Author + information
- Michael C.G. Wong, MBBS,
- Jonathan M. Kalman, PhD,
- Eugenia Pedagogos, PhD,
- Nigel Toussaint, PhD,
- Jitendra K. Vohra, MD,
- Paul B. Sparks, PhD,
- Prashanthan Sanders, PhD,
- Peter M. Kistler, PhD,
- Karen Halloran, RN,
- Geoffrey Lee, PhD,
- Stephen A. Joseph, PhD and
- Joseph B. Morton, PhD∗ ()
- ↵∗Department of Cardiology, Royal Melbourne Hospital, Grattan Street, Parkville, Melbourne, 3050, Australia
Patients with chronic kidney disease (CKD) undergoing hemodialysis experience a high annual mortality rate (7% per year) with 25% of all deaths due to sudden cardiac death (SCD) (1). There has been conjecture as to the mechanism of SCD.
This prospective study (Identification and Characterisation of Risk Factors for Atrial and Ventricular Arrhythmias in Chronic Kidney Disease Patients Using Implantable Cardiac Monitoring; ACTRN12613001326785) aimed to document the arrhythmic mechanism of SCD in a cohort of CKD patients with preserved left ventricular (LV) function on hemodialysis using an implantable cardiac monitor (ICM). We recruited 50 clinically stable ambulatory CKD patients receiving stable outpatient thrice-weekly hemodialysis. Exclusion criteria included severe LV dysfunction (LV ejection fraction <35%), New York Heart Association class IV symptoms, pre-existing pacemaker or implantable cardioverter-defibrillator in situ, and a previous history of clinical ventricular tachyarrhythmias or syncope. Each patient had an ICM (Confirm, St. Jude Medical, St. Paul, Minnesota) implanted subcutaneously over the left upper chest for continuous electrocardiographic monitoring.
Storage of the electrocardiogram was triggered automatically when arrhythmic events fulfilled pre-programmed cutoff criteria, including the following: 1) sinus bradycardia ≤40 beats/min for ≥4 beats; 2) sinus arrest with pauses/asystole ≥3 s; 3) high-degree atrioventricular (AV) block (second- to third-degree AV block) ≤40 beats/min lasting ≥3 s; 4) nonsustained ventricular tachycardia (VT) ≥125 beats/min, >16 beats lasting <30 s); 5) sustained VT ≥125 beats/min, lasting ≥30 s; and 6) ventricular fibrillation.
Arrhythmias were characterized by their temporal occurrence relative to hemodialysis sessions. The long interdialytic period (LIDP) was defined as the 72-h break between hemodialysis sessions, whereas the other two 48-h IDP were each defined as the short interdialytic period (SIDP). Conventional thrice-weekly hemodialysis includes a single LIDP and 2 SIDPs. Patients underwent intensive follow-up every 2 weeks for device data download.
The arrhythmic event data were positively skewed, so a logarithmic transformation of the data was performed prior to analysis to ensure homogeneity of variance. Analysis of variance with repeated measures was then performed comparing incidence rates between each day.
The mean age of the study population was 66 ± 11 years and 72% of the population was male. Participants had been receiving hemodialysis for a mean of 5 ± 4 years. Comorbidities included diabetes mellitus in 58%, hypertension in 86%, LV hypertrophy in 48%, and ischemic heart disease in 48% of the population. All study participants had a LV ejection fraction >35%, and 58% had a LV ejection fraction >60%. Only 6% had QRS duration >120 ms. Of the total participants, 72% were taking a beta-blocker. Seven patients had known atrial fibrillation prior to ICM implantation (3 paroxysmal, 4 permanent).
After a mean follow-up of 12 ± 4 months, there were 6 deaths (12%); 5 deaths were unexpected and classified as SCD. There was 1 non-SCD due to multiorgan failure after elective orthopedic surgery. Of the 5 SCD patients, 2 underwent post-mortem examinations that failed to identify an acute cause of death. Another individual with witnessed out-of-hospital SCD died within 24 h of hospital admission and extensive investigation did not establish a cause of death. All SCD events occurred during the LIDP with severe bradycardia and ensuing asystole in 4 cases recorded by the ICM as the terminal event (Figure 1). ICM interrogation in the fifth case was refused due to cultural reasons. No ventricular arrhythmias were recorded either preceding or following the bradycardic event in any of the 4 cases. In the 5 patients, the longest recorded pause prior to the SCD event was 2 s with no reported episodes of high-grade AV block or syncope. In addition, there was no evidence of QRS widening accompanying bradycardia in the initial phase of the event in any of the 4 patients with recorded bradycardia at the time of death.
An additional patient was successfully resuscitated after experiencing an in-hospital cardiac arrest with sustained monomorphic VT after presenting with an acute coronary syndrome. There were no cases of polymorphic VT or ventricular fibrillation recorded. There were 1,488 significant arrhythmia events occurring in 22 patients (44%): bradycardia in 12 (24%); sinus arrest in 10 (20%); 2° AV block in 2 (4%); and nonsustained VT in 8 (16%). The final day of the LIDP had more events than all other days (p < 0.001 by analysis of variance).
In CKD patients on hemodialysis who have preserved LV function, our study demonstrates for the first time that the vast majority of SCD are due to bradycardia and asystole, rather than malignant ventricular arrhythmias. These observations raise the key question of whether bradycardia/asystole as the terminal rhythm represents a primary electrical event, or alternatively, a manifestation of end-stage, irreversible myocardial failure in the setting of profound biochemical, metabolic, and structural disarray. These observations have potential implications for strategies to minimize SCD in this population, the prescription of hemodialysis to minimize the LIDP, and the role of beta-blockers in CKD.
Please note: This study was supported by a research grant from St. Jude Medical. Dr. Wong is the recipient of the Keith Goldsbury Postgraduate Research Scholarship Award (ID: PC11M 6218) from the National Heart Foundation of Australia. Dr. Kalman has received research support from St. Jude Medical, Medtronic Inc., Biosense Webster, and Boston Scientific. Dr. Pedagogos has received honoraria and research grants from Shire and Amgen. Dr. Sanders has served on the advisory boards of Biosense Webster, Medtronic, St. Jude Medical, Sanofi, and Merck, Sharpe and Dohme; has received lecture fees from Biosense Webster, Medtronic, St. Jude Medical, Boston Scientific, Biotronik, Sanofi, and Merck, Sharpe and Dohme; has received research funding from Medtronic, St. Jude Medical, Boston Scientific, Biotronik, and Sorin; is supported by a Practitioner Fellowship from the National Health and Medical Research Council of Australia; and is supported by the National Heart Foundation of Australia. Dr. Morton has received research support from St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- U.S. Renal Data System