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Non-Invasive Cardiac Output Measurement for CRT Optimization

Not Applicable
Completed
Conditions
Congestive Heart Failure
Interventions
Other: NICaS guided CRT optimization
Registration Number
NCT02126241
Lead Sponsor
Sheba Medical Center
Brief Summary

This proposal aims to evaluate the added clinical and echocardiographic benefit of using the non-invasive impedance-based cardiac output measurement system (NICaS) for optimizing atrio-ventricular and inter-ventricular delays in chronic (more than 6 months) CRT recipients.

Detailed Description

1. Introduction

Cardiac resynchronization therapy (CRT) is an efficient treatment in heart failure (HF) patients with left ventricular (LV) systolic dysfunction and wide QRS. It is associated with improved exercise capacity, quality of life and left ventricular ejection fraction, as well as reverse remodeling, mitral regurgitation reduction, and mortality reduction.

Predicting response to CRT is important as 30% of patients have no or minimal clinical improvement following CRT. Several parameters have been shown to influence response following implantation. Some relate to patients' characteristics including underlying heart disease, comorbidities and arrhythmias, type and severity of conduction disorder, presence and degree of dyssynchrony, presence and extent of scar tissue and functional myocardial reserve. Others are associated with technical aspects, including electrical and anatomical positioning of LV lead, programming mode and percentage of effective bi-ventricular pacing.

Optimization of the atrio-ventricular (AV) delay and inter-ventricular (VV) delays can be used for maximizing CRT benefit, but is not routinely recommended by current guidelines. Standard optimization is performed under echocardiography guidance - a time and resource consuming method. Other non-invasive methods, such as impedance cardiography, can be used for AV delay optimization.

2. Rationale for CRT optimization using NICaS

The non-invasive cardiac system (NICaS) is a whole-body bioimpedance measurement method allowing real-time cardiac output (CO) assessment. It has been FDA approved for assisting in the diagnosis, monitoring and care management of patients with congestive heart failure as well as for cardiac pacemaker optimization. Clinical trials have shown its utility for the follow-up of outpatient monitoring chronic heart failure, for monitoring patients with heart failure and pulmonary hypertension.

NICaS is sensitive enough for detecting real-time small changes in CO. Based on NICaS measured CO changes following AV and VV delays modifications, small series support its use for CRT optimization in a clinical setting, suggesting it may be associated with a reduction in non-responder rate.

3. Hypothesis

We hypothesize that the use of NICaS for optimization of AV and VV delays in chronic (more than 6 months) CRT recipients may result in an added clinical and echocardiographic benefit.

4. Specific Aims

1. Identify the CRT recipients who are prone to benefit following CRT optimization, by finding the predictors (clinical, ECG, echocardiographic, hemodynamic) for significant cardiac output improvement after NICaS guided CRT optimization

2. Correlate the degree of cardiac output improvement (as measured by NICaS) after NICaS guided CRT optimization, with clinical and echocardiographic changes at 6 months

5. Timeline:

I. At Inclusion

I.A. Baseline assessment. Patients included in the study will benefit from the following at baseline assessment, performed in an outpatient setting:

1. Clinical evaluation:

1. history;

2. NYHA class; six-minute walk test (6MWT); Minnesota Living with Heart Failure questionnaire for the quality of life (QoL);

3. status following CRT (responder/non-responder);

4. physical evaluation;

5. current medication

2. ECG

3. Device interrogation

4. Transthoracic echocardiography (including dyssynchrony parameters)

I.B. NICaS protocol for optimal AV and VV delays assessment. After baseline assessment is completed, patients will benefit from NICaS hemodynamic assessment and CRT programming according to NICaS guided optimal AV and VV delays. (for NICaS protocol for optimal AV and VV delays measurements - see Interventions)

I.C. After NICaS guided CRT programming, patients will perform a 6MWT

II. At 6 months follow-up. At 6 months, patients will benefit from the following evaluations:

1. Clinical: NYHA class, 6MWT, Minnesota Living with Heart Failure questionnaire for the quality of life, current medication

2. ECG

3. Device interrogation

4. Transthoracic echocardiography

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
42
Inclusion Criteria
  • Patients implanted with a CRT device at least 6 months before, in concordance with AHA/ACC or ESC/EHRA Guidelines (Class I or II) for CRT implantation
  • NYHA class I - III heart failure
  • Stable sinus rhythm
  • Bi-ventricular pacing ≥ 90%
  • Patient provides informed consent.
Read More
Exclusion Criteria
  • NYHA class IV heart failure
  • Permanent or persistent atrial fibrillation
  • Bi-ventricular pacing <90%
  • Inability to perform the six-minute walk test
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
NICaS guided CRT optimizationNICaS guided CRT optimizationFor each subject, we will determine a set of AV and VV delays values, for which the NICaS measured CO will be maximum. In each patient, the CRT device will then be programmed according to these values.
Primary Outcome Measures
NameTimeMethod
Predictors for significant cardiac output improvementWithin the first year after beginning of study

Using logistic regression, we will look for predictors (clinical, ECG, echocardiographic, hemodynamic) of significant (at least 20%) acute cardiac output improvement (as assessed by NICaS), after NICaS guided AV and VV delays optimization.

Secondary Outcome Measures
NameTimeMethod
Clinical improvementAt 6 months after enrollment

Clinical improvement at 6 months after CRT optimization will be assessed using a composite score combining NYHA class, QoL and the 6MWT.

Each will be classified as improved (+1), stable (0) or worsened (-1) and the three components will be summed. The patient will be considered improved if he will have had ≥1 class reduction in his NYHA class, worsened if he will have had ≥1 class increase and unchanged if he will have had no change in his baseline NYHA class. Similar definitions will be used for absolute variation (improvement or deterioration) of 10 points in QoL, or relative 10%change in six-minute walk distance.

A clinical improvement will be considered in the presence of a summed score ≥+1 without death during the first 6 months of follow-up after CRT optimization.

Acute six-minute walk test changes after NICaS optimizationWithin the first 24 hours after enrollment

After NICaS guided AV and VV delays optimization, each patient will perform a six-minute walk test, which will be compared to the baseline (before NICaS optimization) six-minute walk test. A 10% change will be considered significant.

Reverse remodelingAt 6 months after enrollment

Each patient will undergo routinely a 6-month echocardiography which will be compared to the baseline (inclusion day) echocardiography. A relative reduction of 10% of the left ventricular end-systolic volume will be considered as positive reverse remodeling.

Hospitalization rate for heart failureWithin the first 6 months after enrollment

Hospitalization rate for acute heart failure during the first 6 months following NICaS guided CRT optimization

Supraventricular arrhythmia occurrenceAt 6 months after enrollment

CRT device measurement of the total time spent in auto-mode switch during the first 6 months following NICaS guided CRT optimization, and comparison to the 6 months prior to the optimization.

Trial Locations

Locations (1)

Sheba Medical Center

🇮🇱

Ramat Gan, Israel

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