Clinical, Electrocardiographic, and Cardiac Magnetic Resonance Imaging Risk Factors Associated with Ventricular Tachyarrhythmias in Nonischemic Cardiomyopathy (MARVEN Study)

  • STATUS
    Recruiting
Updated on 24 November 2020
heart study

Summary

Implantable cardioverter defibrillator (ICD) for primary prevention of mortality is an approved therapy in ischemic and nonischemic cardiomyopathy patients with left ventricular ejection fraction (EF) ≤35%.

However, data from clinical trials leading to this indication in nonischemic cardiomyopathy (NICM) patients were limited.

  • The DEFINITE [1] trial (458 patients; hazard ratio 0.65; p=0.08) and a subgroup analysis of the SCD-HeFT trial [2] (792 patients; hazard ratio = 0.73; p=0.06) showed a non-significant but clinically meaningful reduction in mortality, and significant reductions in sudden cardiac death [1] or tachyarrhythmic mortality [3].
    • These findings served to form a Class I indication with the level evidence B for ICD implantation in nonischemic cardiomyopathy patients [4].
  • The DANISH ICD trial (published in 2016 [5]) showed that randomized 1,116 patients with NICM and EF ≤35% to ICD or no ICD demonstrated lack of significant mortality reduction in ICD patients when compared to non-ICD patients (hazard ratio=0.87; p=0.28), but significant reduction in the risk of sudden cardiac death (hazard ratio=0.50; p=0.005).
    • The DANISH patients were on optimal pharmacological therapy and 58% had CRT devices.

Consistently, DEFINITE, SCD-HeFT, and DANISH trials showed a significant reduction in sudden cardiac or tachyarrhythmia death with ICD, indicating that ICD is beneficial in groups of patients developing tachyarrhythmias that might lead to sudden cardiac death [1-5].

 

Description

Identification of NICM patients who are likely to develop ventricular tachyarrhythmias is challenging.

 

In the light of MADIT-RIT and ADVANCE III trials, modern programming of ICDs is targeting faster (188-200 bpm) and longer (>30 beats) episodes of ventricular tachyarrhythmias, that might serve as the endpoint related to a reduction in sudden cardiac death with ICDs [6, 7].

Data from the MADIT-CRT trial [8,9] in 416 NICM patients in NYHA class II with QRS ≥130 ms who were randomized to CRT-D and who had a 24-hour Holter ECG recording obtained prior to device implantation has served to develop risk stratification model for this study.

Presence of NSVT on preimplantation Holter (observed in 194 [47%] patients) was associated with hazard ratio of 3.08 (p<0.001) for fast VT≥188 bpm or VF, enlarged LVESVi >86 ml/m2 (observed in 50% of patients) with hazard ratio of 2.81 (p<0.001), and Non-LBBB QRS morphology (observed in 44 (11%) patients) with hazard ratio of 3.33 (p<0.001) in a multivariate model predicting fast VT>188 bpm or VF.

 

This risk prediction model utilizing Holter-detected NSVT, LBBB or Non-LBBB QRS morphology, and left ventricular volume provided effective risk stratification that could guide therapeutic decisions regarding implantation of CRT-D, CRT-P, or ICD devices in NICM heart failure patients with QRS≥120 ms, as per current CRT indications.

The above risk model will be validated in this study in 350 NICM patients with wide QRS≥120ms since data from the MADIT-CRT were acquired a decade ago.

There is an increasing interest in assessment of myocardial damage using late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) and the data are encouraging [10-15], showing about a 3-8 fold increase in the risk of SCD in patients with evident myocardial abnormalities by LGE in comparison to those without LGE.

 

CMR offers insight into the extent of myocardial fibrosis that, if combined with electrical markers could greatly improve identification of patients benefiting from an implantable defibrillator as well as those in whom device placement might be deferred.

 

Details
Condition Pacemaker (ICD)
Clinical Study IdentifierTX217964
Last Modified on24 November 2020

Eligibility

Yes No Not Sure

Inclusion Criteria

Age > 21 years
Optimal pharmacologic therapy as defined by published guidelines from the American Heart Association and the American College of Cardiology for at least 3 calendar months after NICM diagnosis
Nonischemic dilated cardiomyopathy meeting current primary prevention indications for CRT-D
QRS ≥ 120 ms for LBBB patients with NYHA class II, III or IV (ambulatory) OR  QRS ≥ 120 ms for non-LBBB patients with NYHA class III or IV (ambulatory), OR  QRS ≥ 150 ms for non-LBBB patients with NYHA class II As evidenced by ECG qualifying patient for CRT-D implant within 12 calendar months prior to consent
LVEF ≤ 35% within 12 calendar months prior to or on consent date by angiographic, cardiac nuclear test, CMR or echocardiographic methods
Sinus rhythm by most recent ECG qualifying patient for CRT-D implant Willingness to undergo CRT-D implant with remote interrogation enabled within 2 calendar months after consent date
Existing CMR within 6 calendar months prior to or on consent date that is of sufficient quality as determined by CMR core lab  If no CMR within 6 calendar months prior to or on consent date or quality of CMR is not sufficient, willingness to undergo CMR imaging testing prior to CRT-D implantation

Exclusion Criteria

Atrial fibrillation or flutter
Clinical history or imaging indication of nonischemic cardiomyopathy due to other known causes including amyloidosis, sarcoidosis, cardiotoxicity due to chemotherapy, hypertrophic cardiomyopathy, ARVC  History of prior myocardial infarction, percutaneous coronary intervention, and coronary bypass grafting; documented by serum markers or imaging modalities
Angiographic evidence of coronary disease that requires coronary revascularization or likelihood of undergoing a CABG or PCI
Upgrade to CRT from ICD or pacemaker
Secondary prevention indication after documented cardiac arrest
Contraindications to having CMR imaging
Severe claustrophobia
Renal insufficiency (GFR ≤ 30 mL/min/1.73m2 within one calendar month prior to CMR) as calculated in a formula comprising of subject serum creatinine with the subjects age, gender and weight. GFR must be >30 mL/min/1.73m2 to proceed with contrast
Known allergy to gadolinium-based contrast
Any medical condition likely to limit survival to < 1 year
Participation in other clinical trials that will affect the objectives of this study
Inability or unwillingness to provide informed consent
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