Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease

Introduction

In 2014, approximately 30,000 patients on dialysis in the United States, died due to sudden cardiac death (SCD) (1). The risk of SCD after starting dialysis (10%) is comparable with the risk in the postmyocardial infarction period (8%) and among patients with heart failure with reduced ejection fraction (6%), and it is 100-fold higher than in the general population (0.1%) (1–3). SCD is commonly defined as death without an obvious noncardiac cause in people who were apparently well during the last 24 hours. SCD is often assumed to be due to ventricular tachycardia/ventricular fibrillation (VT/VF). Preventing SCD requires knowledge of the arrhythmic mechanism causing SCD. For instance, patients with heart failure with reduced ejection fraction have a higher risk of SCD death due to VT/VF, which is substantially reduced with implantable cardioverter defibrillators. However, implantable cardioverter defibrillators are not effective if SCD is due to mechanisms other than VT/VF. Lack of knowledge of arrhythmias contributing to SCD in patients on dialysis has been a significant barrier to preventing SCD in this population.

Recent Therapeutic Advances

The availability of miniaturized leadless implantable cardiac monitors (ICMs) with high patient acceptability (4) is a paradigm-changing advance. The ICM is placed subcutaneously over the precordium under local anesthesia with a small (<1-cm) incision and takes <2 minutes to implant. The ICM continuously records arrhythmic events for 3–4 years. Data are transmitted daily by a base unit at the patient’s home via secure wireless connection. In addition, manual transmissions can be initiated for symptomatic episodes. Detected arrhythmias generate alerts that are reviewed daily at cardiology device clinics. The ICM can also be interrogated by devices available in emergency departments. The ICMs are Food and Drug Administration-cleared for patients at high risk for arrhythmias or those with symptoms suggestive of arrhythmias (for example, palpitations, dizziness, and syncope). Patients on dialysis constitute one of the highest risk groups for arrhythmias and SCD. ICM placement is covered by Medicare and most commercial insurances (Current Procedural Terminology code: 33282). Reimbursement includes a physician professional fee (approximately $200) and a procedure fee for the hospital or surgical center (approximately $6000), which includes the cost of the ICM. The monitoring process does not add any burden to the dialysis clinics.

Studies using ICM are challenging the assumption that VT/VF is the major mechanism of SCD in patients on dialysis. In a study of 100 patients on hemodialysis in Brazil with ICMs, there were seven SCDs during follow-up. Four of seven deaths were due to arrhythmias, one was due to VT/VF, and three were due to bradyarrhythmias (5). Among 50 patients on hemodialysis in Australia with ICMs, there were eight SCDs—all were due to bradyarrhythmias (6). Similarly, among 71 patients on hemodialysis in France with ICMs, there were four SCDs, all due to bradyarrhythmias (7). Higher serum potassium (>5.0 mEq/L) was associated with bradyarrhythmias, and low serum potassium (<4.0 mEq/L) was associated with ventricular tachycardia. In addition, among 30 patients on hemodialysis in the United Kingdom with ICMs, there were two sudden deaths (one due to VT/VF), but bradyarrhythmias were common, and three patients required pacemakers (8). Finally, the Monitoring in Dialysis Study followed 66 patients on hemodialysis with ICMs in the United States and India (9). Bradyarrhythmias were common, and 8% of the patients required a pacemaker. Notably, many bradyarrhythmias were related to β-blocker use. Routine clinical parameters were not useful for identifying patients at risk for arrhythmias.

Overall, these studies from six different countries all point to the role of bradyarrhythmias rather than VT/VF in SCD in patients on dialysis. These studies also highlight that ICMs are safe and provide invaluable information to individualize patient management, including interventions that potentially prevented SCD.

Clinical Implication of Recent Advances

A major implication of these studies is that SCD in patients on dialysis might be preventable by ICM-guided personalized management of arrhythmias. Although bradyarrhythmias may be a major mechanism for SCD, the arrhythmias causing SCD may change over time after dialysis initiation (Figure 1). Notably, prior studies included only patients on dialysis for some time (prevalent patients) so their findings may not be generalizable to patients starting dialysis (incident patients). VT/VF may be predominant in incident patients with vulnerable myocardium (undiagnosed cardiomyopathy/ischemia) experiencing intradialytic myocardial stunning and electrolyte abnormalities. Among survivors (prevalent patients; as in published studies), conduction system fibrosis and calcification may contribute to the higher risk of bradyarrhythmias, which are worsened by hyperkalemia and β-blockers.

Figure 1.

A person-centered paradigm to prevent sudden cardiac death guided by data from implantable cardiac monitors. In the lower panel, the graph depicts the cumulative survival of patients on dialysis. Potential arrhythmias contributing to the mortality are presented. The mechanism of sudden death early after dialysis initiation is unknown and could be due to ventricular tachycardia/ventricular fibrillation (VT/VF) or bradyarrhythmias. Electrolyte abnormalities likely contribute to sudden death at any point of time after dialysis initiation. Studies outlined in the text highlight the risk of bradyarrhythmias as a mechanism for sudden death in patients on dialysis for longer period of time. Potential interventions to reduce risk of sudden death are presented in the upper left and upper right panels. RKF, residual kidney function.

Continuous cardiac monitoring using ICMs should thus become the standard of care in patients on dialysis, and it should be used routinely in all patients on dialysis unless there are contraindications (active infection or coagulopathy) or if the dialysis is considered palliative. In particular, for patients in whom dialysis is a “bridge” to transplantation, ICMs should be considered high priority, and they should be implanted before dialysis initiation, guiding management in the first 90 days of dialysis, a period with the highest risk of SCD.

An ICM-guided management approach uses established management strategies after arrhythmias are detected. For example, patients with recurrent ventricular tachycardia (Figure 1, upper left panel) require diagnostic workup and correction of myocardial ischemia, use of β-blockers, and optimization of serum electrolytes. For patients with residual kidney function, incremental dialysis can reduce hemodynamic/metabolic stress. Patients with bradyarrhythmias (Figure 1, upper right panel) benefit from reduction or discontinuation of β-blockers, management of hyperkalemia (dietary modification and use of potassium binding resins), and consideration of pacemaker implantation.

This paradigm change is feasible but requires new educational approaches to facilitate discussion between patients and physicians about the high risk of SCD and its prevention. New system-based approaches include risk assessment as part of the standard CKD “Assessment and Plan,” the monthly “Dialysis Comprehensive Note,” and nursing assessments. The Centers for Medicare and Medicaid Services can facilitate this process by including a management plan for preventing SCD in patients on dialysis as a quality of care metric.

High-Priority Areas for Research

Data from ICMs will be critical to guiding future research to prevent SCD in patients on dialysis. The use of device therapies for primary/secondary prevention of SCD in patients on dialysis is controversial due to the lack of data on the arrhythmias causing SCD, inability to identify high-risk subgroups, perception of futility, transvenous lead infections, and loss of vascular access. Data from ICMs will allow identification of patient subgroups at highest risk for SCD, setting the stage for randomized, controlled trials of prevention. Possible device strategies may include extravascular defibrillators and intracardiac pacemakers.

Although we suggest routine use of ICMs, we are cognizant of the costs. However, the ICM cost may be more than offset by reducing just one hospitalization (for example, syncope due to bradycardia or flash pulmonary edema due to atrial fibrillation). Formal cost-benefit analyses with input from all stakeholders, including patients, are needed to address this issue.

Finally, ICMs also offer an opportunity for new educational research. Nephrology fellowships could test a specialized “Cardiorenal” curriculum, which includes procedural skills for ICM placement and management of arrhythmias, in addition to specialized training in heart failure proposed previously (10).

In conclusion, rapid technologic advances in the past decade are poised to help us understand the types of arrhythmias contributing to SCD in patients on dialysis. These advances provide an unprecedented opportunity to develop innovative paradigms of care and address the major cause of mortality in patients on dialysis.

Disclosures

T.S. is a member of the Clinical Journal of the American Society of Nephrology Editorial Board.