Clinical trial NCT01076660: Left Ventricular Structural Predictors of Sudden Cardiac Death
Official title: Left Ventricular Structural Predictors of Sudden Cardiac Death [Substudy of: Functional Energetics and Imaging for Phenotypic Characterization of Patients at Risk for Sudden Cardiac Death, See Also NCT000181233]
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ischemic Cardiomyopathy
Nonischemic Cardiomyopathy
Keywords: Ischemic cardiomyopathy
Nonischemic cardiomyopathy
Implantable cardioverter defibrillator
Sudden Cardiac Death
Ventricular tachycardia
Ventricular fibrillation
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Donald W. Reynolds Foundation
name: Christiana Care Health Services
First posted: 2010-02-26
Enrollment: 400
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with LV ejection fraction (LVEF) ≤35% of ischemic or nonischemic etiology (as measured by a clinical echocardiogram, ventriculogram, or radionuclide study) referred clinically for ICD insertion for primary prevention purposes (i.e. no prior history of sustained ventricular arrhythmias)

Brief summary: Sudden cardiac death (SCD) poses a significant health care challenge with high annual incidence and low survival rates. Implantable cardioverter defibrillators (ICDs) prevent SCD in patients with poor heart function. However, the critical survival benefit afforded by the devices is accompanied by short and long-term complications and a high economic burden. Moreover, in using current practice guidelines of reduced heart function, specifically left ventricular ejection fraction (LVEF)≤35%, as the main determining factor for patient selection, only a minority of patients actually benefit from ICD therapy (\<25% in 5 years). There is an essential need for more robust diagnostic approaches to SCD risk stratification.

This project examines the hypothesis that structural abnormalities of the heart itself, above and beyond global LV dysfunction, are important predictors of SCD risk since they indicate the presence of the abnormal tissue substrate required for the abnormal electrical circuits and heart rhythms that actually lead to SCD. Information about the heart's structure will be obtained from cardiac magnetic resonance imaging and used in combination with a number of other clinical risk factors to see if certain characteristics can better predict patients at risk for SCD.

Detailed description: Sudden cardiac death (SCD) poses a significant health care challenge with high annual incidence and low survival rates. Implantable cardioverter defibrillators (ICDs) prevent SCD in patients with left ventricular (LV) systolic dysfunction. However, the critical survival benefit afforded by the devices is accompanied by short and long-term complications and a high economic burden. Moreover, in using current practice guidelines of LV ejection fraction (LVEF)≤35% as the main determining factor for patient selection, only a minority of patients actually benefit from ICD therapy (\<25% in 5 years). There is an essential need for more robust diagnostic approaches to SCD risk stratification.

This project examines the hypothesis that LV structural abnormalities above and beyond global LV dysfunction are important predictors of SCD risk since they indicate the presence of abnormal pathophysiologic substrate required for the ventricular arrhythmogenicity leading to SCD. This premise is supported by pre-clinical models and limited patient cohort studies examining the contribution of individual LV structural indices. However, there has been no prospective study of primary prevention ICD candidates in sufficiently large numbers to investigate the incremental value of a comprehensive assessment of LV structure on SCD risk over and above that of LVEF and readily available demographic and clinical variables.

LV structure can be quantified in detail using cardiac magnetic resonance imaging with late gadolinium enhancement (CMR-LGE). Specifically, accurate assessment of global LV function, volumes, mass, geometry, and infarct/scar characteristics are feasible and obtainable clinically in a single examination. We aim to examine whether or not any of these CMR indices or combination of indices are better able to discriminate between patients with high versus low susceptibility to SCD within the broader population of reduced LVEF patients. If the results of these studies demonstrate that LV structure is an important prognostic risk factor, it may be then be possible to more specifically focus ICD therapy to those who are most likely to benefit and avoid unnecessary device implantations.

Eligibility criteria: Inclusion Criteria:

* LVEF≤35%, referred clinically for ICD insertion for primary prevention purposes (i.e. no prior history of sustained ventricular arrhythmias)
* Between the ages of 21 and 80 years old
* Permission of the patient's clinical attending physician

Exclusion Criteria:

* Patients who refuse or are unable to give consent.
* Individuals with contraindications to MRI (i.e. implanted metallic objects such as pre-existing cardiac pacemakers, cerebral clips or indwelling metallic projectiles)
* Minors.
* Pregnant women.
* NYHA Class IV heart failure.
* Chronic renal insufficiency with creatinine clearance\<60 ml/min; acute renal insufficiency of any severity
* Claustrophobia
* Prior adverse reaction to gadolinium-based contrast

Primary outcomes:
measure: Composite SCD outcomes
timeFrame: Every 6 months for 5 years
Secondary outcomes:
measure: Composite cardiac outcomes
timeFrame: Every 6 months for 5 years
Other outcomes:
Locations:
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Baltimore
country: United States
facility: Johns Hopkins Medical Institutions
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Katherine Wu, MD
role: PRINCIPAL_INVESTIGATOR
References:
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