Post-Extrasystolic Potentiation as a Predictor of Ventricular Arrhythmias (A PRIORY)

Background: Patients at increased risk for sudden cardiac death (SCD) may receive an implantable cardioverter defibrillator (ICD). The primary criterion for a primary prevention ICD implantation is a left ventricular ejection fraction (LVEF) below 35%, but refinement of ICD criteria is important since only a small proportion of ICD patients receives appropriate device therapy (ATP or a shock) during follow-up. Post-extrasystolic potentiation (PESP) may be a new risk marker for SCD. PESP is defined as a temporary increase in contractility that follows an extrasystolic beat (ESB) and is associated with myocardial calcium handling. In heart failure, changes in calcium homeostasis may lead to afterdepolarisations and thus predispose for SCD. PESP can be measured indirectly and non-invasively as post-extrasystolic blood pressure potentiation (PESP-BP). Abnormal PESP-BP was previously found to be an independent predictor of increased mortality in post-myocardial infarction patients with a reduced LVEF. However, it is unknown if this increased mortality in heart failure patients with abnormal PESP-BP is caused by an increased risk of SCD.

Hypothesis: The investigators hypothesize that PESP-BP might be a new predictor of the occurrence of SCD, and can be used to enhance patient selection for primary prevention ICD therapy.

Design: During scheduled device replacement ESB with various extrasystolic and post-extrasystolic coupling intervals will be evoked by electrical stimulation via the right atrial and ventricular device leads of the patient. Throughout the stimulation study blood pressure will be measured non-invasively a continuous electrocardiogram will be recorded. Either before or after the procedure, patients will undergo a 30-minutes assessment of spontaneous ESB, again with blood pressure and ECG recordings.

Study population: 30 patients who are scheduled for device replacement or reposition, are eligible for this study; (1) 10 ICD patients who previously received appropriate device therapy (ADT); (2) 10 ICD patients who are free from ADT and (3) 10 dual-chamber pacemaker patients (control group).

Outcomes: (1) Evoked PESP-BP (i.e. blood pressure differences between baseline, ESB and post-ESB); (2) Spontaneous PESP-BP (i.e. blood pressure differences between baseline, ESB and post-ESB); (3) Timing parameters (in ms): the basic cycle length interval; Extra-systolic interval (ESI); Post-extrasystolic interval (PESI).

Study Overview

• Status: Unknown
• Conditions: Ventricular Tachycardia; Post-extrasystolic Potentiation (PESP)
• Intervention / Treatment: Device: Cardiac stimulation through the device leads

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081HV
    • Recruiting
    • VU University Medical Center
    • Contact: Anne-Lotte van der Lingen, MD; Phone Number: +31204443272; Email: a.vanderlingen@vumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

30 patients who are scheduled for device replacement or reposition, are eligible for this study; (1) 10 ICD patients who previously received appropriate device therapy (ATP/shock); (2) 10 ICD patients who are free from ADT and (3) 10 dual-chamber pacemaker patients (control group)

Description

Inclusion Criteria:

• Implanted with a dual-chamber device
• For ICD patients: a LVEF ≤35%, measured recently
• For Pacemaker patients: a LVEF > 50% measured both recently
• A device follow-up of at least one year must be available
• Optimal (stable) medical therapy
• Sinus rhythm

Exclusion Criteria:

• Age <18 or incapacitated adult
• Unknown left ventricular function prior to device implantation
• Patients unwilling to participate
• Documented atrial fibrillation
• Second or third degree atrioventricular (AV) conduction disorders;
• Patients with a cardiac resynchronization therapy (CRT-D) or one-chamber device
• Hypertrophic cardiomyopathy
• Conditions with insufficient blood flow to the fingers, e.g. M. Raynaud or conditions with extreme vasoconstriction

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ICD patients with ATP/shock; 10 primary prevention 2-chamber ICD patients (LVEF <35 percent) who received appropriate ICD therapy during follow-up.	Device: Cardiac stimulation through the device leads; During scheduled device replacement extra-systolic beats with various extrasystolic and post-extrasystolic coupling intervals will be evoked by electrical stimulation via the right atrial and ventricular device leads of the patient. Throughout the stimulation study blood pressure will be measured non-invasively using a finger arterial blood pressure photoplethysmographic device and a continuous electrocardiogram will be recorded.
ICD patients without ATP/Shock; 10 primary prevention 2-chamber ICD patients (LVEF <35 percent) who were free from appropriate ICD therapy during follow-up.	Device: Cardiac stimulation through the device leads; During scheduled device replacement extra-systolic beats with various extrasystolic and post-extrasystolic coupling intervals will be evoked by electrical stimulation via the right atrial and ventricular device leads of the patient. Throughout the stimulation study blood pressure will be measured non-invasively using a finger arterial blood pressure photoplethysmographic device and a continuous electrocardiogram will be recorded.
Pacemaker-patients; 10 2-chamber pacemaker-patients (LVEF >50%).	Device: Cardiac stimulation through the device leads; During scheduled device replacement extra-systolic beats with various extrasystolic and post-extrasystolic coupling intervals will be evoked by electrical stimulation via the right atrial and ventricular device leads of the patient. Throughout the stimulation study blood pressure will be measured non-invasively using a finger arterial blood pressure photoplethysmographic device and a continuous electrocardiogram will be recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evoked PESP-BP	blood pressure differences between baseline, extrasystolic beat (ESB) and post-ESB	Measured during stimulation protocol
Spontaneous PESP-BP	blood pressure differences between baseline, extrasystolic beat (ESB) and post-ESB	Measured in rest, without cardiac stimulation with spontaneous ESB

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Investigators: Principal Investigator: Cornelis P. Allaart, MD, PhD, Amsterdam Umc, Location Vumc

Publications and helpful links

General Publications

• Steger A, Sinnecker D, Barthel P, Muller A, Gebhardt J, Schmidt G. Post-extrasystolic Blood Pressure Potentiation as a Risk Predictor in Cardiac Patients. Arrhythm Electrophysiol Rev. 2016 May;5(1):27-30. doi: 10.15420/aer.2016.14.2.
• Sinnecker D, Dirschinger RJ, Barthel P, Muller A, Morley-Davies A, Hapfelmeier A, Dommasch M, Huster KM, Hasenfuss G, Laugwitz KL, Malik M, Schmidt G. Postextrasystolic blood pressure potentiation predicts poor outcome of cardiac patients. J Am Heart Assoc. 2014 Jun 3;3(3):e000857. doi: 10.1161/JAHA.114.000857.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): March 1, 2020

Study Registration Dates

• First Submitted: August 12, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): November 20, 2018
• Last Update Submitted That Met QC Criteria: November 19, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Sudden Cardiac Death; Implantable cardioverter defibrillator; Post-extrasystolic Potentiation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Tachycardia; Tachycardia, Ventricular
• Other Study ID Numbers: 2018.246

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No