Clinical Trial: Prolonged Monitoring to Detect Ventricular Arrhythmias in Presymptomatic Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Patients

Study Status: Terminated
Recruit Status: Terminated
Study Type: Observational

Official Title: Prolonged Monitoring to Detect Ventricular Arrhythmias in Presymptomatic ARVC Patients

Brief Summary:

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited condition characterized by life threatening heart racing, presenting with palpitations, cardiac arrest (collapse requiring an ambulance) or sudden death. The disease affects the right ventricle, the part of the heart that pumps blood to the lungs. ARVC is diagnosed with a wide range of tests that focus on the pumping function and the electrical signals from the right ventricle. These factors are summarized in a score that forms the ARVC Task Force Criteria. Genetic testing has identified 5 different genes that lead to ARVC, which are detected in about 60% of patients with ARVC. This allows doctors to test family members of the patient with ARVC to determine if they are at risk of developing the condition. Currently, family members undergo testing that includes imaging and electrical tests such as a 24-hour monitor to determine if they have evidence of ARVC. With increasing frequency, family members are found to have the gene that may lead to ARVC, but little or no evidence that their hearts are affected. This may be because the family member is too young to develop the condition, or that other factors that we do not understand have protected them from developing it.

The PREPARE study will study 100 patients that carry a gene that can lead to ARVC, but do not have anything more than minor evidence that the condition is present. These patients will not have heart racing on their initial 24-hour monitor. These patients will undergo long term monitoring with an implanted heart monitor that is inserted with a minor surgical procedure, which will detect abnormal heart rhythms that may provide a clue that heart racing from ARVC is present that is not detected with a 24-hour monitor that is performed on an annual basis (St. Jude Confirm implantable loop recorder). These patients will be enrolled in 10 adult an

Detailed Summary:

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a familial condition characterized by onset of life threatening ventricular arrhythmias in early adulthood, presenting with ventricular tachycardia, cardiac arrest or sudden death. The disease is diagnosed with tests that focus on imaging the right ventricle and assessing for ambient arrhythmia or abnormal electrical substrate. These factors are collated into a score that forms the ARVC Task Force Criteria, known to be specific but not sensitive. These criteria have been revised in 2010, introducing a broader and more quantitative approach to diagnosis including genetic testing results, intended to enhance sensitivity without reducing specificity. They account for findings from genetic testing, confounded in part by the unknown significance of a positive genetic test in the absence of a phenotype in a disease with variable penetrance and expressivity. Genetic testing identifies the underlying mutation in ≈60% of clearly affected patients. Recent access to genetic testing has demonstrated that family members of an affected individual often harbor the culprit mutation, with little evidence that they are affected from clinical testing. Given the risk of life threatening arrhythmia as a first presentation of disease expression, enhanced detection of ventricular arrhythmia would help to identify patients with manifest ARVC.

The PREPARE study will test the hypothesis that prolonged monitoring with an implantable loop recorder (ILR) will provide evidence of progressive electrical disease in gene positive ARVC patients with a non-diagnostic phenotype (negative or mild) who do not receive an implantable cardioverter defibrillator (ICD). Detection of non-sustained ventricular tachycardia will have incremental value over routine periodic clinical follow-up and standard short term monitoring (24-48 hour Holter).

Sponsor: Lawson Health Research Institute

Current Primary Outcome: Detection of ≥8 beats of wide QRS complex tachycardia considered ventricular tachycardia (HR>120 bpm*) by the ILR [ Time Frame: 3 year monitoring follow-up ]

* an algorithm to determine the ventricular tachycardia detection rate


Original Primary Outcome: Detection of ≥8 beats of wide QRS complex tachycardia considered ventricular tachycardia (HR>120 bpm*) by the ILR [ Time Frame: 3 year monitoring follow-up ]

Current Secondary Outcome:

  • Comparison of ventricular arrhythmia burden between routine [ Time Frame: 3 year monitoring follow-up ]
    * an algorithm to determine the ventricular tachycardia detection rate
  • Change in 2010 Task Force Criteria Score from enrollment to 3-year follow-up. [ Time Frame: 3 year monitoring follow-up ]
  • Detection of ≥30 seconds of wide QRS complex tachycardia considered ventricular tachycardia (HR>120 bpm*). [ Time Frame: 3 year monitoring follow-up ]
  • Proportion of patients that go on to receive an ICD [ Time Frame: 3 year monitoring follow-up ]
  • Proportion of patients that develop symptomatic sustained ventricular tachycardia [ Time Frame: 3 year monitoring follow-up ]
  • Proportion of patients that develop sustained ventricular tachycardia, cardiac arrest or sudden death [ Time Frame: 3 year monitoring follow-up ]


Original Secondary Outcome:

  • Comparison of ventricular arrhythmia burden between routine surveillance Holter monitoring and the ILR [ Time Frame: 3 year monitoring follow-up ]
  • Change in 2010 Task Force Criteria Score from enrollment to 3-year follow-up. [ Time Frame: 3 year monitoring follow-up ]
  • Detection of ≥30 seconds of wide QRS complex tachycardia considered ventricular tachycardia (HR>120 bpm*). [ Time Frame: 3 year monitoring follow-up ]
  • Proportion of patients that go on to receive an ICD [ Time Frame: 3 year monitoring follow-up ]
  • Proportion of patients that develop symptomatic sustained ventricular tachycardia [ Time Frame: 3 year monitoring follow-up ]
  • Proportion of patients that develop sustained ventricular tachycardia, cardiac arrest or sudden death [ Time Frame: 3 year monitoring follow-up ]


Information By: Lawson Health Research Institute

Dates:
Date Received: January 4, 2011
Date Started: December 2010
Date Completion:
Last Updated: January 2, 2014
Last Verified: January 2014