Viability and Cardiac Resynchronization Therapy

The Importance of Viability for Response to Cardiac Resynchronization Therapy

30% of heart failure patients that receive a device for cardiac resynchronization therapy fail to show clinical improvement. The reason for lack of response is still unclear but factors such as scar tissue in the heart musculature, inadequate lead placement, device-settings and the degree of dyssynchrony before implant seems to be important. In this study, these factors are further investigated.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Ischemic Cardiomyopathy
• Intervention / Treatment: Device: AV-optimization followed by AV- and VV-optimization; Device: AV- and VV-optimization followed by AV-optimization only.

Detailed Description

Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure, depressed left ventricular function and a wide QRS-complex. Large clinical trials have demonstrated unequivocal improvements in functional status, morbidity and mortality. However, 30 % of heart failure patients treated with a CRT-device do not benefit clinically. Several factors have been suggested to be important for the response to CRT such as mechanical dyssynchrony, presence of scar tissue in the myocardium, and device-optimization (among others). It is the purpose of this study to investigate the importance of these factors.

100 patients with ischemic cardiomyopathy, eligible to CRT according to current guidelines, will be included. Patients are randomised to two arms. One group will have atrioventricular (AV)-optimization after implantation, the other AV -and interventricular (VV)-optimization. After 4 months patients are crossed-over to the other arm. Preimplantation patients are MR-scanned and low-dose dobutamine stress-echocardiography is performed. Furthermore patients will be examined by echocardiography and evaluation of clinical status

1. Mechanical dyssynchrony can predict response to CRT. b. Measures of mechanical dyssynchrony is related to myocardial viability and conduction.
2. Individual optimization based on conduction times will increase benefit to CRT. b. The effect of adding VV-optimization is related to myocardial viability.
3. > 30 % of non-viable tissue globally in the myocardium is predictive of lack of CRT- response. b. Non-viable tissue located in the area of the left ventricular lead is predictive of non-response.

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

Contacts and Locations

• Study Contact: Name: Niels Risum, M.D.; Phone Number: +45 39978473; Email: nieris01@geh.regionh.dk
• Study Contact Backup: Name: Thomas Fritz Hansen, M.D.; Phone Number: +45 39773977; Email: THHAN@geh.regionh.dk

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Recruiting
    • Gentofte University Hospital
    • Contact: Niels Risum, M.D.; Phone Number: +45 39978473; Email: nieris01@geh.regionh.dk
    • Contact: Thomas Fritz Hansen, M.D.; Phone Number: +45 39773977; Email: THHAN@geh.regionh.dk
    • Principal Investigator: Niels Risum, M.D.
• Sweden
  • Lund, Sweden, 221 85
    • Recruiting
    • University Hospital Lund
    • Contact: Rasmus Borgquist, MD, PhD; Phone Number: +46 70-4057350; Email: rasmus.borgquist@med.lu.se
    • Principal Investigator: Rasmus Borgquist, MD, PhD

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:

• LVEF</= 35%, QRS-duration>/= 120 ms, NYHA-class II- IV.
• Ischemic heart disease (> 50% stenosis in 1 or more major epicardial coronary artery or prior PCI or CABG.)
• Optimal treatment ( beta-blocker, ACE-1 or ARB and spironolactone)

Exclusion Criteria:

• Pregnancy
• Unstable angina pectoris
• Chronical atrial fibrillation
• Severe valvular disease
• Dementia or mental retardation
• Severe claustrophobia
• Acute myocardial infarction < 3 months
• Severe health condition threatening short-term survival
• Severe kidney insufficiency, GFR < 35 ml/min/1.73 m2
• Metal implants contraindicative of magnetic resonance scan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CRT group 1	Device: AV-optimization followed by AV- and VV-optimization; Patients are AV-optimized the first 4 months,then AV- and VV-optimized the next 4 months.
Active Comparator: CRT group 2	Device: AV- and VV-optimization followed by AV-optimization only.; Patients are AV- and VV-optimized the first 4 months,then AV-optimized the next 4 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Responders:Echocardiographic:>/= 10% increase in Left ventricular ejection fraction (LVEF) or >/= 15 % reduction in left ventricular end-systolic volume (LVESV)	4 and 8 months, ( follow up- 2 years)

Secondary Outcome Measures

Outcome Measure	Time Frame
LVESV, LVEDV, Cardiac output (CO), Minnesota Living with Heart Failure Questionnaire (MLHFQ) ProBNP Others: t-wave modulation all-cause mortality, cardiac death, hospitalization	4 and 8 months (follow-up after 2 years)
Clinical: >/= 25% increase in 6-min walk test or >/= 1 reduction in NYHA-class	4 and 8 months (follow-up 2 years)

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: Rigshospitalet, Denmark; Lund University Hospital
• Investigators: Principal Investigator: Niels Risum, M.D., University Hospital Gentofte, Department of Cardiology; Study Chair: Thomas Fritz Hansen, M.D., University Hospital Gentofte, Department of Cardiology; Study Chair: Peter Søgaard, M.D., DMSc., Gentofte University Hospital, department of cardiology; Study Chair: Rasmus Borgquist, MD, PhD, University Hospital Lund; Study Chair: Niels E Bruun, MD, DMSc, Gentofte University Hospital, department of cardiology

Publications and helpful links

General Publications

• Bax JJ, Abraham T, Barold SS, Breithardt OA, Fung JW, Garrigue S, Gorcsan J 3rd, Hayes DL, Kass DA, Knuuti J, Leclercq C, Linde C, Mark DB, Monaghan MJ, Nihoyannopoulos P, Schalij MJ, Stellbrink C, Yu CM. Cardiac resynchronization therapy: Part 1--issues before device implantation. J Am Coll Cardiol. 2005 Dec 20;46(12):2153-67. doi: 10.1016/j.jacc.2005.09.019.
• Sogaard P, Egeblad H, Pedersen AK, Kim WY, Kristensen BO, Hansen PS, Mortensen PT. Sequential versus simultaneous biventricular resynchronization for severe heart failure: evaluation by tissue Doppler imaging. Circulation. 2002 Oct 15;106(16):2078-84. doi: 10.1161/01.cir.0000034512.90874.8e.
• Bleeker GB, Kaandorp TA, Lamb HJ, Boersma E, Steendijk P, de Roos A, van der Wall EE, Schalij MJ, Bax JJ. Effect of posterolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronization therapy. Circulation. 2006 Feb 21;113(7):969-76. doi: 10.1161/CIRCULATIONAHA.105.543678. Epub 2006 Feb 13.
• Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49. doi: 10.1056/NEJMoa050496. Epub 2005 Mar 7.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): June 1, 2013

Study Registration Dates

• First Submitted: August 7, 2009
• First Submitted That Met QC Criteria: August 7, 2009
• First Posted (Estimate): August 10, 2009

Study Record Updates

• Last Update Posted (Estimate): October 6, 2011
• Last Update Submitted That Met QC Criteria: October 4, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiac resynchronization therapy; Optimization; Viability; Mechanical dyssynchrony
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Cardiomyopathies
• Other Study ID Numbers: H-B-2009-057

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No