Clinical trial NCT01378572: Electrophysiologic and Morphologic Assessment of the Substrate to Guide Implantation of Defibrillators in Dilated Cardiomyopathy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Dilated Cardiomyopathy
Primary Prevention of Sudden Cardiac Death
Implantable Cardioverter Defibrillator
Keywords: ICD
sudden cardiac death
mapping
Lead sponsor: Catholic University of the Sacred Heart
Sponsor class: OTHER
Collaborators: name: Texas Cardiac Arrhythmia Research Foundation
name: Cardiac Arrhythmia Research Center, Centro Cardiologico Monzino, Milan, Italy
name: Policlinico Casilino ASL RMB, Rome, Italy
name: Dell'Angelo Hospital, Mestre-Venice, Italy
First posted: 2011-06-22
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with dilated cardiomyopathy (NYHA II-III heart failure, left ventricular ejection fraction \<=35%) undergoing prophylactic ICD implantation.

Brief summary: With the present study the investigators intend to identify the morphologic and electrophysiologic substrate markers of increased arrhythmic risk in patients with dilated cardiomyopathy undergoing implantation of a defibrillator for the primary prevention of sudden cardiac death. Moreover, the investigators also aim to identify if there is any electrophysiological substrate modification at the time of the first arrhythmic event in these patients. To this aim, the investigators will prospectively correlate electroanatomic mapping and cardiac magnetic resonance findings with arrhythmic events, in order to identify substrate markers of increased arrhythmic risk in patients with dilated cardiomyopathy, who are therefore more likely to benefit from a defibrillator implantation. Furthermore, electroanatomic mapping will be repeated at the time of the first arrhythmic event and compared with that at baseline, in order to evaluate any electrophysiological substrate changes.

Detailed description: A correct identification of patients at high risk of sudden cardiac death is crucial for a rational clinical management, since the demonstrated effectiveness of implantable cardioverter-defibrillators on the reduction of sudden cardiac death. Basing on the results of multiple clinical trials, left ventricular systolic function, measured as ejection fraction, is currently the only recommended tool to identify patients at higher risk of sudden death that would benefit from a prophylactic defibrillator. However, the systematic implementation of current recommendations results in a substantial number of inappropriate defibrillator implantations, while failing to prevent the majority of sudden deaths occurring in the general population. Unfortunately, at present time we have no other way to identify patients at higher risk of sudden cardiac death, since other proposed risk markers have not been consistently demonstrated of incremental value. Recent data suggest that several substrate markers, either assessed morphologically with magnetic resonance imaging, or electrophysiologically with invasive mapping procedures, may be helpful to identify subgroup of patients at higher arrhythmic risk. However, previous studies have been largely conducted on few patients, most were retrospective or with short follow-up.

We will submit patients with dilated cardiomyopathy undergoing implant of an implantable cardioverter defibrillator to a morphologic and electrophysiologic substrate evaluation including cardiac magnetic resonance with gadolinium contrast-enhancement study, and electroanatomic mapping with bipolar electrogram voltage and morphological analysis. The electroanatomic mapping and cardiac magnetic resonance will be repeated at the time of the first arrhythmic event.

We expect to define the role of anatomical and electrophysiological substrate abnormalities in determining malignant ventricular arrhythmias in patients with dilated cardiomyopathy, thus allowing a better risk stratification and prevention of sudden death.

Eligibility criteria: Inclusion Criteria:

1. Males and females ≥18 year-old with full capacity.
2. A New York Heart Association (NYHA) class II or III chronic, stable congestive heart failure (CHF).
3. A left ventricular ejection fraction (LVEF) of no more than 35 percent.

Exclusion Criteria:

1. Age \<18 years or diminished capacity.
2. Patients with LVEF ≥ 35% or asymptomatic left ventricular dysfunction.
3. Patients with NYHA class IV CHF.
4. Patients with history of ventricular arrhythmias causing pre-syncope or syncope, cardiac arrest or a spontaneous episode of sustained ventricular tachycardia (VT) (≥30 seconds at rates of \>100 bpm), unless these occurred within 48 hours of a myocardial infarction.
5. Females who are pregnant or have childbearing potential and are not using reliable methods of contraception.
6. Patients with history of restrictive, infiltrative, or hypertrophic cardiomyopathy; arrhythmogenic cardiomyopathy; constrictive pericarditis; congenital heart disease; surgically correctable valvular disease; and/or inoperable obstructive valvular disease.
7. Patients with reversible nonischemic cardiomyopathy such as acute viral myocarditis, alcohol-induced cardiomyopathy, peripartum cardiomyopathy, Takotsubo cardiomyopathy.
8. Patients with mechanical or biologic prosthetic cardiac valves.
9. Patients with history of a major psychiatric disorder, active alcohol/drug abuse, or noncompliance.
10. Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past 90 days prior to enrollment.
11. Myocardial infarction within the past 90 days prior to enrollment.
12. Angiographic evidence of coronary disease sufficient to be a candidate for coronary revascularization and likely to undergo coronary artery bypass graft surgery and/or percutaneous coronary intervention and likely to undergo such a procedure in the foreseeable future.
13. Presence of any disease, other than the patient's cardiac disease, associated with a reduced likelihood of survival for the duration of the study, including but not limited to cancer, uremia (blood urea nitrogen \>70 mg/dl or creatinine \>3.0 mg/dl), respiratory failure, hepatic failure, etc.
14. Contraindication to cardiac magnetic resonance evaluation

Primary outcomes:
measure: Arrhythmic Event
timeFrame: 2 years
measure: Change in Arrhythmogenic Substrate
timeFrame: 2 years
Secondary outcomes:
measure: Heart failure events
timeFrame: 2 years
measure: Death
timeFrame: 2 years
Other outcomes:
Locations:
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Institute, St. David's Medical Center
state: Texas
city: Milan
country: Italy
facility: Centro Cardiologico Monzino
city: Rome
country: Italy
facility: Policlinico "A. Gemelli"
Study officials:
References: