevation MI patients all treated with acute PCI.

Keywords: ICD therapy, MI, ventricular arrhythmia

Philippe Coumel, one of the founding fathers of modern arrhythmology, stated in 1978: “There are always three main ingredients required for the emergence of a clinical arrhythmia: an arrhythmogenic substrate, a trigger and modulating factors such as imbalanced autonomic nervous tone and electrolyte disorders.”

The basic understanding of the mechanisms underlying ventricular arrhythmia (VA) is essentially unchanged. It is generally accepted that the occurrence of VA in ischaemic cardiomyopathy is an interplay between the presence of fibrotic scar tissue and transient electrical instability creating an arrhythmogenic milieu. An electrical unstable environment may be caused by an ischaemic event, autonomic imbalance, electrolyte disturbances, increased wall stress in heart failure patients or a combination of factors.[1] The potentially lethal combination of these sudden cardiac death (SCD) risk factors is often unique to the individual and may change over time. The latter explains why there are still no optimal risk models available to identify patients with an increased risk of SCD. After all, one SCD that could have been prevented is one too many.

Results of intensive research in the past 20 years have led to an increase in ICD implantations worldwide, of which primary prevention is the most common indication today. In general, the rationale behind secondary prevention ICD implantation is clear and there is no discussion regarding the indication for ICD eligibility in SCD survivors or patients with previous sustained VA. However, selecting patients for primary prevention ICD implantation is a far more complex matter and requires a meticulous decision-making process, with individual risk assessment and counselling. The risks and benefits of ICD implantation need to be discussed based on medical considerations and patients’ personal preferences. Current guidelines recommend implantation of a prophylactic ICD in patients with functional New York Heart Association class I or II–III and left ventricular ejection fraction (LVEF) ≤30–35% at least 40 days post-MI and in US guidelines a condition of 90 days post-revascularisation.[2,3] Real world registry data show that only a minority of patients selected for primary prevention ICD implantation based on current guidelines benefit from the ICD because of a low incidence of appropriate ICD therapy.[4] An Israeli registry documented only 2.6% appropriate ICD therapy in patients with a prophylactic ICD (>70.0% ischaemic cardiomyopathy) after 2.5 years of follow-up.[5] Furthermore, device and lead-related complications and inappropriate ICD shocks are important disadvantages of ICDs, which can have a significant negative impact on patients’ quality of life.[6,7]

In this review, we highlight the gaps of knowledge in the available literature on primary prevention ICDs and the additional value of the Defibrillator After Primary Angioplasty (DAPA) trial results.[8] We also discuss the potential role of contemporary advanced imaging modalities in risk stratification of patients for prophylactic ICD implantation.

Primary Prevention ICD, Ageing Literature?

One of the most important cornerstones of today’s primary prevention ICD implantation guidelines for ischaemic cardiomyopathy is based on the results of MADIT II in 2002.[9] Patients were included based on a history of remote MI (mean 6.7 years after index MI) and LVEF (<30%). Patients who underwent revascularisation within 3 months were excluded from the analysis. This complicates translation of MADIT II to today’s practice, as it is unknown whether outcomes are similar in ST-elevation MI (STEMI) patients who are treated with primary PCI. The MADIT II population was a heterogeneous population from the perspective of Coumel’s triangle of factors involved in arrhythmic SCD. It is unknown whether two hypothetical post-MI patients with comparable LVEF <30% and either: a relatively small myocardial scar and suboptimal revascularised multivessel coronary disease or large MI after a successful revascularisation of a single vessel coronary artery disease, bear the same risks for VA/SCD.

Of note, there is increasing evidence that infarct-related chronic total occlusions may contribute to an enhanced susceptibility for VA in both primary and secondary prevention.[10] Moreover, new advances in late gadolinium enhancement (LGE) cardiac magnetic imaging (CMR) allows a detailed scar characterisation and has potentially promising value in the refinement of risk stratification and prediction of VA/SCD.[11,12] The shortcomings of LVEF as a sole risk stratification factor for post-MI primary ICD indication are clear and it has been criticised numerous times, yet alternatives are still lacking.[13–15]

A recent retrospective cohort analysis of four MADIT studies addressed the most important question in qualification of primary prevention ICD benefit: risk of life-threatening VA against competing risk of non-arrhythmic mortality as a result of pump failure.[16] Patients with the greatest ICD benefit were considered to have an increased 3-year predicted risk of VA and a relatively low predicted 3-year risk for non-arrhythmic mortality, leading to a 74-days life gain in 3 years. A high VA score included established factors such as younger age, prior non-sustained ventricular tachycardia, faster baseline heart rate (increased sympathetic activity) and prior MI. While these factors may contribute to an improved risk stratification scheme, primary prevention trials (MUSTT, SCD-HeFT) using a variability of these criteria, had limited impact on the guidelines.[17,18] The mixture of inclusion criteria, different primary outcomes (all-cause mortality or arrhythmic mortality) and patient populations (including non-ischaemic cardiomyopathy) potentially made interpretation of the available data even more complicated.[19]

Furthermore, preventive measures to reduce the burden of coronary artery disease and heart failure have significantly improved over the past decades and their impact on the incidence of VA/SCD is not fully delineated yet. In conclusion, existing data in the area of primary ICD implantation seem to be outdated and are becoming more and more estranged from contemporary cardiology practice.[20] However, repeating the previous clinical landmark trials, randomising patients with LVEF <30% to ICD implantation compared with optimal medical therapy, would now create an ethical dilemma. Despite promising results of novel heart failure drugs (for example, angiotensin receptor-neprilysin inhibitors), withholding an ICD from patients with LVEF <30% would be difficult to defend, especially in younger patients.[21] Currently, researchers are challenged to develop novel risk stratification models based on observational and retrospective data in patients with severely reduced LVEF.[22]

DAPA Trial and the Timing of Implantation

The latest randomised trial that compared ICD implantation with optimal medical therapy only in patients with LVEF <30% was the DAPA trial.[8] This randomised, multicentre, controlled trial was conducted in high-risk primary PCI patients, defined as either:

  • LVEF <30% (being the only criterion in 66.5% of the participants);

  • failure or suboptimal result of acute revascularisation (TIMI flow less than three in 20.3% of the participants); or

  • a combination of factors, including primary VF and Killip class greater than −2.

The primary endpoint was all-cause mortality after 3 years. Additional survival assessment was performed in February 2019 for the primary endpoint. The trial prematurely ended after inclusion of 266 patients as a result of a slow inclusion rate (38% of the calculated sample size) with 131 patients randomised to the ICD arm and 135 patients to the control arm. The greatest differences from former trials is that every patient underwent primary PCI (according to current standard of care) and echocardiographic LVEF evaluation was performed within 4 days of STEMI, in contrast to persistent low LVEF after remote MI such as in MADIT II, in which ICD implantation was performed approximately 6.7 years after index MI.

Although not confirmed by CMR-LGE imaging, low LVEF early after primary PCI in the DAPA trial may be regarded as a surrogate for a large scar caused by the acute MI (mainly anterior infarctions). Another important difference is that ICD implantation in the DAPA trial was postponed to at least 30 days post-MI (median of 50 days) to overcome the issue of mortality related to heart failure in the early healing phase, as this was the pitfall that caused the negative outcomes of IRIS and DINAMIT.[23,24] Several issues related to the DAPA trial, of which premature termination is the most important factor, limit the ability to draw strong conclusions as justly expressed by Parkash et al.[25] However, some interesting findings need to be recognised and may be used as a guide for future research.

DAPA data show a beneficial impact of early ICD implantation on all-cause mortality within the first 3 years after MI and this was sustained at 9 years of follow-up. In both groups, patients had similar follow-up visits. As such, we consider the potential bias of an improved heart failure treatment regime in the ICD group unlikely. It is reassuring that ICD implantation in low LVEF post-STEMI patients is associated with improved survival in this particular cohort of patients with STEMI treated with primary PCI, which is in line with the results of MADIT II. Nevertheless, it is important to realise that MADIT II focused on ICD benefit in patients with long-term low LVEF in general, while the scope of the DAPA trial is limited to patients in the current era with the widespread use of primary PCI. Different scopes of previous and future ICD trials are shown in Figure 1.

Figure 1: DAPA Trial in the Context of Previous Prophylactic ICD Trials.

Figure 1:

CMR = cardiac MRI; LGE = late gadolinium enhancement; LV = left ventricular; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention.

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A subanalysis of MADIT II revealed that in patients with recent revascularisation (less than 6 months previously), there was no benefit of ICD implantation.[26] In contrast, the DAPA trial shows that appropriate ICD therapy occurred in five patients (1.9%) within the first 8 months after implantation. Primary PCI of the infarct-related artery reduces mortality by reducing infarct size and diminishing myocardial scarring-related arrhythmogenicity.[27] However, several questions remain unanswered: Is arrhythmic SCD in the early healing phase after MI caused by a complex interaction between autonomic imbalance, triggering factors and scar inhomogeneity? Or does the extent of scar burden become more relevant over time after the early remodelling phase?

The following factors are important contributors to VA/SCD risk in the early phase after MI: success of revascularisation, severity of LV dysfunction, electrical instability and wall stress. Although we know the common denominator in the DAPA trial was a large infarction with severe LV dysfunction in the early phase after STEMI, the subgroup of patients with VA was too small to identify true triggers for VA. Another interesting finding of the DAPA trial is that follow-up data suggest the benefit of ICD may extend to patients whose LVEF had improved over time. LVEF increased ≥10.0% in 46.5% of the patients during follow-up. In a subgroup analysis of all patients with LVEF ≥35% (n=117) after 18 months of follow-up, there was a trend towards ICD benefit (HR 0.34; 95% CI [0.09–1.25]; p=0.100). Although these analyses are exploratory, similar results were found in a subanalysis of the SCD-HeFT.[28] Furthermore, the VALIANT trial has shown that baseline LVEF <40% was strongly associated with the occurrence of SCD in hospital and after discharge and explained a limited amount of SCD risk during long-term follow-up (longer than 6 months).[29]

To conclude, the DAPA trial has several limitations and lacks potentially important data regarding coronary revascularisation during follow-up and novel medical treatment strategies. Nevertheless, it is unique in its design compared with other primary prevention trials as patients all underwent primary PCI, an essential part of today’s treatment strategy in acute MI patients. Pharmacological and cardiac resynchronisation trials have shown that neurohormonal antagonists (for example angiotensin receptor–neprilysin inhibitors) and cardiac resynchronisation therapy (CRT) have a significant impact on heart failure hospitalisation and heart failure related death, but the effect on SCD is not well appreciated.[30] As the journey of advancements in ICD therapy for primary prevention will continue, there is a clear need for future trials focusing on SCD risk assessment based on advanced substrate characterisation combined with contemporary coronary revascularisation and pharmacological therapy.

The Value of Cardiac MRI

Although scar characterisation with LGE-CMR imaging is gaining interest, it still has several limitations. Solid data regarding the added value of substrate imaging for a more tailored and robust risk stratification of SCD in reduced LVEF patients are lacking.[31] The occurrence of VA/SCD does not solely depend on the size or other characteristics of the substrate. The susceptibility for VA/SCD is based on a complex interplay of multiple factors.[32,33] Furthermore, there is currently no consensus on which CMR method should be used to identify patients at risk for VA.[34,35] Various observational studies indicated that the peri-infarct zone assessed by CMR is a strong predictor of all-cause mortality and arrhythmic outcomes in ischaemic cardiomyopathy in both severely depressed and moderately depressed LV function and even CRT patients.[33,36] However, there is significant heterogeneity between studies regarding type and dose of contrast agent administration, CMR sequence and assessment of border zones.[37,38]

Also, timing of CMR after MI was not reported in most studies. As such, data regarding the importance of temporal dynamics of scar aging on VA risk are limited.[35,39] The reason why young patients may benefit most from ICD may be the result of fewer competing risks of death.[40] However, the impact of the dynamic nature of the scar healing process irrespective of patient age is not fully delineated yet.[41,42] First presentation of VA/SCD may occur 10 years after the index MI, which younger patients are more likely to experience. Whether this is caused by a triggering factor (for example, acute ischaemia in progressed coronary disease), heart failure or a chronic myocardial scar, is unknown.

Future research with CMR imaging at different time points after MI might provide more insights into the dynamic changes in the myocardial substrate. It was recently shown that the absence of conduction channels in the scar tissue and limited scar mass (<10 g) can identify patients at a very low risk of VAs in a primary prevention population with a negative predictive value of 97.2%.[43] Implementation of advanced imaging in the standard follow-up of these patients may allow discrimination of low risk groups as a first step in refining primary prevention ICD indications, or perhaps even broaden ICD indications in patients with LVEF >35% and LGE presence, a population currently investigated in the CMR GUIDE trial.[44]

Risk Stratification Beyond Left Ventricular Ejection Fraction and Substrate

The results of the PRESERVE EF trial indicate that non-invasive risk factors,for example premature ventricular complexes, increased T wave alternans, reduced heart rate variability, etc., are important warning signals for the risk of VA in post-MI patients, even in preserved LVEF. The results also underline that programmed ventricular stimulation (PVS) may be useful to identify patients at risk for VA in selected cases, as was previously shown in randomised trials, for example MUSTT and MADIT.[45–48] However, patients in the early post-MI period were largely excluded from the above mentioned randomised controlled trials. The PROTECT ICD trial, an international, multicentre randomised controlled trial uses a PVS protocol to discriminate patients with LVEF <40%, early post-MI who will potentially benefit most from an ICD.[49] The combination of CMR imaging and PVS in early post-MI patients (2–40 days), has the potential to fill an important knowledge gap in the landscape of primary prevention ICD implantation indication.

Conclusion

Robust and sophisticated SCD risk stratification in ischaemic cardiomyopathy patients in general, and STEMI patients treated with primary PCI in particular, remains a demanding challenge, as a combination of dynamic factors (e.g. heart failure, coronary revascularisation status and myocardial substrate characteristics) are involved in the susceptibility to SCD. Current guidelines need more nuance based on altered SCD risk levels as a result of contemporary pharmacological and nonpharmacological treatment strategies. The DAPA trial results suggest that the extent of LV dysfunction shortly after STEMI that is treated with primary PCI can be used to identify patients at enhanced risk for early mortality. However, similarly to other characteristics, the ability to predict clinical events may be substantially less after a certain critical time window. Advanced substrate imaging with LGE-CMR has the potential to embrace an important factor that may guide clinicians in providing tailored therapies to decrease disease burden and increase survival, but we are not there yet. With respect to previous landmark primary prevention trials, needed with the inclusion of a contemporary population, treated with updated randomised trials (including invasive and non-invasive tests) are novel treatment strategies.

Clinical Perspective

  • Current guidelines for primary prevention ICD eligibility are mainly based on left ventricular ejection fraction (LVEF) .30.35%.

  • The shortcomings of LVEF as a sole risk stratification factor for post-MI primary ICD indication are clear, yet alternatives are lacking.

  • Despite limited power, the DAPA trial conveys important messages and provides novel perspectives regarding left ventricular function post-primary percutaneous coronary intervention as an early risk marker for sudden cardiac death.

  • New randomised trials are needed that include a contemporary population, treated with novel treatment strategies.

References

  • 1.Goldberger JJ, Buxton AE, Cain M et al. Risk stratification for arrhythmic sudden cardiac death: identifying the roadblocks. Circulation. 2011;123:2423–30. doi: 10.1161/CIRCULATIONAHA.110.959734. [DOI] [PubMed] [Google Scholar]
  • 2.Al-Khatib SM, Stevenson WG, Ackerman MJ et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary. Circulation. 2018;138:272–391. doi: 10.1161/CIR.0000000000000548. [DOI] [PubMed] [Google Scholar]
  • 3.Priori SG, Blomström-Lundqvist C, Mazzanti A et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2015;36:2793–867. doi: 10.1093/eurheartj/ehv316. [DOI] [PubMed] [Google Scholar]
  • 4.Van Barreveld M, Dijkgraaf MGW, Hulleman M et al. Dutch outcome in implantable cardioverter-defibrillator therapy (DO-IT): Registry design and baseline characteristics of a prospective observational cohort study to predict appropriate indication for implantable cardioverter-defibrillator. Neth Heart J. 2017;25:574–80. doi: 10.1007/s12471-017-1016-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Sabbag A, Suleiman M, Laish-Farkash A et al. Contemporary rates of appropriate shock therapy in patients who receive implantable device therapy in a real-world setting: from the Israeli ICD Registry. Heart Rhythm. 2015;12:2426–33. doi: 10.1016/j.hrthm.2015.08.020. [DOI] [PubMed] [Google Scholar]
  • 6.Persson R, Earley A, Garlitski AC et al. Adverse events following implantable cardioverter defibrillator implantation: a systematic review. J Interv Card Electrophysiol. 2014;40:191–205. doi: 10.1007/s10840-014-9913-z. [DOI] [PubMed] [Google Scholar]
  • 7.Maisel WH, Moynahan M, Zuckerman BD et al. Pacemaker and ICD generator malfunctions analysis of Food and Drug Administration annual reports. JAMA. 2006;295:1901–6. doi: 10.1001/jama.295.16.1901. [DOI] [PubMed] [Google Scholar]
  • 8.Haanschoten DM, Elvan A, Ramdat Misier AR et al. Long-term outcome of the randomized DAPA trial. Circ Arrhythm Electrophysiol. 2020;13:e008484. doi: 10.1161/CIRCEP.120.008484. [DOI] [PubMed] [Google Scholar]
  • 9.Moss AJ, Greenberg H, Case RB et al. Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator. Circulation. 2004;110:3760–5. doi: 10.1161/01.CIR.0000150390.04704.B7. [DOI] [PubMed] [Google Scholar]
  • 10.Assaf A, Diletti R, Hoogendijk MG et al. Vulnerability for ventricular arrhythmias in patients with chronic coronary total occlusion. Expert Rev Cardiovasc Ther. 2020;18:487–94. doi: 10.1080/14779072.2020.1793671. [DOI] [PubMed] [Google Scholar]
  • 11.Ávila P, Pérez-David E, Izquierdo M et al. Scar extension measured by magnetic resonance-based signal intensity mapping predicts ventricular tachycardia recurrence after substrate ablation in patients with previous myocardial infarction. JACC Clin Electrophysiol. 2015;1:353–65. doi: 10.1016/j.jacep.2015.07.006. [DOI] [PubMed] [Google Scholar]
  • 12.Klem I, Weinsaft JW, Bahnson TD et al. Assessment of myocardial scarring improves risk stratification in patients evaluated for cardiac defibrillator implantation. J Am Coll Cardiol. 2012;60:408–20. doi: 10.1016/j.jacc.2012.02.070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Chew DS, Heikki H, Schmidt G et al. Change in left ventricular ejection fraction following first myocardial infarction and outcome. JACC Clin Electrophysiol. 2018;4:672–82. doi: 10.1016/j.jacep.2017.12.015. [DOI] [PubMed] [Google Scholar]
  • 14.Buxton AE, Lee KL, Hafley GE et al. Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery disease: lessons from the MUSTT study. J Am Coll Cardiol. 2007;50:1150–7. doi: 10.1016/j.jacc.2007.04.095. [DOI] [PubMed] [Google Scholar]
  • 15.Kini V, Soufi MK, Deo R et al. Appropriateness of primary prevention implantable cardioverter-defibrillators at the time of generator replacement: are indications still met? J Am Coll Cardiol. 2014;63:2388–94. doi: 10.1016/j.jacc.2014.03.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Younis A, Goldberger JJ, Kutyifa V et al. Predicted benefit of an implantable cardioverter-defibrillator: the MADIT-ICD benefit score. Eur Heart J. 2021;42:1676–84. doi: 10.1093/eurheartj/ehaa1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Buxton AE, Lee KL, Hafley GE et al. Relation of ejection fraction and inducible ventricular tachycardia to mode of death in patients with coronary artery disease: an analysis of patients enrolled in the multicenter unsustained tachycardia trial. Circulation. 2002;106:2466–72. doi: 10.1161/01.cir.0000037224.15873.83. [DOI] [PubMed] [Google Scholar]
  • 18.Bardy GH, Lee KL, Mark DB et al. Amiodarone or an implantable cardioverter–defibrillator for congestive heart failure. N Engl J Med. 2005;352:225–37. doi: 10.1056/NEJMoa043399. [DOI] [PubMed] [Google Scholar]
  • 19.Elayi CS, Charnigo RJ, Heron PM et al. Primary prevention of sudden cardiac death early post-myocardial infarction. Circ Arrhythmia Electrophysiol. 2017;10:e005194. doi: 10.1161/CIRCEP.117.005194. [DOI] [PubMed] [Google Scholar]
  • 20.Silverstein JR, Katritsis DG, Josephson ME. Use and abuse of internal cardioverter defibrillators for primary prevention. Arrhythm Electrophysiol Rev. 2012;1:46–50. doi: 10.15420/aer.2012.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Martens P, Nuyens D, Rivero-Ayerza M et al. Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction. Clin Res Cardiol. 2019;108:1074–82. doi: 10.1007/s00392-019-01440-y. [DOI] [PubMed] [Google Scholar]
  • 22.Buxton AE, Waks JW, Shen C, Chen PS. Risk stratification for sudden cardiac death in North America – current perspectives. J Electrocardiol. 2016;49:817–23. doi: 10.1016/j.jelectrocard.2016.07.018. [DOI] [PubMed] [Google Scholar]
  • 23.Steinbeck G, Andresen D, Seidl K et al. Defibrillator implantation early after myocardial infarction. N Engl J Med. 2009;361:1427–36. doi: 10.1056/NEJMoa0901889. [DOI] [PubMed] [Google Scholar]
  • 24.Hohnloser SH, Kuck KH, Dorian P et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med. 2004;351:2481–8. doi: 10.1056/NEJMoa041489. [DOI] [PubMed] [Google Scholar]
  • 25.Parkash R, MacIntyree C, Dorian P. Predicting sudden cardiac death after myocardial infarction: a great unsolved challenge. Circ Arrhythm Electrophysiol. 2021;14:e009422. doi: 10.1161/CIRCEP.120.009422. [DOI] [PubMed] [Google Scholar]
  • 26.Barsheshet A, Goldenberg I, Moss AJ et al. Effect of elapsed time from coronary revascularization to implantation of a cardioverter defibrillator on long-term survival in the MADIT-II trial. J Cardiovasc Electrophysiol. 2011;22:1237–42. doi: 10.1111/j.1540-8167.2011.02096.x. [DOI] [PubMed] [Google Scholar]
  • 27.Stone GW, Selker HP, Thiele H et al. Relationship between infarct size and outcomes following primary PCI patient-level analysis from 10 randomized trials. J Am Coll Cardiol. 2016;67:1674–83. doi: 10.1016/j.jacc.2016.01.069. [DOI] [PubMed] [Google Scholar]
  • 28.Adabag S, Patton KK, Buxton AE et al. Association of implantable cardioverter defibrillators with survival in patients with and without improved ejection fraction: secondary analysis of the sudden cardiac death in heart failure trial. JAMA Cardiol. 2017;2:767–74. doi: 10.1001/jamacardio.2017.1413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Piccini JP, Zhang M, Pieper K et al. Predictors of sudden cardiac death change with time after myocardial infarction: Results from the VALIANT trial. Eur Heart J. 2010;31:211–21. doi: 10.1093/eurheartj/ehp425. [DOI] [PubMed] [Google Scholar]
  • 30.Packer M. Major reduction in the risk of sudden cardiac death in patients with chronic heart failure with the use of drug and device combinations that favourably affect left ventricular structure. Eur J Heart Fail. 2019;21:823–6. doi: 10.1002/ejhf.1501. [DOI] [PubMed] [Google Scholar]
  • 31.Gupta A. Substrate imaging to guide primary prevention implantable cardioverter-defibrillator in ischemic cardiomyopathy: fanciful or realistic aim? JACC Cardiovasc Imaging. 2020;13:1767–70. doi: 10.1016/j.jcmg.2020.05.013. [DOI] [PubMed] [Google Scholar]
  • 32.Kwong RY, Chan AK, Brown KA et al. Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease. Circulation. 2006;113:2733–43. doi: 10.1161/CIRCULATIONAHA.105.570648. [DOI] [PubMed] [Google Scholar]
  • 33.Haghbayan H, Lougheed N, Deva DP et al. Peri-infarct quantification by cardiac magnetic resonance to predict outcomes in ischemic cardiomyopathy: prognostic systematic review and meta-analysis. Circ Cardiovasc Imaging. 2019;12:e009156. doi: 10.1161/CIRCIMAGING.119.009156. [DOI] [PubMed] [Google Scholar]
  • 34.Bulluck H, Hammond-Haley M, Weinmann S et al. Myocardial infarct size by CMR in clinical cardioprotection studies: insights from randomized controlled trials. JACC Cardiovasc Imaging. 2017;10:230–40. doi: 10.1016/j.jcmg.2017.01.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Ibanez B, Aletras AH, Arai AE et al. Cardiac MRI endpoints in myocardial infarction experimental and clinical trials: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019;74:238–56. doi: 10.1016/j.jacc.2019.05.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Acosta J, Fernández-Armenta J, Borràs R et al. Scar characterization to predict life-threatening arrhythmic events and sudden cardiac death in patients with cardiac resynchronization therapy: the GAUDI-CRT study. JACC Cardiovasc Imaging. 2018;11:561–72. doi: 10.1016/j.jcmg.2017.04.021. [DOI] [PubMed] [Google Scholar]
  • 37.Saeed M, Lund G, Wendland MF et al. Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media. Circulation. 2001;103:871–6. doi: 10.1161/01.cir.103.6.871. [DOI] [PubMed] [Google Scholar]
  • 38.Karim R, Bhagirath P, Claus P et al. Evaluation of state-of-the-art segmentation algorithms for left ventricle infarct from late gadolinium enhancement MR images. Med Image Anal. 2016;30:95–107. doi: 10.1016/j.media.2016.01.004. [DOI] [PubMed] [Google Scholar]
  • 39.Cheniti G, Sridi S, Sacher F et al. Post–myocardial infarction scar with fat deposition shows specific electrophysiological properties and worse outcome after ventricular tachycardia ablation. J Am Heart Assoc. 2019;8:e012482. doi: 10.1161/JAHA.119.012482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Saba S, Adelstein E, Wold N et al. Influence of patients’ age at implantation on mortality and defibrillator shocks. Europace. 2017;19:802–7. doi: 10.1093/europace/euw085. [DOI] [PubMed] [Google Scholar]
  • 41.Sun Y, Kiani MF, Postlethwaite AE, Weber KT. Infarct scar as living tissue. Basic Res Cardiol. 2002;97:343–7. doi: 10.1007/s00395-002-0365-8. [DOI] [PubMed] [Google Scholar]
  • 42.Arai AE. Healing after myocardial infarction: a loosely defined process. JACC Cardiovasc Imaging. 2015;8:680–3. doi: 10.1016/j.jcmg.2015.02.012. [DOI] [PubMed] [Google Scholar]
  • 43.Sánchez-Somonte P, Quinto L, Garre P et al. Scar channels in cardiac magnetic resonance to predict appropriate therapies in primary prevention. Heart Rhythm. 2021;18:1336–43. doi: 10.1016/j.hrthm.2021.04.017. [DOI] [PubMed] [Google Scholar]
  • 44.Selvanayagam JB, Hartshorne T, Billot L et al. Cardiovascular magnetic resonance-GUIDEd management of mild to moderate left ventricular systolic dysfunction (CMR GUIDE): Study protocol for a randomized controlled trial. Ann Noninvasive Electrocardiol. 2017;22:e12420. doi: 10.1111/anec.12420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Moss AJ, Fadl Y, Zareba W et al. Survival benefit with an implanted defibrillator in relation to mortality risk in chronic coronary heart disease. Am J Cardiol. 2001;88:516–20. doi: 10.1016/s0002-9149(01)01729-5. [DOI] [PubMed] [Google Scholar]
  • 46.Priori SG, Blomstrom-Lundqvist C, Mazzanti A et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2015;36:2793–67. doi: 10.1093/eurheartj/ehv316. [DOI] [PubMed] [Google Scholar]
  • 47.Disertori M, Masè M, Rigoni M et al. Ventricular tachycardia-inducibility predicts arrhythmic events in post-myocardial infarction patients with low ejection fraction. A systematic review and meta-analysis. Int J Cardiol Heart Vasc. 2018;20:7–13. doi: 10.1016/j.ijcha.2018.06.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Buxton AE, Lee KL, Fisher JD et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med. 1999;341:1882–90. doi: 10.1056/NEJM199912163412503. [DOI] [PubMed] [Google Scholar]
  • 49.Zaman S, Taylor AJ, Stiles M et al. Programmed ventricular stimulation to risk stratify for early cardioverter-defibrillator implantation to prevent tachyarrhythmias following acute myocardial infarction (PROTECT-ICD): trial protocol, background and significance. Heart Lung Circ. 2016;25:1055–62. doi: 10.1016/j.hlc.2016.04.007. [DOI] [PubMed] [Google Scholar]

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