Clinical trial NCT04409119: Direct HIS/LBB Pacing as an Alternative to Biventricular Pacing in Patients With HFrEF and a Typical LBBB.
Official title: Direct HIS/LBB Pacing as an Alternative to Biventricular Pacing in Patients With Symptomatic Heart Failure Despite Optimal Medical Treatment and an ECG With a Typical Left Bundle Branch Block Pattern.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Left Bundle-Branch Block
Keywords: left bundle branch block
HIS-pacing
LBB-pacing
left bundle branch pacing
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Imperial College Healthcare NHS Trust
First posted: 2020-06-01
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will investigate the feasibility of using direct HIS pacing or left bundle branch pacing (LBB pacing) as an alternative to biventricular pacing in patients with symptomatic heart failure and an ECG with a typical left bundle branch block pattern.

Detailed description: Biventricular pacing has for more than a decade been standard of care for patients with HFrEF, LVEF \< 35%, NYHA II-IV despite optimal medical treatment and an ECG with left bundle branch block (LBBB). However, it is not always ideal because of several drawbacks such as phrenic nerve capture, inability to reach late activated areas and many more. Direct HIS pacing can in many cases capture the left bundle and provide normal electrical activation of the left ventricle but sometimes with high pacing thresholds. Recently direct left bundle branch pacing has shown promise with synchronous activation of the left ventricle at low pacing thresholds.

In the present study we randomize 150 patients in two centres to either conventional CRT (50 patients) or HIS/LBB pacing (100 patients). In the HIS/LBB arm, direct HIS-pacing is attempted first but if its not possible or the pacing threshold for capturing the left bundle branch is \> 2.5 V at 1 ms we switch to placing a LBB-lead.

Power calculation for non-inferiority: With the 50 patients in the first His Alternative study (25 Biv-CRT og 25 His-CRT) we observed a fall in systolic volumes of 34% and 46% with a standard deviation of 13-16%. Using these numbers it would take at least 108 patients to be 90% sure that the lower limit of a one-sided 97.5% confidence interval (equal to a 95% two-sided confidence interval) would be over the non-inferiority limit of -10%.

Eligibility criteria: Inclusion Criteria:

* Patients over 18 years of age, ischemic or non-ischemic cardiomyopathy with LVEF ≤ 35% assessed by echocardiography, NYHA class II-IV heart failure symptoms despite optimal medical treatment and

  * Either planned new implantation of a biventricular pacing system (CRT-P or CRT-D), where the ECG is with sinus rhythm and a typical left bundle branch block (see definition below)
  * Or planned upgrade of an existing pacemaker or ICD to a biventricular pacing system (CRT-P or CRT-D), where the ECG is with sinus rhythm and a typical left bundle branch block or there has been\> 90% right ventricular pacing from an existing pacemaker for at least 2 months prior to enrollment
* Signed informed consent

Typical left bundle branch block:

QRS width \> 130 msec for women and \> 140 msec for men QS or rS pattern in leads V1 and V2, and mid-QRS plateau phase with or without extras in at least 2 of leads V1, V2, V5, V6, I, and aVL

Exclusion Criteria:

* Existing biventricular pacing system
* Permanent atrial fibrillation
* Severe renal failure with eGFR \< 30 ml/min
* AMI or CABG within the last three months
* The patient does not want to participate

Primary outcomes:
measure: Change in Left ventricular end-systolic volume
timeFrame: 6 months
measure: Success rate of implanting a HIS-bundle lead with capture of the left bundle branch or a LBB-lead with narrowing of QRS
timeFrame: 6 months
Secondary outcomes:
measure: Change in LVEF and left ventricular chamber dimensions
timeFrame: 6 months
measure: Change in 6-min hall-walk test
timeFrame: 6 months
measure: Change in NYHA class
timeFrame: 6 months
measure: Change in Minnesota Living with Heart Failure score
timeFrame: 6 months
measure: Shortening of QRS duration
timeFrame: 6 months
measure: Change in NT-pro BNP value
timeFrame: 6 months
measure: Complications
timeFrame: 6 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: Hovedstaden
Study officials:
affiliation: Rigshospitalet, Denmark
name: Michael Vinther, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: