Non-Invasive Cardiac Output Measurement for CRT Optimization

Congestive Heart Failure Clinical Trial

— NICaS-CRT  

Official title:

The Use of Impedance-Based Non-invasive Cardiac Output Measurement (NICaS) for Optimizing Cardiac Resynchronization Therapy: a Pilot Clinical Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02126241
• Other study ID #: SHEBA-1176-14-MG-CTIL
• Status: Completed
• Phase: N/A
• First received: April 27, 2014
• Last updated: August 5, 2015
• Start date: April 2014
• Est. completion date: May 2015

Study information

• Verified date: August 2015
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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.

Exclusion Criteria:

• NYHA class IV heart failure

• Permanent or persistent atrial fibrillation

• Bi-ventricular pacing <90%

• Inability to perform the six-minute walk test

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Other:
• NICaS guided CRT optimization
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

Locations

Country	Name	City	State
Israel	Sheba Medical Center	Ramat Gan

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (5)

Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE; ESC Committee for Practice Guidelines (CPG), Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers, Kirchhof P, Blomstrom-Lundqvist C, Badano LP, Aliyev F, Bänsch D, Baumgartner H, Bsata W, Buser P, Charron P, Daubert JC, Dobreanu D, Faerestrand S, Hasdai D, Hoes AW, Le Heuzey JY, Mavrakis H, McDonagh T, Merino JL, Nawar MM, Nielsen JC, Pieske B, Poposka L, Ruschitzka F, Tendera M, Van Gelder IC, Wilson CM. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J. 2013 Aug;34(29):2281-329. doi: 10.1093/eurheartj/eht150. Epub 2013 Jun 24. — View Citation

Delnoy PP, Ritter P, Naegele H, Orazi S, Szwed H, Zupan I, Goscinska-Bis K, Anselme F, Martino M, Padeletti L. Association between frequent cardiac resynchronization therapy optimization and long-term clinical response: a post hoc analysis of the Clinical Evaluation on Advanced Resynchronization (CLEAR) pilot study. Europace. 2013 Aug;15(8):1174-81. doi: 10.1093/europace/eut034. Epub 2013 Mar 14. — View Citation

Heinroth KM, Elster M, Nuding S, Schlegel F, Christoph A, Carter J, Buerke M, Werdan K. Impedance cardiography: a useful and reliable tool in optimization of cardiac resynchronization devices. Europace. 2007 Sep;9(9):744-50. Epub 2007 May 11. — View Citation

Tanino Y, Shite J, Paredes OL, Shinke T, Ogasawara D, Sawada T, Kawamori H, Miyoshi N, Kato H, Yoshino N, Hirata K. Whole body bioimpedance monitoring for outpatient chronic heart failure follow up. Circ J. 2009 Jun;73(6):1074-9. Epub 2009 Apr 16. — View Citation

Turcott RG, Witteles RM, Wang PJ, Vagelos RH, Fowler MB, Ashley EA. Measurement precision in the optimization of cardiac resynchronization therapy. Circ Heart Fail. 2010 May;3(3):395-404. doi: 10.1161/CIRCHEARTFAILURE.109.900076. Epub 2010 Feb 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Predictors for significant cardiac output improvement	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.	Within the first year after beginning of study	No
Secondary	Acute six-minute walk test changes after NICaS optimization	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.	Within the first 24 hours after enrollment	No
Secondary	Reverse remodeling	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.	At 6 months after enrollment	No
Secondary	Hospitalization rate for heart failure	Hospitalization rate for acute heart failure during the first 6 months following NICaS guided CRT optimization	Within the first 6 months after enrollment	Yes
Secondary	Supraventricular arrhythmia occurrence	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.	At 6 months after enrollment	No
Secondary	Clinical improvement	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.	At 6 months after enrollment	No