In this issue of Polish Archives of Internal Medicine (Pol Arch Intern Med), Winkler et al1 identify predictors of mortality and appropriate interventions in implantable cardioverter-defibrillator (ICD) recipients. This is important because the extent to which individual patients benefit from an ICD varies considerably.2
The study group included primary and secondary prevention device recipients. It is unsurprising that secondary prevention patients received more appropriate ICD interventions for ventricular arrhythmias. Although some programming features are noted, there is no breakdown of therapies into antitachycardia pacing (ATP) and shock delivery. Taken as a group, patients who received shocks had higher ventricular arrhythmia burden and poorer survival than patients treated only with ATP.3 In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) post hoc analysis, shocks (appropriate or not) were associated with poorer survival in patients with ICDs.4,5 This has spurred interest in shock reduction without increasing syncope or sudden cardiac death (SCD) rates. Shocks can be reduced by appropriate programming,4,6 allowing longer detection times and longer arrhythmia duration before shock delivery. The MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy) demonstrated that such programming can be associated with improved patient survival.4,7 Strategic programming of ICD tachycardia detection and therapies is therefore recommended.4,6
Although Winkler et al1 found that cardiac resynchronization therapy (CRT) reduced the risk of appropriate ICD therapy in primary prevention, the influence of CRT on ventricular arrhythmias is uncertain. While some studies suggest a proarrhythmic effect, others suggest an antiarrhythmic effect. In particular, it remains unclear whether CRT reduces ventricular arrhythmias via reverse remodeling or whether resynchronization and shortening ventricular activation time confers a persistent antiarrhythmic effect.8 The MADIT-CRT and a recent meta-analysis8-10 provide evidence that CRT-mediated left ventricular improvement is antiarrhythmic. In the absence of reverse remodeling, CRT with left ventricular epicardial stimulation may be proarrhythmic.11 Recent data suggest that CRT may be antiarrhythmic in primary prevention recipients and proarrhythmic in secondary prevention recipients.8
The authors of the study stated that “in the long-term follow-up, previous myocardial infarction was also predictor of ICD interventions.”1 It is tempting to speculate that ongoing ischemia could explain this finding. Nevertheless, this differs from a 2010 study that reported no significant difference in the incidence of appropriate ICD shocks in patients with ischemic versus nonischemic cardiomyopathy at the 33-month follow-up.12
Winkler et al1 correctly noted that understanding the relationship between severe mitral regurgitation and appropriate device therapy is challenging. The major causes of severe mitral regurgitation include primary valvular diseases (most commonly mitral valve prolapse)13 and secondary (functional) valvular dysfunction due to coronary artery disease or cardiomyopathy.14 The precise relationship between mitral valve prolapse and SCD remains uncertain and the increased SCD risk may be related to the valvular regurgitation rather than the abnormality in the valve’s structural apparatus.15 While secondary mitral regurgitation is associated with poor prognosis beyond the degree of left ventricular dysfunction, survival rates vary inversely with mitral regurgitation severity,16 and death may be related to hemodynamic failure or a sudden arrhythmic event.17 Mitral valve repair or replacement may improve symptoms of secondary mitral regurgitation, but there is no evidence that it improves survival.16 CRT recipients with severe mitral regurgitation have higher mortality rates, and persistent moderate to severe mitral regurgitation post-CRT has been associated with poorer clinical outcomes (survival rates are higher with mitral regurgitation improvement),16,18 a higher incidence of arrhythmic events, and less reverse remodeling.19,20
It is not surprising that the authors found that “total mortality is strongly affected by comorbidities and natural course of heart failure.”1 ICD therapy is hardly a panacea. Reeder et al2 pointed out that weighing the inconvenience and risks of living with an ICD against an expected survival advantage is often far from straightforward. Many ICD recipients are older patients with multiple comorbidities and individual choices between extended survival, ICD shocks, and quality of life may not be clear-cut.2 They performed a secondary analysis of the ICD recipients from the SCDHeFT and applied an illness-death regression model to concurrently model both ICD shocks and death to help predict each patient’s probability of having received ICD shocks, dying, or both at any given point in time. If validated, their tool may be useful for individualized counseling regarding likely outcomes after device implantation.2
While laudable, the current study reminds us that our ability to predict individual outcomes of ICD therapy remains incomplete. Although there is more work to be done, motivation to provide optimal patient care will continue to propel us in the right direction.
Richard G. Trohman, MD, MBA, Rush University Medical Center, 1653 W. Congress Parkway Room 301 Kellogg, Chicago, IL 60612, United States, phone: +13129422887, email: rtrohman@rush.edu
September 4, 2019.
September 5, 2019.
October 30, 2019.
The opinions expressed by the author are not necessarily those of the journal editors, Polish Society of Internal Medicine, or publisher.
None declared.
Trohman RG. Predicting appropriate therapies and mortality in implantable cardioverter-defibrillator recipients: a work in progress. Pol Arch Intern Med. 2019; 129: 657-658. doi:10.20452/pamw.15038
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- Winkler A, Jaguś-Jamioła A, Uziębło-Życzkowska B, et al. Predictors of appropriate interventions and mortality in patients with implantable cardioverter-defibrillators. Pol Arch Intern Med. 2019; 129: 667-672.Crossref
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- Reeder HT, Shen C, Buxton AE, et al. Joint shock/death risk prediction model for patients considering implantable cardioverter-defibrillators. Circ Cardiovasc Qual Outcomes. 2019; 12: e005675.Crossref
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- Wilkoff BL, Fauchier L, Stiles MK, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm. 2016; 13: e50-e86.
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- Moss AJ, Schuger C, Beck CA, et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med. 2012; 367: 2275-2283.Crossref
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- Ruwald MH, Solomon SD, Foster E, et al. Left ventricular ejection fraction normalization in cardiac resynchronization therapy and risk of ventricular arrhythmias and clinical outcomes: results from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial. Circulation. 2014; 130: 2278-2286.Crossref
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- Gaasch, WH. Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet. https://www.uptodate.com/contents/natural-history-of-chronic-mitral-regurgitation-caused-by-mitral-valve-prolapse-and-flail-mitral-leaflet. Updated January 10, 2018. Accessed October 3, 2019.
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- Sorrentino, MJ. Arrhythmic complications of mitral valve prolapse. https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse. Updated September 20, 2017. Accessed October 3, 2019.
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- Gaasch, WH. Management and prognosis of chronic secondary mitral regurgitation. https://www.uptodate.com/contents/management-and-prognosis-of-chronic-secondary-mitral-regurgitation. Updated February 8, 2019. Accessed October 3, 2019.
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- Kligfield P, Hochreiter C, Niles N, et al. Relation of sudden death in pure mitral regurgitation, with and without mitral valve prolapse, to repetitive ventricular arrhythmias and right and left ventricular ejection fractions. Am J Cardiol. 1987; 60: 397-399.Crossref
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- van Bommel RJ, Marsan NA, Delgado V, et al. Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk. Circulation. 2011; 124: 912-919.Crossref
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- Cabrera-Bueno F, Molina-Mora MJ, Alzueta J, et al. Persistence of secondary mitral regurgitation and response to cardiac resynchronization therapy. Eur J Echocardiogr. 2010; 11: 131-137.Crossref