Non-Invasive Cardiac Output Measurement for CRT Optimization
Condition: Congestive Heart Failure
MeSH terms: Heart Failure
Study type: Interventional

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
    

Intervention name(s): NICaS guided CRT optimization
Intervention type(s): Other
Intervention description(s): Baseline CO measurement by NICaS
AV delay optimization:
AV delay will be changed (increase and decrease) by 30 ms steps , and for each new AV value, the CO will be real-time measured by NICaS
The AV delay yielding the maximal CO, will be considered the optimal AV delay
The device will be programmed using the optimal AV delay
VV delay optimization:
After Step 2, the baseline VV delay will be changed (increase and decrease; meaning that we will be pacing alternatively the LV before the RV, then the RV before the LV), by 30 ms steps, and for each new VV value, the CO will be real-time measured by NICaS
The VV delay yielding the maximal CO, will be considered the optimal VV delay
The device will be programmed using the optimal VV delay
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Heart Failure; Cardiac Resyncronization Therapy; Optimization; Non-invasive cardiac system; Impedance measured cardiac output