Cardiac Arrhythmia in Patients With End-Stage Renal Disease

Study Overview
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Brief Summary
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The study will examine the presence of cardiac arrhythmias in patients receiving hemodialysis and the role of diabetes, hypoglycemia and parameters related to uremia and the dialysis procedure. The study is designed as a prospective cohort study with 18 months follow-up. 70 patients receiving chronic hemodialysis will be recruited and equipped with implantable loop recorders (ILR): 35 patients with diabetes and 35 patients without diabetes. Data collection during the follow-up includes continuous monitoring of the heart rhythm by the ILR for the entire follow-up period, continuous glucose monitoring for 10 days every second month, and monthly collection of blood samples and dialytic parameters.

Official Title
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Cardiac Arrhythmia in Patients With End-Stage Renal Disease

Conditions
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End Stage Renal Disease on Dialysis, Cardiac Arrhythmia, Diabetes Mellitus, Hypoglycemia

Intervention / Treatment
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* Device: Loop recorder (Reveal LINQ, Medtronic)
* Device: Continuous Glucose Measurement (G6, Dexcom)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with diabetes: Type 1 diabetes or Type 2 diabetes diagnosed according to the criteria of the World Health Organization Treated with glucose-lowering drugs at inclusion Receiving in-center maintenance hemodialysis for more than 3 months Age ≥ 18 years Patients without diabetes: No known diagnosis of diabetes No previous treatment with glucose-lowering drugs HbA1c < 48 mmol/mol at screening Receiving in-center maintenance hemodialysis for more than 3 months Age ≥ 18 years Exclusion Criteria: For both groups: Cardiac pacemaker or implantable cardioverter defibrillator (ICD) Known permanent (chronic) atrial fibrillation History of sustained (> 30 seconds) ventricular tachycardia (more than 200 bpm) or ventricular fibrillation (note that ventricular premature beats is not considered an exclusion criterion) Known cardiac ion-channel disease (such as Long QT syndrome and Brugada syndrome) Not suitable for implantation (left-sided dialysis catheter or other condition expected to interfere with implantation) Previously complications in relation to wearing a CGM sensor, e.g. allergic reaction Inability to give written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients receiving hemodialysis with diabetes<br>Patients receiving chronic hemodialysis with a diagnose of Type 1 diabetes or Type 2 diabetes (diagnosed according to the criteria of the World Health Organization) and receiving glucose-lowering treatment | Device: Loop recorder (Reveal LINQ, Medtronic)<br>* Implantation of a loop-recorder<br>Device: Continuous Glucose Measurement (G6, Dexcom)<br>* Monitoring with a continuous glucose monitor<br>|
| Patients receiving hemodialysis without diabetes<br>Patients receiving chronic hemodialysis without diabetes (no known diagnosis of diabetes, and HbA1c < 48 mmol/mol at inclusion) | Device: Loop recorder (Reveal LINQ, Medtronic)<br>* Implantation of a loop-recorder<br>Device: Continuous Glucose Measurement (G6, Dexcom)<br>* Monitoring with a continuous glucose monitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically significant arrhythmias | Presence of one of the items in the combined endpoint of clinically significant arrhythmias defined as: Significant bradyarrhythmia (pause > 3 seconds or ≥ 4 beats at rate < 30 beats/min) Ventricular tachycardia (lasting ≥ 16 beats at rate ≥ 150 beats/min) Ventricular fibrillation | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial fibrillation | Presence of atrial fibrillation (lasting ≥ 2 minutes) | 18 months | 
| Supraventricular tachycardia other than atrial fibrillation | Presence of supraventricular tachycardia other than atrial fibrillation (lasting ≥ 16 beats at rate ≥ 150 beats/min) | 18 months | 
| Time to clinically significant arrhythmias, atrial fibrillation, or supraventricular tachycardia, respectively | Time to clinically significant arrhythmias, atrial fibrillation, or supraventricular tachycardia, respectively | 18 months | 
| Characterization of arrhythmias in terms of onset | Characterization of arrhythmias in terms of onset | 18 months | 
| Characterization of arrhythmias in terms of duration | Characterization of arrhythmias in terms of duration | 18 months | 
| Characterization of arrhythmias in terms of ventricular rate | Characterization of arrhythmias in terms of ventricular rate | 18 months | 
| Episodes of hypoglycemia | Episodes of hypoglycemia <3.9 mmol/L (defined as sensor glucose below 3.9 mmol/L for ≥ 15 min) | 18 months | 
| Time in range | Time in range (percentage of time and amount of time with sensor glucose in range 3.9-10.0 mmol/L) | 18 months | 
| Time below range (<3.9 mmol/L) | Time below range (percentage time and amount of time with sensor glucose <3.9 mmol/L) | 18 months | 
| Time below range (<3.0 mmol/L) | Time below range (percentage of time and amount of time with sensor glucose <3.0 mmol/L) | 18 months | 
| Time above range (>10.0 mmol/L) | Time above range (percentage of time and amount of time with sensor glucose >10.0 mmol/L) | 18 months | 
| Time above range (>13.9 mmol/L) | Time above range (percentage of time and amount of time with sensor glucose >13.9 mmol/L) | 18 months | 
| Mean sensor glucose | Mean sensor glucose derived from continuous glucose monitoring | 18 months | 
| Glycemic variability | Glycemic variability (defined as coefficient of variation and standard deviation) derived from continuous glucose monitoring | 18 months | 
| Arrhythmia leading to the implantation of a cardiac implantable electronic device | Presence of any arrhythmia leading to the implantation of a cardiac implantable electronic device | 18 months | 
| Arrhythmia leading to a medical intervention | Presence of any arrhythmia leading to a medical intervention (defined as any change in prescribed medication) | 18 months | 
| Adverse events | Presence of adverse events, including procedure related adverse events | 18 months | 
| Sudden cardiac death | Sudden cardiac death | 18 months | 
| Cardiovascular death | Cardiovascular death | 18 months | 
| All-cause mortality | All-cause mortality | 18 months |