CTO-PCI in Heart Failure Patients (CTO-HF)

Percutaneous Coronary Intervention in Patients with Chronic Total Occlusion of Coronary Arteries and Heart Failure.

The study investigates wheather CTO-PCI improves survival and heart failure related rehospitalization compared to optimal medical therapy (OMT). This hypothesis will be investigated within a large-scaled international, representative, prospective, randomized, controlled, open-label, event-driven, multicentre trial (trial acronym: CTO - Heart Failure) recruiting patients with planned CTO-PCI.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Heart Failure; Chronic Total Occlusion
• Intervention / Treatment: Procedure: CTO-PCI

Detailed Description

Coronary artery disease (CAD) is the most common cause of heart failure and death worldwide. Beside non-occlusive coronary arterial stenoses, 25% of CAD patients have a so called chronic total occlusion (CTO) at one out of three main coronary arteries. CTO are often left untreated by physicians over many years due to lack of knowledge of its prognostic relevance and due to be too challenging and risky for the interventional cardiologist, particularly in the presence of severe comorbidities such as heart failure. By development of new interventional devices, techniques and algorithms, CTO can be revascularized in more than 90% with low complication rates. Per se, a patient suffering from comorbid heart failure caused by CAD including a CTO is often regarded as inoperable for heart surgery by coronary artery bypass grafting (CABG). Therefore, the only causal alternative therapy represents the less-invasive interventional revascularization of the CTO by percutaneous coronary intervention (PCI). Until now, the prognostic impact of CTO-PCI has never been proven. Our recent work has outlined the beneficial impact of CTO-PCI to improve both left ventricular cardiac function and cardiopulmonary exercise capacity in patients with heart failure. Our objective is to understand whether CTO-PCI improves survival and heart failure related rehospitalization compared to optimal medical therapy (OMT). This hypothesis will be investigated within a large-scaled representative, prospective, randomized, controlled, open-label, event-driven, multicentre trial (trial acronym: CTO - Heart Failure) recruiting patients with planned CTO-PCI. The CTO Heart Failure aims to deliver evidence whether CTO-PCI might become a prognostically relevant established therapeutic option for patients with systolic heart failure.

• Study Type: Interventional
• Enrollment (Estimated): 783
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Behnes, Prof. Dr.; Phone Number: +49 621 383 6239; Email: michael.behnes@umm.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent.
• Presence of at least one CTO located at the proximal to midpart of left artery descending (LAD), or at proximal left circumflex (LCX), or at proximal to midpart LCX in left dominant system, or at proximal to distal right coronary artery (RCA).
• LVEF <50% (assessed within 6 weeks prior to enrolment by transthoracic echocardiography (TTE) (Simpson biplane method) or cardiac magnetic resonance imaging (cMRI).
• In patients with multivessel disease (MVD) and Syntax I score ≥ 22, and all patients with type 2 diabetes and coronary 3 vessel disease, a heart team decision favouring CTO-PCI is needed.
• Mandatory baseline imaging assessment (assessed within 6 weeks prior to enrolment):
• TTE: Normal wall motion or hypokinesia in the CTO-territory.
• In case of severe hypokinesia, akinesia or dyskinesia a viability testing with cMRI or myocardial scintigraphy (MS) indicating at least 50% of viability in the CTO territory (mandatory only in the presence of akinesia in the CTO-territory assessed by prior TTE) prior to PCI is mandatory.
• Symptoms including dyspnea (according to the New York Heart Association (NYHA), classes II-III) or angina pectoris (according to Canadian Cardiovascular Society (CCS), classes II-IV).
• In the absence of symptoms evidence of myocardial ischemia of at least 10% is needed being assessed by invasive or non-invasive imaging, such as stress-MRI, PET-CT-scan, myocardial scintigraphy, stress-echocardiography

Exclusion Criteria:

• Age <18 and >90 years.
• Akinesia or dyskinesia assessed by TTE plus subendocardial late gadolinium enhancement of >50% assessed by cMRI or MS in the CTO-territory or any evidence of transmural scarring of the CTO-territory (i.e. 100%).
• Presence of terminal kidney disease with need for renal replacement therapy.
• Severe chronic kidney disease (defined as GFR < 25 ml/min).
• Type I myocardial infarction (ST segment elevation or non-ST segment elevation myocardial infarction (STEMI or NSTEMI)) related to critical arteriosclerosis < 30 days.
• End-stage heart failure (defined by constant administration of intravenous inotropes, use of prolonged assist devices (more than 5 days), listing for high urgent cardiac transplantation).
• Cardiogenic shock (< 30 days).
• Heart team decision favoring CABG surgery (in the presence of coronary multivessel disease with intermediate to high SYNTAX I score).
• Grade II-III heart valve disorders requiring interventional or surgical treatment within 3 months.
• Right-sided heart failure with echocardiographic evidence of severe right ventricular dysfunction.
• COPD requiring long-term oxygen therapy.
• Non-cardiac comorbidity with life expectancy < 12 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTO-PCI	Procedure: CTO-PCI; Percutaneous coronary intervention (PCI) of a coronary chronic total occlusion (CTO) (CTO-PCI) in patients with systolic heart failure (LVEF <50%).
No Intervention: non-CTO-PCI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of all-cause mortality or heart failure related rehospitalization.	Heart failure related rehospitalization is defined as a rehospitalization due to worsening heart failure requiring intravenous therapy as the primary cause, or as a result of another cause but associated with worsening heart failure at the time of admission, or as a result of another cause but complicated by worsening heart failure during its course	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Canadian cardiovascular society (CCS) class	angina pectoris	up to 3 years
All-cause mortality.		up to 3 years
Heart failure related rehospitalization.		up to 3 years
MACCE	MACCE are defined as the composite of all-cause death, myocardial infarction (type I and II), any further type of coronary revascularization (i.e. PCI or CABG) based on functional invasive assessment by fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), and stroke.	up to 3 years
Number of participanty with rehospitalization due to cardiac diseases beyond heart failure.		up to 3 years
assessment of quality of life	Seattle angina questionnaire (SAQ) (0-100; 75-100 normal).	up to 3 years
cost effectivenes	direct and indirect health care related costs	up to 3 years
Re-assessment of LVEF		up to 3 years
New York Heart association (NYHA) class	dyspnea	up to 36 months

Collaborators and Investigators

• Sponsor: Universitätsmedizin Mannheim
• Collaborators: IHF GmbH - Institut für Herzinfarktforschung; Herzzentrum Lahr
• Investigators: Principal Investigator: Michael Behnes, Prof. Dr., Universitätsmedizin Mannheim; Study Director: Kambis Mashayekhi, PD Dr., MediClin Herzzentrum Lahr

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 15, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Failure; Coronary Artery Disease
• Other Study ID Numbers: 01012022-MA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No