Author + information
- Published online March 19, 2018.
- Noel G. Boyle, MD, PhD∗ ( and )
- Duc H. Do, MD
- UCLA Cardiac Arrhythmia Center, UCLA Health System, David Geffen School of Medicine at UCLA, Los Angeles, California
- ↵∗Address for correspondence:
Dr. Noel G. Boyle, UCLA Cardiac Arrhythmia Center, David Geffen School of Medicine at UCLA, 100 UCLA Medical Plaza, Suite 660, Los Angeles, California 90095-7392.
End-stage renal disease (ESRD) patients on hemodialysis are at high risk for mortality, with age-adjusted survival of 42% at 5 years after initiation of hemodialysis (1). Cardiovascular disease accounts for 54% of deaths in this population, with sudden death or arrhythmias accounting for almost 39% of total deaths in the US dialysis population (1).
Ventricular tachycardia (VT) and ventricular fibrillation (VF) have been regarded as the primary cause of sudden cardiac death in ESRD patients (2,3). Holter studies, lasting 24 to 48 h, have shown a high prevalence of ventricular arrhythmias, primarily premature ventricular contractions and runs of nonsustained ventricular tachycardia, during and after dialysis sessions (4,5). Other studies have also shown VT or VF as a presenting rhythm in 53% to 70% of patients who experience sudden death in a dialysis unit (6–8). It has been postulated that rapid electrolyte and volume shifts, especially after the 2- to 3-day interdialytic interval (6,9,10), ischemia, inflammation, and sympathetic activation from dialysis combined with a vulnerable underlying myocardial substrate with areas of fibrosis contribute to the risk of sudden death (2,3).
Current recommendations to reduce sudden death risk include use of beta blockers, avoidance of low-potassium dialysates, implantable cardioverter-defibrillators (ICDs) where appropriate, and availability of automated external defibrillators on site at all dialysis centers (11); however, it is questionable whether these therapies are effective in this patient population. Lehrich et al. (7), in a study of 729 patients who developed cardiac arrest in US dialysis centers between 2002 and 2005, found no difference in sudden death survival in dialysis units with and without automated external defibrillators. Herzog et al. (12), in a retrospective analysis of a Medicare database consisting of 6,042 dialysis patients who survived a cardiac arrest between 1996 and 2001, found that those who had an ICD implanted within 30 days of the hospital admission (460; 7.6%) had a 42% reduction in mortality over 5 years compared with a propensity-matched cohort without ICD implantation. It is unclear how many of these patients had VT/VF, because only one-quarter of the total underwent cardiovascular workup, and it is well known that patients with bradycardic or pulseless electrical activity arrests have worse survival (12). In addition, dialysis patients are at high risk for device infections, which can cause significant morbidity and mortality (13). These findings raise the question of what the actual mechanism of sudden death is in these patients and what additional opportunities for prevention are possible.
Sacher et al. (14), in a study published in this issue of JACC: Clinical Electrophysiology, addressed this question by placing implantable loop recorders in 71 patients (mean age 65 ± 9 years; 73% male) undergoing maintenance dialysis for ESRD (median duration of 19 months before enrollment) at 8 dialysis centers in France. The patients were followed up for at least 18 months with remote monitoring transmissions sent weekly during their hemodialysis sessions. They excluded patients with pre-existing implanted pacemakers or ICDs. The initial target enrollment of 100 patients was not reached because of reported low rates of acceptance in the study population. The authors evaluated transmitted recordings for arrhythmias, including significant ventricular arrhythmias, bradycardic rhythms, and atrial fibrillation, and then applied a frailty survival model to assess for risk factors, including time-varying covariates and recurrent arrhythmic events, for each type of arrhythmia.
During the follow-up period, 16 patients (23%) died, with 5 of these deaths deemed cardiac related. Four of these were sudden deaths, and 1 patient had a myocardial infarction with pulseless electrical activity. Interestingly, in none of the sudden cardiac arrest patients was the terminal rhythm VT/VF; in 3 of 4, bradycardia leading to asystole was seen. The cause was severe metabolic acidosis in the fourth patient, admitted for surgery; no specific cause could be found in the other 3 patients. Of the 11 patients who experienced noncardiac death, 7 died of sepsis, 2 of stroke or its complications, 1 of massive hemorrhage, and 1 after withdrawal of care for terminal illness.
The authors also found that 16 patients (23%) had a significant conduction disorder event, including those who had sudden death; 10 (14%) had significant ventricular arrhythmias (all nonsustained VT), and 14 patients (20%) without pre-existing atrial fibrillation were diagnosed with atrial fibrillation at a median of 6.7 months from implantation. A pacemaker was implanted in 3 patients with significant rhythm disorders, although the particular rhythm in these cases and associated symptoms were not specified. No cardiovascular pathogenesis, specifically coronary artery disease, was identified in any patient with significant ventricular arrhythmias despite thorough workup. Eight of the patients with newly diagnosed atrial fibrillation were initiated on anticoagulation therapy.
In a multivariate analysis, the authors found that significant conduction disorders were associated with potassium >5.0 mmol/l, bicarbonate <22 mmol/l, longer interdialytic period, diabetes mellitus, history of coronary disease, and other cardiac arrhythmias during follow-up. Significant ventricular arrhythmias were associated with the presence of other cardiac arrhythmias during follow-up, potassium <4 mmol/l, and lack of beta-blocker therapy. Atrial fibrillation was associated with potassium level <4 mmol/l and serum phosphate >1.45 mmol/l. From these results, the authors highlight that tight potassium control, between 4 and 5 mmol/l, is of critical importance in preventing all types of arrhythmias.
The finding of new, often asymptomatic episodes of atrial fibrillation in 20% of the patients, although not as dramatic as sudden death, might be the most actionable finding from this study. ESRD patients are at particularly high risk for atrial fibrillation from fluid shifts and underlying cardiovascular disease. Hence, its diagnosis and appropriate management with anticoagulation might be the most beneficial in decreasing long-term cardiovascular morbidity and mortality from stroke and systemic embolism, which currently account for 3% of deaths in ESRD patients (1).
This study is the first to monitor the actual terminal rhythm before sudden death in ESRD patients. However, the number of sudden death events was low, possibly in part because of the relatively short duration of dialysis therapy in the patient population before enrollment and the selection of patients with less severe cardiac disease, given the exclusion of patients with pre-existing pacemakers and ICDs. Although it is interesting to note that none of the terminal rhythms in these patients were VT/VF, this is likely attributable to chance alone, given the small number studied. The authors could not find a specific cause for 3 of the episodes of severe bradycardia leading to sudden death, but it is possible that a primary respiratory event (such as aspiration) or a metabolic derangement such as acidosis or severe hypoglycemia was the triggering cause. Although commonly classified as cardiac death for lack of evidence to the contrary, the underlying causes might not actually be cardiovascular in nature.
Although almost 40% of deaths of ESRD patients are sudden, this study by Sacher et al. (14) reminds us that many might be bradycardic related, and prevention efforts must be expanded beyond VT/VF detection and treatment. A larger study, possibly using the recently developed very small implantable loop recorders (15), which are easily implanted percutaneously, is needed to elucidate the causes of sudden death in these patients before we can actually put into place more effective practices.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- 2018 American College of Cardiology Foundation
- United States Renal Data System
- Gruppo Emodialisi e Patologie Cardiovasculari
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