Combining Myocardial Strain and Cardiac CT to Optimize Left Ventricular Lead Placement in CRT Treatment (CRT clinic)

Individually Tailored Cardiac Resynchronization Therapy - Combing Myocardial Strain and Cardiac CT to Optimize Left Ventricular Lead Placement in Cardiac Resynchronization Therapy

For patients with advanced heart failure, Cardiac Resynchronization Therapy (CRT) has been a major improvement. The treatment improves symptoms and prolongs life in selected patients with heart failure. However, with the current selection criteria and methods for implanting the pacemaker, only 60-70% of the patients derive significant benefit from the treatment.

New imaging techniques, including advanced ultrasound and computed tomography, in combination with new versatile multi-pole electrodes, have made an individually tailored therapy possible. Using these techniques in combination, the study will investigate the effect of individually based "optimal" placement of the pacemaker electrodes vs. standard care. The optimal LV electrode position is defined as pacing a viable segment with the latest mechanical delay, targeting a specific segment of the coronary sinus as visualised on cardiac CT. The hypothesis is that this will increase the number of positive responders from 65% to 85%.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Other: Imaging guided LV lead positioning

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 221 85
    • Skåne University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptomatic heart failure (New York Heart Association functional class II - IV) despite stabile optimal medical therapy.
• Wide QRS ≥ 120 milliseconds on standard ECG.
• LV systolic dysfunction (EF ≤ 35%).
• Written informed consent.
• Accepted for CRT-P or CRT-D treatment

Exclusion Criteria:

• Life expectancy < 12 months.
• Recent myocardial infarction (< 3 months).
• Significant valve disease
• Chronic atrial fibrillation
• Pregnancy
• Severely impaired renal function (estimated glomerular filtration rate (eGFR) < 30 ml/min)
• Unable to give written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Imaging guided LV lead positioning	Other: Imaging guided LV lead positioning; LV lead positioning guided by echocardiography (mechanical strain evaluation by speckle tracking) in combination with cardiac CT. A viable segment with the latest mechanical activation is targeted, and an appropriate "optimal" cardiac vein segment is then chosen using the CT images.
No Intervention: Standard LV lead positioning; The LV lead position is decided at the discretion of the treating physician. Cardiac CT images are available for viewing, but no echocardiography data regarding segmental myocardial strain are available.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive response to CRT treatment	The primary efficacy endpoint will evaluate the effect of echocardiography and cardiac CT guided placement of the left ventricular lead vs standard care (i.e. position of the left ventricular lead at the discretion of the treating physician). Number of patients with positive response to CRT (YES or NO). A positive response is defined as survival in combination with either a reduction in end systolic left ventricular volume ≥ 15% by echocardiography ("volume responder") and / or improvement ≥ 1 NYHA class and ≥10% improvement in 6 minute hall walk test ("clinical responder").	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to CRT (on-treatment analysis)	Evaluate the effect of optimal LV placement (post hoc analysis of both groups) versus non-optimal LV lead placement. Optimal lead placement is defined as pacing from a viable segment with the latest mechanical activation (by myocardial strain measurement). Outcome measure is the same as in the primary outcome measure.	6 months
Heart failure morbidity	Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to hospitalisation for worsening of heart failure	6 months 2 years and 5 years
Morbidity and mortality	Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to a composite endpoint of all cause mortality and hospitalisation for worsening of heart failure (2 years and 5 years).	6 months 2 years and 5 years
Mortality	Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to all cause mortality	6 months, 2 years and 5 years
Left ventricular dyssynchrony	Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to echocardiography measured changes in LV dyssynchrony	6 months
Ventricular tachycardia	Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to number of treated ventricular tachycardia episodes	6 months 2 years and 5 years
Quality of life	Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to the change in the Minnesota Living with heart failure Quality of Life questionnaire	6 months 2 years 5 years
Myocardial viability	Evaluate the concordance in viability assessment using myocardial strain evaluation (echocardiography) compared to cardiac MRI.	Peroperative
Biochemical markers of heart failure	Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to the change in blood natriuretic peptide (BNP) levels	6 months
Left ventricular systolic function	Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to the change in LV ejection fraction	6 months
Myocardial viability	Evaluate the concordance between echocardiography (strain evaluation with speckle tracking) and cardiac MRI viability images (late gadolinium enhancement).	6 months
MRI left ventricular dyssynchrony	Evaluate if MRI dyssynchroni evaluation has incremental value over echocardiography alone for predicting the effect of cardiac resynchronization therapy.	6 months
Left ventricular diastolic dimension	Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to the change in left ventricular diastolic dimension	6 months

Collaborators and Investigators

• Sponsor: Region Skane
• Collaborators: Crafoord Foundation
• Investigators: Principal Investigator: Rasmus Borgquist, MD PhD, Region Skane

Publications and helpful links

General Publications

• Borgquist R, Carlsson M, Markstad H, Werther-Evaldsson A, Ostenfeld E, Roijer A, Bakos Z. Cardiac Resynchronization Therapy Guided by Echocardiography, MRI, and CT Imaging: A Randomized Controlled Study. JACC Clin Electrophysiol. 2020 Oct;6(10):1300-1309. doi: 10.1016/j.jacep.2020.05.011. Epub 2020 Aug 12.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2011
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: August 25, 2011
• First Submitted That Met QC Criteria: August 30, 2011
• First Posted (Estimate): August 31, 2011

Study Record Updates

• Last Update Posted (Actual): March 28, 2019
• Last Update Submitted That Met QC Criteria: March 27, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Echocardiography; Cardiac resynchronization therapy; Cardiac computed tomography
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CRTCLIN01