Viability and Cardiac Resynchronization Therapy

Heart Failure Clinical Trial

Official title:

The Importance of Viability for Response to Cardiac Resynchronization Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00955539
• Other study ID #: H-B-2009-057
• Status: Recruiting
• Phase: N/A
• First received: August 7, 2009
• Last updated: October 4, 2011
• Start date: August 2009
• Est. completion date: June 2013

Study information

• Verified date: October 2011
• Source: University Hospital, Gentofte, Copenhagen
• Contact: Niels Risum, M.D.
• Phone: +45 39978473
• Email: nieris01[@]geh.regionh.dk
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: The Regional Committee on Biomedical Research EthicsDenmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Heart Failure
• Ischemic Cardiomyopathy

Intervention

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.
• 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.

Locations

Country	Name	City	State
Denmark	Gentofte University Hospital	Hellerup
Sweden	University Hospital Lund	Lund

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	Lund University Hospital, Rigshospitalet, Denmark

Countries where clinical trial is conducted

Denmark,  Sweden, 

References & Publications (4)

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. Review. — View Citation

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. Epub 2006 Feb 13. — View Citation

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. Epub 2005 Mar 7. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	Clinical: >/= 25% increase in 6-min walk test or >/= 1 reduction in NYHA-class		4 and 8 months (follow-up 2 years)	No