The Predictive Value of Dobutamine Echo-stress in the Clinical Response to CCM Therapy in Advanced HF

NCT06973902 | Recruiting FDA Device

• 1 other identifier: PREDICT-CCM
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 13

Brief Summary

The goal of this observational cohort study, which is both retrospective and prospective, is to evaluate the long-term clinical and instrumental response to Cardiac Contractility Modulation (CCM) treatment in adult subjects suffering from symptomatic heart failure (HF) due to systolic left ventricular dysfunction, despite adequate medical therapy. Based on the response to stress echocardiography with preimplantation low-dose Dobutamine, the main questions it aims to answer are:

• What is the proportion of subjects who experience a clinical response to CCM therapy at 12 months (NYHA reduction ≥ 1 class)?
• There was a reduction in the number of hospitalizations, visits to the Emergency Department, and access to day hospital facilities for more than 4 hours compared to the year before the study (e.g., by intravenous infusion of cardiac inotropic drugs)?
• What is the estimated change in the quality-of-life score using the "Quality of Life Questionnaire with Heart Failure - Minnesota" (MLHFQ) between baseline and the end of follow-up?
• What is the change in walking distance between baseline and the end of the follow-up in the walk test (6MWT) (optional)?
• What is the difference in NT-proBNP levels between baseline and the end of follow-up? Participants are already receiving CCM support as part of their regular medical care for heart failure.

Conditions

Symptomatic Congestive Heart Failure

Keywords

Heart failure; systolic left ventricular dysfunction; low-dose dobutamine stress echocardiography; Cardiac Contractility Modulation (CCM)

Outcome Measures

Primary Outcomes (1)

• New York Heart Association class variation

  The proportion of subjects with clinical response to CCM therapy at 12 months, defined as a reduction of at least 1 class of the New York Heart Association Classification of the functional status of the heart (minimum value I, better outcome, and maximum value IV, worse outcome)

  From enrollment to the end of follow-up, 12 months

Secondary Outcomes (14)

• Hospitalizations

  From enrollment to the end of follow-up, 12 months

• Minnesota LIVING WITH HEART FAILURE Questionnaire score variation

  From enrollment to the end of follow-up, 12 months

• 6MWT variation

  From enrollment to the end of follow-up, 12 months

• NT-proBNP variation

  From enrollment to the end of follow-up, 12 months

• LVESV change

  From enrollment to the end of follow-up, 12 months

Study Arms (2)

DeltaESV>=15%

Subjects showing a reduction of 15% or more in LVESV through pre-implant low-dose dobutamine echocardiography stress testing

Device: Cardiac Contractility Modulation (CCM) implant

DeltaESV<15%

Subjects showing a reduction of less than 15% in LVESV through pre-implant low-dose dobutamine echocardiography stress testing

Device: Cardiac Contractility Modulation (CCM) implant

Interventions

Cardiac Contractility Modulation (CCM) implant DEVICE

Subjects participating in the study carry or will carry the Cardiac Contractility Modulation (CCM) medical device "OPTIMIZER Smart Mini" by Impulse Dynamics (USA). It is indicated for use in patients over 18 years of age with symptomatic heart failure due to systolic left ventricular dysfunction, despite appropriate medical treatment. The OPTIMIZER Smart Mini Implantable Pulse Generator is a programmable device with an internal battery and telemetry functions. The OPTIMIZER Smart Mini is connected to two or three implantable leads, two of which are implanted in the right ventricle and one, optionally, in the right atrium.

DeltaESV<15%; DeltaESV>=15%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Enrollable subjects who, in the participating Clinical Centers, received a CCM implant from July 1, 2024, to the start of the study will be part of the retrospective cohort, while subsequent subjects of the prospective cohort.

You may qualify if:

• Subject of both sexes with age ≥ 18 years,
• Ability to understand and sign informed consent to participate in the study and consent to process sensitive personal data.
• Carrier of symptomatic heart failure, despite optimal medical therapy (OMT),
• Reduced left ventricular systolic function (E.F. \<50%),
• It was positively evaluated for implanting a system for cardiac contractility modulation (CCM) (according to the European Society of Cardiology 2021 Guidelines on heart failure and the provisions of the C.E. mark approval)13.
• Have presented at least one hospitalization, access to the Emergency Department, or access to day hospital facilities for more than 4 hours (e.g., by intravenous infusion of cardiac inotropic drugs) in the year before implantation

You may not qualify if:

• Life expectancy \< 1 year due to non-cardiac comorbidities that reduce prognosis,
• Presence of contraindications to the CCM implantation procedure (absence of vascular access usable for CCM implantation, active infectious processes, active severe coagulopathies, presence of mechanical tricuspid valve),
• Contraindications to the performance of the echocardiographic test under pharmacological stress (heart failure in progress, myocardial infarction in the acute phase, acute inflammatory processes of the heart muscle and/or pericardium, critical aortic valve stenosis and severe obstructions to left ventricular outflow, dissecting aneurysm of the aorta, severe arrhythmias not controlled by therapy, known hypersensitivity to the drug, intraventricular thrombi).

Sponsors & Collaborators

• Quovadis Associazione: lead
• Impulse Dynamics: collaborator

Study Sites (13)

PO Anastasia Guerriero, Marcianise (CE), UOC Cardiologia

Marcianise, Campania, Italy

RECRUITING

Clinica Montevergine, Mercogliano (AV), Laboratorio di Elettrofisiologia

Mercogliano, Campania, Italy

RECRUITING

UOC Cardiologia, Osp. San Rocco, Sessa Aurunca (CE), ASL Caserta

Sessa Aurunca, Campania, Italy

RECRUITING

Policlinico S.Orsola, UO Cardiologia

Bologna, Emilia-Romagna, Italy

RECRUITING

OSPEDALE CASTELLI, UO Cardiologia

Anzio, Lazio, Italy

RECRUITING

Elettrofisiologia e Aritmologia, ASST FBF Sacco

Milan, Lombardy, Italy

RECRUITING

Fondazione Giglio, Cefalù (PA), UOC Cardiologia

Cefalù, Sicily, Italy

RECRUITING

Osp. Generale Provinciale Mazzoni, UO Cardiologia

Ascoli Piceno, The Marches, Italy

ACTIVE NOT RECRUITING

UOC Cardiologia, Osp. Di Mirano, ULSS 3 Serenissima

Mirano, Veneto, Italy

RECRUITING

UOC Cardiologia, Osp. Di Piove di Sacco (PD), ULSS 6 Euganea

Piove di Sacco, Veneto, Italy

RECRUITING

UOC Cardiologia, Osp. S.Bortolo, Vicenza, ULSS 8 Berica

Vicenza, Veneto, Italy

RECRUITING

UOC Cardiologia con UTIC, Osp. Di Venere

Bari, 70131, Italy

RECRUITING

UO Cardiologia, S. Maria della Misericordia Hospital, ULSS5 Polesana

Rovigo, 45100, Italy

RECRUITING

Related Publications (17)

• Rector, T., S. Kubo, and J. Cohn, Patient's self-assessment of their congestive heart failure. Part 2: content, reliability and validity of a new measure, The Minnesota Living with Heart Failure Questionnaire. Heart Failure. Heart Failure, 1987; 1:198-209

  BACKGROUND

• Nagele H, Behrens S, Eisermann C. Cardiac contractility modulation in non-responders to cardiac resynchronization therapy. Europace. 2008 Dec;10(12):1375-80. doi: 10.1093/europace/eun257. Epub 2008 Sep 5.

  PMID: 18776196 BACKGROUND

• Matsumura Y, Takata J, Kitaoka H, Hamada T, Okawa M, Kubo T, Doi Y. Low-dose dobutamine stress echocardiography predicts the improvement of left ventricular systolic function and long-term prognosis in patients with idiopathic dilated cardiomyopathy. J Med Ultrason (2001). 2006 Mar;33(1):17-22. doi: 10.1007/s10396-005-0061-z.

  PMID: 27277614 BACKGROUND

• Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG; American Society of Echocardiography. American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr. 2007 Sep;20(9):1021-41. doi: 10.1016/j.echo.2007.07.003. No abstract available.

  PMID: 17765820 BACKGROUND

• Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, Voigt JU, Zamorano JL; European Association of Echocardiography. Stress echocardiography expert consensus statement: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J Echocardiogr. 2008 Jul;9(4):415-37. doi: 10.1093/ejechocard/jen175.

  PMID: 18579481 BACKGROUND

• Narducci ML, Nurchis MC, Ballacci F, Giordano F, Calabro GE, Massetti M, Crea F, Aspromonte N, Damiani G. Cost-utility of cardiac contractility modulation in patients with heart failure with reduced ejection fraction in Italy. ESC Heart Fail. 2024 Feb;11(1):229-239. doi: 10.1002/ehf2.14538. Epub 2023 Nov 9.

  PMID: 37943287 BACKGROUND

• Witte K, Hasenfuss G, Kloppe A, Burkhoff D, Green M, Moss J, Peel A, Mealing S, Durand Zaleski I, Cowie MR. Cost-effectiveness of a cardiac contractility modulation device in heart failure with normal QRS duration. ESC Heart Fail. 2019 Dec;6(6):1178-1187. doi: 10.1002/ehf2.12526.

  PMID: 31997539 BACKGROUND

• Mullens W, Dauw J, Gustafsson F, Mebazaa A, Steffel J, Witte KK, Delgado V, Linde C, Vernooy K, Anker SD, Chioncel O, Milicic D, Hasenfuss G, Ponikowski P, von Bardeleben RS, Koehler F, Ruschitzka F, Damman K, Schwammenthal E, Testani JM, Zannad F, Bohm M, Cowie MR, Dickstein K, Jaarsma T, Filippatos G, Volterrani M, Thum T, Adamopoulos S, Cohen-Solal A, Moura B, Rakisheva A, Ristic A, Bayes-Genis A, Van Linthout S, Tocchetti CG, Savarese G, Skouri H, Adamo M, Amir O, Yilmaz MB, Simpson M, Tokmakova M, Gonzalez A, Piepoli M, Seferovic P, Metra M, Coats AJS, Rosano GMC. Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC). Eur J Heart Fail. 2024 Feb;26(2):483-501. doi: 10.1002/ejhf.3150. Epub 2024 Jan 25.

  PMID: 38269474 BACKGROUND

• Authors/Task Force Members:; McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022 Jan;24(1):4-131. doi: 10.1002/ejhf.2333.

  PMID: 35083827 BACKGROUND

• Borggrefe M, Burkhoff D. Clinical effects of cardiac contractility modulation (CCM) as a treatment for chronic heart failure. Eur J Heart Fail. 2012 Jul;14(7):703-12. doi: 10.1093/eurjhf/hfs078. Epub 2012 Jun 12.

  PMID: 22696514 BACKGROUND

• Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, Mann DL, Saville B, Parise H, Chan R, Wiegn P, Hastings JL, Kaplan AJ, Edelmann F, Luthje L, Kahwash R, Tomassoni GF, Gutterman DD, Stagg A, Burkhoff D, Hasenfuss G. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC Heart Fail. 2018 Oct;6(10):874-883. doi: 10.1016/j.jchf.2018.04.010. Epub 2018 May 10.

  PMID: 29754812 BACKGROUND

• Abraham WT, Nademanee K, Volosin K, Krueger S, Neelagaru S, Raval N, Obel O, Weiner S, Wish M, Carson P, Ellenbogen K, Bourge R, Parides M, Chiacchierini RP, Goldsmith R, Goldstein S, Mika Y, Burkhoff D, Kadish A; FIX-HF-5 Investigators and Coordinators. Subgroup analysis of a randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. J Card Fail. 2011 Sep;17(9):710-7. doi: 10.1016/j.cardfail.2011.05.006. Epub 2011 Jun 22.

  PMID: 21872139 BACKGROUND

• Kadish A, Nademanee K, Volosin K, Krueger S, Neelagaru S, Raval N, Obel O, Weiner S, Wish M, Carson P, Ellenbogen K, Bourge R, Parides M, Chiacchierini RP, Goldsmith R, Goldstein S, Mika Y, Burkhoff D, Abraham WT. A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. Am Heart J. 2011 Feb;161(2):329-337.e1-2. doi: 10.1016/j.ahj.2010.10.025.

  PMID: 21315216 BACKGROUND

• Borggrefe MM, Lawo T, Butter C, Schmidinger H, Lunati M, Pieske B, Misier AR, Curnis A, Bocker D, Remppis A, Kautzner J, Stuhlinger M, Leclerq C, Taborsky M, Frigerio M, Parides M, Burkhoff D, Hindricks G. Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure. Eur Heart J. 2008 Apr;29(8):1019-28. doi: 10.1093/eurheartj/ehn020. Epub 2008 Feb 12.

  PMID: 18270213 BACKGROUND

• Campbell CM, Kahwash R, Abraham WT. Optimizer Smart in the treatment of moderate-to-severe chronic heart failure. Future Cardiol. 2020 Jan;16(1):13-25. doi: 10.2217/fca-2019-0044. Epub 2019 Dec 9.

  PMID: 31825245 BACKGROUND

• Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC, Coats AJS. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res. 2023 Jan 18;118(17):3272-3287. doi: 10.1093/cvr/cvac013.

  PMID: 35150240 BACKGROUND

• Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KK, Murabito JM, Vasan RS. Long-term trends in the incidence of and survival with heart failure. N Engl J Med. 2002 Oct 31;347(18):1397-402. doi: 10.1056/NEJMoa020265.

  PMID: 12409541 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Ventricular Dysfunction, Left

Interventions

Mutagenesis, Insertional

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Protein Engineering; Genetic Engineering; Genetic Techniques; Investigative Techniques; Mutation; Genetic Variation; Genetic Phenomena; Mutagenesis

Study Officials

• Francesco Zanon, MD

  UO Cardiologia, S. Maria della Misericordia Hospital, ULSS5 Polesana, Rovigo (I)

  STUDY CHAIR

Central Study Contacts

Franco Noventa, MD

CONTACT

+39 049715373; franco.noventa@quovadis-ass.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 15, 2025
• Study Start: July 10, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (13)