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Dilated CardiomyopathyIMPROVE-NICMNCT06730464

Image-Based Prediction of Ventricular Tachycardia Events in Non-ischemic Cardiomyopathy

An observational study of Dilated Cardiomyopathy and Arrhythmogenic Cardiomyopathy, run by Centro Medico Teknon at 4 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Risk stratification for sudden cardiac death (SCD) in patients with non-ischemic cardiomyopathy (NICM) remains suboptimal. Although current guidelines rely on severe left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) < 35%) as key predictor of arrhythmic risk and clinical indication of… Read more about this study

Who is it for?
Ages 18 years and older
How many people
500 participants
Where
4 sitesin 3 countries
Study dates
7 Oct 2024to 23 Feb 2027
How long will I take part?
2 Years
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients with dilated cardiomyopathy (DCM) or Non-dilated left ventricular cardiomyopathy (NDLVC) or Post-myocarditis cardiomyopathy

Who may be able to join

  • Diagnosis of non-ischemic heart disease involving the left ventricle, irrespectively of LVEF. This diagnosis includes:
  • Dilated cardiomyopathy (DCM)
  • Non-dilated left ventricular cardiomyopathy (NDLVC)
  • Post-myocarditis cardiomyopathy
  • Life expectancy of > 1 year with a good functional status.
  • Signed informed consent.
  • At least one late gadolinium enhancement-cardiac magnetic resonance (LGE-CMR) already performed.
  • No VA events at the time of the 1st LGE-CMR study.

Who cannot join

  • Pregnancy.
  • Life expectancy of < 1 year, or bad functional status (NYHA IV functional class).
  • Other concomitant structural heart diseases (e.g. ischemic, congenital, arrhythmogenic right ventricular cardiomyopathy etc.)
  • No LGE-CMR at time of enrollment or LGE-CMR data not available.
  • Previously documented sustained ventricular arrhythmias at the time of 1st LGE-CMR.
  • Concomitant investigation treatments.
  • Medical, geographical and social factors that make study participation impractical, and inability to give written informed consent. Patient's refusal to participate in the study.

Trial locations and contacts

4 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

4 sites in 3 countries

Spain2 sites, 2 recruiting

  • Teknon Medical Center

    Barcelona, Barcelona, 08022

    Antonio Berruezo, MD, PhD, 669761263, antonio.berruezo@quironsalud.es

    Recruiting

  • Virgen del Rocio University Hospital

    Seville, Sevilla, 41013

    Juan Acosta, MD, PhD, 677851132, juan.acostamartinez@gmail.com

    Recruiting

Other trials in Spain

Italy1 site, 1 recruiting

  • Humanitas Research Hospital (Rozzano - Milan, Italy)

    Milan, Italy, 20089

    Diego Penela, MD, PhD, 34647628720, penela.maceda@gmail.com

    Recruiting

Other trials in Italy

Portugal1 site, 1 recruiting

  • Hospital de la Luz

    Lispon, Portugal, 1500-650

    Antonio Miguel Ferreira, MD, PhD, 351 21 710 4400, miguelferreira.md@sapo.pt

    Recruiting

Other trials in Portugal

About this study

Official title: Image-Based Prediction of Ventricular Tachycardia Events in Non-ischemic Cardiomyopathy, an International Multicenter Study - [The IMPROVE-NICM Study]

Risk stratification for sudden cardiac death (SCD) in patients with non-ischemic cardiomyopathy (NICM) remains suboptimal. Although current guidelines rely on severe left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) < 35%) as key predictor of arrhythmic risk and clinical indication of prophylactic implantable cardioverter defibrillator (ICD), this approach seems inadequate, since registries report that only a minority of NICM ICD carriers experience an appropriate ICD shock during follow-up, whereas out-of-hospital cardiac arrests (OHCA) occur in patients with LVEF>35% in up to 80% of cases. Moreover, pivotal primary prevention trials (DANISH trial, long-term outcome of the SCD-HeFT trial) failed to demonstrate a net mortality benefit of ICD in patients with NICM.

As for most structural heart diseases (SHD), scar-related reentry has been addressed as the pathophysiological mechanism of ventricular arrhythmias (VAs) in patients with NICM, with fibrotic tissue being the substrate of this reentry. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is the gold standard for the non-invasive visualization and characterization of the myocardial fibrosis and according to retrospective studies is detected in nearly 30% of patients with NICM.

Read more

In latest years, several studies and subsequent metanalyses have explored the correlation between CMR-detected LGE and occurrence of VAs, showing that presence, extent, location (septal vs lateral) and patten (focal vs multifocal vs ring-like) of non-ischemic fibrosis help in stratifying arrhythmic risk.

Nonetheless, scar heterogeneity (that is, inherent composition of dense scars vs border zone (BZ), presence of strands of viable myocardium within the scar) has been indicated as a potential novel predictor of VAs. In a recent prospective multicenter registry on patients with class I indication for cardiac resynchronization therapy (CRT) (>60% with NICM), not only scar mass, but even border zone (BZ) mass and presence of BZ channels were identified as independent predictors for VT occurrence in NICM patients.

This BZ mass and BZ channels can be automatically identified using a commercially available, post-processing imaging platform named ADAS 3D LV (ADAS3D Medical SL, Barcelona, Spain), with FDA 510(k) Clearance and CE Mark approval. Thus, CMR-derived BZ mass might be used as an automatically reproducible criterium to reclassify those patients with NICM at highest risk for developing VAs/SCD in a relatively short period of at least 2 years.

In the present cohort study, the investigators sought to: i) evaluate the usefulness of CMR-derived BZ mass measurement and identification of heterogeneous tissue channels (HTC) (among other scar characteristics derived from image post-processing) to predict the occurrence of VT events in an international, retrospective, multicenter, unselected series of patients with NICM without previous arrhythmia evidence (main study); ii) subsequently validate these predictors of VT occurrence in a prospectively-collected multicenter cohort study (substudy 1); iii) retrospectively evaluate in the subset of patients with > 1 LGE-CMR performed as part of standard clinical practice if any change in BZ mass and HTC presence occurs over time and if this correlates with occurrence of VAs (substudy 2).

Read the detailed description

Primary objective To analyze the composite outcome of SCD or sustained VT (either treated by an ICD or documented by any diagnostic method) in patients with NICM and no previous arrhythmia evidence, according to their risk classification by means of number of HCT and BZ mass.

Secondary objectives Substudy 1

To validate the variables retrospectively identified to be predictors of SCD or sustained VT in a prospective cohort of consecutively enrolled patients with NICM and no previous arrhythmia evidence.

Substudy 2 To retrospectively evaluate the evolution of scar characteristics over time and their prognostic implication in the subset of patients fulfilling eligibility criteria of the main project with at least 2 LGE-CMRs available as part of their clinical follow-up.

Main study, substudy 1 and 2

To analyze the relationship between the primary outcome and other variables:

  • LVEF
  • Scar mass
  • BZC mass
  • Core mass
  • Scar location
  • Scar pattern
  • Age
  • Genotype (when this data is available)
Keywords
Dilated cardiomyopathy, Non-dilated left ventricular cardiomyopathy (NDLVC), border zone channels, ventricular arrhythmias
Medical subject headings
Cardiomyopathy, Dilated, Cardiomyopathy, Hypertrophic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT06730464
Study groupRoleWhat they receive
Patients with non ischemic cardiomyopathiesPatients will only be recruited if they fulfill ALL the inclusion criteria: 1. Age > 18 years. 2. Diagnosis of non-ischemic heart disease involving the left ventricle, irrespectively of LVEF. This diagnosis includes: 1. Dilated cardiomyopathy (DCM) 2. Non-dilated left ventricular cardiomyopathy (NDLVC) 3. Post-myocarditis cardiomyopathy 3. Life expectancy of > 1 year with a good functional status. 4. Signed informed consent. 5. CMR already performed or scheduled for clinical purpose (standard clinical practice). 6. No VA events at the time of the 1st LGE-CMR study.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of patients presenting one of sudden cardiac death, sustained ventricular arrhythmia, or defibrillator therapy.

    The primary endpoint will be the clinical composite of sudden cardiac death, or any sustained ventricular arrhythmia, or defibrillator therapy

    Measured: From the inclusion date (first CMR date) up to 100 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2024
  2. Study start7 Oct 2024
  3. Primary completion30 Oct 2026 (estimated)
  4. Study completion23 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Other
Enrolment
500 participants (estimated)
Target duration
2 Years
IDs, dates and publications
ClinicalTrials.gov ID
NCT06730464
Sponsor's protocol ID
IMPROVE-NICM
Acronym
IMPROVE-NICM
Status last verified
Dec 2024
First submitted
2 Dec 2024
Last updated
12 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Leyva F, Taylor RJ, Foley PW, Umar F, Mulligan LJ, Patel K, Stegemann B, Haddad T, Smith RE, Prasad SK. Left ventricular midwall fibrosis as a predictor of mortality and morbidity after cardiac resynchronization therapy in patients with nonischemic cardiomyopathy. J Am Coll Cardiol. 2012 Oct 23;60(17):1659-67. doi: 10.1016/j.jacc.2012.05.054. Epub 2012 Sep 26.

    PubMed 23021326

  • Gulati A, Jabbour A, Ismail TF, Guha K, Khwaja J, Raza S, Morarji K, Brown TD, Ismail NA, Dweck MR, Di Pietro E, Roughton M, Wage R, Daryani Y, O'Hanlon R, Sheppard MN, Alpendurada F, Lyon AR, Cook SA, Cowie MR, Assomull RG, Pennell DJ, Prasad SK. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA. 2013 Mar 6;309(9):896-908. doi: 10.1001/jama.2013.1363.

    PubMed 23462786

  • Di Marco A, Brown PF, Bradley J, Nucifora G, Claver E, de Frutos F, Dallaglio PD, Comin-Colet J, Anguera I, Miller CA, Schmitt M. Improved Risk Stratification for Ventricular Arrhythmias and Sudden Death in Patients With Nonischemic Dilated Cardiomyopathy. J Am Coll Cardiol. 2021 Jun 15;77(23):2890-2905. doi: 10.1016/j.jacc.2021.04.030.

    PubMed 34112317

  • Eichhorn C, Koeckerling D, Reddy RK, Ardissino M, Rogowski M, Coles B, Hunziker L, Greulich S, Shiri I, Frey N, Eckstein J, Windecker S, Kwong RY, Siontis GCM, Grani C. Risk Stratification in Nonischemic Dilated Cardiomyopathy Using CMR Imaging: A Systematic Review and Meta-Analysis. JAMA. 2024 Sep 19;332(18):1535-50. doi: 10.1001/jama.2024.13946. Online ahead of print.

    PubMed 39298146

  • Di Marco A, Anguera I, Schmitt M, Klem I, Neilan TG, White JA, Sramko M, Masci PG, Barison A, Mckenna P, Mordi I, Haugaa KH, Leyva F, Rodriguez Capitan J, Satoh H, Nabeta T, Dallaglio PD, Campbell NG, Sabate X, Cequier A. Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy: Systematic Review and Meta-Analysis. JACC Heart Fail. 2017 Jan;5(1):28-38. doi: 10.1016/j.jchf.2016.09.017. Epub 2016 Dec 21.

    PubMed 28017348

  • Halliday BP, Baksi AJ, Gulati A, Ali A, Newsome S, Izgi C, Arzanauskaite M, Lota A, Tayal U, Vassiliou VS, Gregson J, Alpendurada F, Frenneaux MP, Cook SA, Cleland JGF, Pennell DJ, Prasad SK. Outcome in Dilated Cardiomyopathy Related to the Extent, Location, and Pattern of Late Gadolinium Enhancement. JACC Cardiovasc Imaging. 2019 Aug;12(8 Pt 2):1645-1655. doi: 10.1016/j.jcmg.2018.07.015. Epub 2018 Sep 12.

    PubMed 30219397

  • Acosta J, Fernandez-Armenta J, Borras R, Anguera I, Bisbal F, Marti-Almor J, Tolosana JM, Penela D, Andreu D, Soto-Iglesias D, Evertz R, Matiello M, Alonso C, Villuendas R, de Caralt TM, Perea RJ, Ortiz JT, Bosch X, Serra L, Planes X, Greiser A, Ekinci O, Lasalvia L, Mont L, Berruezo A. Scar Characterization to Predict Life-Threatening Arrhythmic Events and Sudden Cardiac Death in Patients With Cardiac Resynchronization Therapy: The GAUDI-CRT Study. JACC Cardiovasc Imaging. 2018 Apr;11(4):561-572. doi: 10.1016/j.jcmg.2017.04.021. Epub 2017 Aug 2.

    PubMed 28780194

  • Lehrke S, Lossnitzer D, Schob M, Steen H, Merten C, Kemmling H, Pribe R, Ehlermann P, Zugck C, Korosoglou G, Giannitsis E, Katus HA. Use of cardiovascular magnetic resonance for risk stratification in chronic heart failure: prognostic value of late gadolinium enhancement in patients with non-ischaemic dilated cardiomyopathy. Heart. 2011 May;97(9):727-32. doi: 10.1136/hrt.2010.205542. Epub 2010 Nov 20.

    PubMed 21097819

  • Halliday BP, Cleland JGF, Goldberger JJ, Prasad SK. Personalizing Risk Stratification for Sudden Death in Dilated Cardiomyopathy: The Past, Present, and Future. Circulation. 2017 Jul 11;136(2):215-231. doi: 10.1161/CIRCULATIONAHA.116.027134.

    PubMed 28696268

  • Dukkipati SR, Koruth JS, Choudry S, Miller MA, Whang W, Reddy VY. Catheter Ablation of Ventricular Tachycardia in Structural Heart Disease: Indications, Strategies, and Outcomes-Part II. J Am Coll Cardiol. 2017 Dec 12;70(23):2924-2941. doi: 10.1016/j.jacc.2017.10.030.

    PubMed 29216988

  • Poole JE, Olshansky B, Mark DB, Anderson J, Johnson G, Hellkamp AS, Davidson-Ray L, Fishbein DP, Boineau RE, Anstrom KJ, Reinhall PG, Packer DL, Lee KL, Bardy GH; SCD-HeFT Investigators. Long-Term Outcomes of Implantable Cardioverter-Defibrillator Therapy in the SCD-HeFT. J Am Coll Cardiol. 2020 Jul 28;76(4):405-415. doi: 10.1016/j.jacc.2020.05.061.

    PubMed 32703511

  • Kober L, Thune JJ, Nielsen JC, Haarbo J, Videbaek L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjaer H, Brandes A, Thogersen AM, Gustafsson F, Egstrup K, Videbaek R, Hassager C, Svendsen JH, Hofsten DE, Torp-Pedersen C, Pehrson S; DANISH Investigators. Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. N Engl J Med. 2016 Sep 29;375(13):1221-30. doi: 10.1056/NEJMoa1608029. Epub 2016 Aug 27.

    PubMed 27571011

  • Gorgels AP, Gijsbers C, de Vreede-Swagemakers J, Lousberg A, Wellens HJ. Out-of-hospital cardiac arrest--the relevance of heart failure. The Maastricht Circulatory Arrest Registry. Eur Heart J. 2003 Jul;24(13):1204-9. doi: 10.1016/s0195-668x(03)00191-x.

    PubMed 12831814

  • Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, Calkins H, Hoch D, Goldberger J, Shalaby A, Sanders WE, Schaechter A, Levine JH; Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004 May 20;350(21):2151-8. doi: 10.1056/NEJMoa033088.

    PubMed 15152060

  • Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA, Charron P, Corrado D, Dagres N, de Chillou C, Eckardt L, Friede T, Haugaa KH, Hocini M, Lambiase PD, Marijon E, Merino JL, Peichl P, Priori SG, Reichlin T, Schulz-Menger J, Sticherling C, Tzeis S, Verstrael A, Volterrani M; ESC Scientific Document Group. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 Oct 21;43(40):3997-4126. doi: 10.1093/eurheartj/ehac262. No abstract available.

    PubMed 36017572

Questions about this trial

What is this clinical trial studying?

An observational study of Dilated Cardiomyopathy and Arrhythmogenic Cardiomyopathy, run by Centro Medico Teknon at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Spain, Italy, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients presenting one of sudden cardiac death, sustained ventricular arrhythmia, or defibrillator therapy. (time frame: From the inclusion date (first CMR date) up to 100 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06730464, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2024.

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