Reversal of Cardiomyopathy by Suppression of Frequent Premature Ventricular Complexes

NCT ID: NCT01566344

Last Updated: 2015-04-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2016-12-31

Brief Summary

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Frequent monomorphic premature ventricular complexes (PVCs) may cause a cardiomyopathy (CMP) that is reversible by suppression of the ectopic focus. This study investigates whether PVC suppression therapy can improve cardiac function and clinical condition of patients with idiopathic or ischemic CMP and frequent monomorphic PVCs. For this purpose, patients will be randomized to either one of two treatment strategies: 1) conventional heart failure therapy plus PVC suppression therapy, consisting of RFCA as primary treatment and Amiodarone as secondary treatment in case of unsuccessful RFCA, or 2) conventional heart failure therapy without PVC suppression therapy.

Detailed Description

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Heart failure accounts for substantial morbidity and mortality in the western world. In addition, the financial burden associated with the disease is considerable. Prognosis is generally poor and quality of life is significantly reduced. The causes of heart failure are diverse. Identification of the underlying pathophysiological mechanism is essential, because a specific patient tailored therapy may help to improve the clinical status of the individual patient. In addition, some patients may have a potentially reversible cardiomyopathy (CMP). The present study will focus on the role of frequent premature ventricular contractions (PVCs) as a cause of left ventricular (LV) dysfunction. This is a potential reversible CMP generally unknown to the cardiological society.

Frequent ventricular ectopy in patients without structural heart disease is generally thought to be a benign finding with no prognostic significance. Suppression of PVCs with anti-arrhythmic drugs or catheter ablation is therefore usually only considered when PVCs are accompanied by disabling symptoms. However, recent data suggest that frequent monomorphic PVCs (symptomatic or asymptomatic) can cause a form of CMP that may be reversible by suppression of the ectopic focus. Furthermore, the high prevalence of frequent PVCs in patients with heart disease suggests that PVC-induced CMP may be a common phenomenon. Suppression of frequent monomorphic PVCs to improve LV systolic function may therefore emerge as a new and effective treatment strategy for patients with heart failure.

Beta-blockers are safe and effective anti-arrhythmic agents and are considered the first line therapy for suppression of PVCs. Most patients with HF are already taking a beta-blocker as part of standard therapy for their underlying disease. According to international guidelines, other AADs can be used if beta-blockers are ineffective, but they have potential adverse (arrhythmic) side-effects, especially in patients with diminished LV function, and may even be contra-indicated in this patient group. In patients with LV dysfunction and frequent monomorphic PVCs that are refractory to beta-blockers, long-term drug therapy and the potential adverse (arrhythmic) side-effects of AADs can be avoided by using catheter ablation as a first alternative treatment. RFCA is already a frequently applied, widely accepted, safe, effective and potentially curative treatment for symptomatic drug refractory PVCs. It has also been safely and effectively employed in patients with tachycardia-induced CMP and patients with PVC-induced CMP. A high acute success rate of 93% and a very low PVC recurrence rate of 3% have been reported. Although recent available data suggest that elimination of the PVC source by RFCA improves LV systolic function in HF patients, it is still applied in a limited fashion for this indication because the evidence supporting this is weak. The patient series published so far were not controlled and retrospective in nature. We intend to conduct a controlled, randomized, prospective study with careful documentation and long-term follow-up to evaluate the effect of PVC suppression therapy (with RFCA as primary treatment) on cardiac systolic function in patients with CMP and beta-blocker refractory frequent monomorphic PVCs. This could establish suppression of frequent monomorphic PVCs as a potential curative treatment strategy for patients with HF.

Conditions

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Heart Diseases Cardiac Arrhythmias Ventricular Premature Complexes Systolic Heart Failure Cardiomyopathies

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Routine heart failure therapy plus PVC suppression therapy

Group Type EXPERIMENTAL

PVC suppression therapy

Intervention Type OTHER

Conventional heart failure therapy plus radiofrequency catheter ablation of PVCs as primary treatment and Amiodarone (tablets, loading dose of 600 mg per day for 4 weeks and 200 mg per day afterwards for at least 12 months) as secondary treatment in case of unsuccessful catheter ablation.

Routine heart failure therapy

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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PVC suppression therapy

Conventional heart failure therapy plus radiofrequency catheter ablation of PVCs as primary treatment and Amiodarone (tablets, loading dose of 600 mg per day for 4 weeks and 200 mg per day afterwards for at least 12 months) as secondary treatment in case of unsuccessful catheter ablation.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. LVEF \< 50% without identifiable cause (idiopathic) or post-infarction, \> 6 months.
2. Optimal conventional heart failure therapy \> 3 months.
3. Frequent monomorphic PVCs on Holter monitoring.

* Frequent = more than 15% of all QRS complexes are PVCs.
* Monomorphic = more than 75% of PVCs have the same morphology.
4. Greater than 18 years of age.
5. Willing and capable of giving informed consent.

Exclusion Criteria

1. Other causes of LV systolic dysfunction:

* Significant valvular disease.
* Untreated hypertension (blood pressure \> 140 mmHg).
* Primary CMP (HCM, ARVC, LVNC, myocarditis, stress, peripartum).
* Secondary CMP (infiltrative, storage, toxic, neuromuscular/neurological, autoimmune).
2. Electrocardiographic PVC characteristics suggestive of a focal origin not accessible by percutaneous approach.
3. Sustained supra-ventricular arrhythmia.
4. Evidence of significant CAD (\>70% stenosis of a coronary artery) on coronary angiogram (CAG) or coronary CT necessitating revascularization (PCI / CABG) in the foreseeable future.
5. Signs of current myocardial ischemia on ECG (dynamic STT segments) or during exercise testing (significant ST segment depression/elevation).
6. Myocardial infarction within the last 6 calender months prior to enrollment.
7. PCI / CABG within the last 6 calender months prior to enrollment.
8. Physical status not allowing electrophysiological study (e.g. pregnancy or severe peripheral artery disease)
9. Presence of any disease, other than the patient's cardiac disease, associated with a reduced likelihood of survival for the duration of the trial.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Maastricht University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yuri Blaauw, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Centre

Harry JGM Crijns, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Centre

Locations

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Maastricht University Medical Centre

Maastricht, Limburg, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Masih Mafi Rad, MD

Role: CONTACT

+31-43-3871613

Yuri Blaauw, MD, PhD

Role: CONTACT

+31-43-3877095

Facility Contacts

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Masih Mafi Rad, MD

Role: primary

+31-43-3871613

Yuri Blaauw, MD, PhD

Role: backup

+31-43-3877095

References

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Bogun F, Crawford T, Reich S, Koelling TM, Armstrong W, Good E, Jongnarangsin K, Marine JE, Chugh A, Pelosi F, Oral H, Morady F. Radiofrequency ablation of frequent, idiopathic premature ventricular complexes: comparison with a control group without intervention. Heart Rhythm. 2007 Jul;4(7):863-7. doi: 10.1016/j.hrthm.2007.03.003. Epub 2007 Mar 12.

Reference Type BACKGROUND
PMID: 17599667 (View on PubMed)

Takemoto M, Yoshimura H, Ohba Y, Matsumoto Y, Yamamoto U, Mohri M, Yamamoto H, Origuchi H. Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilation and clinical status in patients without structural heart disease. J Am Coll Cardiol. 2005 Apr 19;45(8):1259-65. doi: 10.1016/j.jacc.2004.12.073.

Reference Type BACKGROUND
PMID: 15837259 (View on PubMed)

Baman TS, Lange DC, Ilg KJ, Gupta SK, Liu TY, Alguire C, Armstrong W, Good E, Chugh A, Jongnarangsin K, Pelosi F Jr, Crawford T, Ebinger M, Oral H, Morady F, Bogun F. Relationship between burden of premature ventricular complexes and left ventricular function. Heart Rhythm. 2010 Jul;7(7):865-9. doi: 10.1016/j.hrthm.2010.03.036. Epub 2010 Mar 27.

Reference Type BACKGROUND
PMID: 20348027 (View on PubMed)

Yokokawa M, Kim HM, Good E, Chugh A, Pelosi F Jr, Alguire C, Armstrong W, Crawford T, Jongnarangsin K, Oral H, Morady F, Bogun F. Relation of symptoms and symptom duration to premature ventricular complex-induced cardiomyopathy. Heart Rhythm. 2012 Jan;9(1):92-5. doi: 10.1016/j.hrthm.2011.08.015. Epub 2011 Aug 17.

Reference Type BACKGROUND
PMID: 21855522 (View on PubMed)

Sarrazin JF, Labounty T, Kuhne M, Crawford T, Armstrong WF, Desjardins B, Good E, Jongnarangsin K, Chugh A, Oral H, Pelosi F, Morady F, Bogun F. Impact of radiofrequency ablation of frequent post-infarction premature ventricular complexes on left ventricular ejection fraction. Heart Rhythm. 2009 Nov;6(11):1543-9. doi: 10.1016/j.hrthm.2009.08.004. Epub 2009 Aug 5.

Reference Type BACKGROUND
PMID: 19879531 (View on PubMed)

Blaauw Y, Pison L, van Opstal JM, Dennert RM, Heesen WF, Crijns HJ. Reversal of ventricular premature beat induced cardiomyopathy by radiofrequency catheter ablation. Neth Heart J. 2010 Oct;18(10):493-8. doi: 10.1007/BF03091821.

Reference Type BACKGROUND
PMID: 20978594 (View on PubMed)

Niwano S, Wakisaka Y, Niwano H, Fukaya H, Kurokawa S, Kiryu M, Hatakeyama Y, Izumi T. Prognostic significance of frequent premature ventricular contractions originating from the ventricular outflow tract in patients with normal left ventricular function. Heart. 2009 Aug;95(15):1230-7. doi: 10.1136/hrt.2008.159558. Epub 2009 May 7.

Reference Type BACKGROUND
PMID: 19429571 (View on PubMed)

Kanei Y, Friedman M, Ogawa N, Hanon S, Lam P, Schweitzer P. Frequent premature ventricular complexes originating from the right ventricular outflow tract are associated with left ventricular dysfunction. Ann Noninvasive Electrocardiol. 2008 Jan;13(1):81-5. doi: 10.1111/j.1542-474X.2007.00204.x.

Reference Type BACKGROUND
PMID: 18234010 (View on PubMed)

Duffee DF, Shen WK, Smith HC. Suppression of frequent premature ventricular contractions and improvement of left ventricular function in patients with presumed idiopathic dilated cardiomyopathy. Mayo Clin Proc. 1998 May;73(5):430-3. doi: 10.1016/S0025-6196(11)63724-5.

Reference Type BACKGROUND
PMID: 9581582 (View on PubMed)

Yarlagadda RK, Iwai S, Stein KM, Markowitz SM, Shah BK, Cheung JW, Tan V, Lerman BB, Mittal S. Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract. Circulation. 2005 Aug 23;112(8):1092-7. doi: 10.1161/CIRCULATIONAHA.105.546432. Epub 2005 Aug 15.

Reference Type BACKGROUND
PMID: 16103234 (View on PubMed)

Taieb JM, Maury P, Shah D, Duparc A, Galinier M, Delay M, Morice R, Alfares A, Barnay C. Reversal of dilated cardiomyopathy by the elimination of frequent left or right premature ventricular contractions. J Interv Card Electrophysiol. 2007 Nov;20(1-2):9-13. doi: 10.1007/s10840-007-9157-2. Epub 2007 Oct 17.

Reference Type BACKGROUND
PMID: 17940858 (View on PubMed)

Kennedy HL, Whitlock JA, Sprague MK, Kennedy LJ, Buckingham TA, Goldberg RJ. Long-term follow-up of asymptomatic healthy subjects with frequent and complex ventricular ectopy. N Engl J Med. 1985 Jan 24;312(4):193-7. doi: 10.1056/NEJM198501243120401.

Reference Type BACKGROUND
PMID: 2578212 (View on PubMed)

Other Identifiers

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METC 11-2-076

Identifier Type: OTHER

Identifier Source: secondary_id

NL37355.068.11

Identifier Type: -

Identifier Source: org_study_id

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