Predicting Functional Recovery After Coronary Chronic Total Occlusion Revascularization (StressECHOCTO)

Assiut University

Status: Enrolling

Conditions: Inflammation Biomarkers; Chronic Total Occlusions of Coronary Arteries; Stress Echocardiography (SE)

Study type: Observational

Funder types: Other

Identifiers

NCT07879573

StressECHOCTO

Details and patient eligibility

About

Chronic total occlusion (CTO) is defined as complete coronary occlusion with TIMI flow grade 0 persisting for more than three months, identified in 15-25% of patients undergoing coronary angiography.¹,² CTO is associated with refractory angina, left ventricular dysfunction, and increased long-term mortality.³ Revascularization aims to restore anterograde flow and improve myocardial perfusion; however, functional recovery-a patient-centered endpoint-remains variable and poorly predicted.⁴ ,⁵ Available data demonstrate that left ventricular ejection fraction (LVEF) alone is insufficient.⁵ ,⁶ Cardiac magnetic resonance (CMR)-derived extracellular volume predicts recovery (OR 0.38; p=0.019), but CMR is not universally accessible.⁷ Stress echocardiography-derived myocardial work indices (GWI, GCW, GWE, GWW) have been validated in non-CTO populations, detecting dysfunction independent of LVEF and GLS, yet remain unstudied in CTO.⁸ ,⁹ Inflammatory biomarkers-monocyte-to-HDL ratio (MHR), soluble ST2 (sST2), and PIIINP-have shown prognostic value individually, but have not been integrated with myocardial work or procedural data.¹⁰ ,¹¹,¹² Procedural technique (antegrade vs. retrograde) affects procedural success but has not been evaluated as an independent predictor of functional recovery.¹³,¹⁴ The current strategy relies on fragmented, single-domain predictors, with no integrated pre-procedural model.

This research addresses that gap by combining mechanical (myocardial work), biological (MHR, sST2, PIIINP), and technical (procedural technique) domains into a unified predictive model. The rationale is that functional recovery is multifactorial, and an integrated model will outperform single-domain approaches, enabling better patient selection, procedural planning, and expectation setting.

Full description

Chronic total occlusion (CTO) is defined as a complete coronary artery occlusion with TIMI flow grade 0, known or suspected to have lasted for more than 3 months.¹ CTOs are identified in 15-25% of patients undergoing coronary angiography, representing a substantial and growing patient population.²,³ Clinical Consequences of CTOs

Clinical Consequences of CTOs:

Consequence Impact Angina Refractory to medical therapy in up to 40% of patients Left Ventricular Dysfunction Resulting from hibernation, stunning, and irreversible scar burden Mortality Independent predictor of long-term mortality 4 .

Quality of Life Impaired physical capacity and overall well-being

1.2 The Promise and Uncertainty of Revascularization Revascularization of CTOs aims to restore anterograde flow, improve myocardial perfusion, reduce ischemic burden, and enhance left ventricular function and exercise capacity.⁵,⁶ However, functional recovery-a patient-centered endpoint-is not universal, and predictors remain poorly defined.⁷,⁸ Central Research Question After restoring blood flow to a chronically occluded coronary artery, will the myocardium recover its function? This question lies at the heart of clinical decision-making, as not all patients experience functional recovery post-procedure.⁸ Identifying robust predictors of recovery is a clinical priority that can guide patient selection, procedural planning, and postprocedural expectations.

1.3 The Concept of Myocardial Recovery

Functional recovery after revascularization is contingent upon the presence of viable but dysfunctional myocardium, characterized by:

Term Definition Viability The presence of living, metabolically active myocytes that can resume function if reperfused Hibernation Chronic reversible contractile dysfunction due to sustained reduction in resting coronary blood flow Stunning Post-ischemic dysfunction that persists despite restoration of normal perfusion Functional Recovery Objective improvement in LVEF, wall motion, or exercise capacity after revascularization The extent to which each mechanism operates varies among patients and determines the recovery potential-a concept central to this proposal.⁷,⁸ 1.4 The Unifying Concept Functional recovery after CTO revascularization is multifactorial. A comprehensive predictive model must integrate mechanical, biological, and technical domains to accurately identify patients who will benefit most.

2. Motivation and Objectives 2.1 The Clinical Dilemma Challenge Why It Matters CTO affects 15-25% of CAD patients Large, growing population with limited predictive tools Revascularization is increasingly performed Outcomes remain variable, with unpredictable functional recovery Functional recovery is the patient-centered endpoint More meaningful than angiographic success alone Current prediction tools are fragmented No integrated, pre-procedural model exists

2.3 Specific Objectives

Primary Objective:

To develop an integrated predictive model combining stress echocardiography-derived myocardial work indices, inflammatory biomarkers (MHR, sST2, PIIINP), and procedural techniques to predict functional recovery after CTO revascularization.

Secondary Objectives:

1. To investigate the association between procedural technique and functional recovery, with exploration of potential mediation through acute inflammatory response.
2. To determine the independent and relative contributions of each domain (mechanical, biological, technical) to functional recovery .
3. To explore the interaction effect between baseline Monocyte-to-HDL Ratio (MHR) and contractile reserve in predicting functional recovery
4. To compare myocardial work stress echo indices along the inflammatory markers with traditional viability assessment.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with symptomatic and documented CTO confirmed by coronary angiography with TIMI 0 flow lasting ≥3 months Age ≥18 years Referred for percutaneous coronary intervention (PCI) Provision of written informed consent

Exclusion criteria

• Acute myocardial infarction within 7days (as Acute inflammation contaminates biomarkers, within 7 days of an acute MI, sST2, MHR, and PIIINP values will reflect the acute infarction, not the chronic CTO state. the measured inflammatory response to a fresh myocardial injury, not the stable inflammatory milieu of a patient with a chronic total occlusion) and also stress test is contraindicated post-recent MI . Severe valvular heart disease (aortic stenosis with peak velocity ≥4.0 m/s or mean gradient ≥40 mmHg; mitral regurgitation graded severe; or any valvular lesion requiring imminent intervention)- because it independently alters myocardial work indices and is a contraindication to stress echocardiography ) and any significant valvular lesion that may independently affect LV function and alter myocardial stress indices . Contraindications to stress echocardiography Life expectancy <1 year due to non-cardiac comorbidity, as determined by the treating physician(ethical burden on vulnerable patients and for study integrity) Active infection (until clinical resolution or normalization of CRP or a return to the patient's baseline inflammatory state , -2 months post-infection is used in some inflammatory profiling studies- ) Inflammatory disease Rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and similar conditions produce chronically elevated MHR and sST2 Atrial Fibrillation or Significant Arrhythmia (reliable myocardial work analysis cannot be performed without stable sinus rhythm. Hypertrophic Obstructive Cardiomyopathy or Significant LV Outflow Tract Obstruction (Dobutamine stress is contraindicated in HOCM because it can provoke dynamic obstruction and hemodynamic collapse . Additionally, HOCM independently alters myocardial work indices through pressure overload) Severe Renal Insufficiency (eGFR <30 mL/min/1.73m²) sST2 and PIIINP are cleared partly by the kidney. In advanced renal failure, baseline levels are chronically elevated regardless of cardiac status, making ΔsST2 and ΔPIIINP uninterpretable Active Malignancy or Chemotherapy Within 6Months , Both sST2 and MHR are influenced by systemic inflammatory states, and chemotherapy directly alters monocyte counts, HDL levels, and fibrotic turnover Recent Stroke or Acute Neurological Event Within 3 Months sST2 is elevated after ischemic stroke and correlates with neurological deficit severity. MHR is also altered in acute stroke cohorts . Pregnancy (Standard precautionary exclusion)