Quantitative Assessment of Hypertrophic Obstructive Cardiomyopathy With Intraoperative Three-dimensional Transesophageal Echocardiography Under Provocative Dobutamine Stress Test

The objectives of this study are to determine if the left ventricle outflow tract (LVOT) gradients may be reproduced with dobutamine (DBT) provocation test in obstructive HCM patients under general anesthesia and to analyze the change in anatomic LVOT area and pressure gradients (PG) before and after septal myectomy.

If the DBT stress test can reproduce preoperative gradients in HCM patients during septal myectomy surgery, surgeons will have the opportunity to assess the quality of the surgical procedure depending on the obtained gradients with DBT stress test after surgery when gradients can't be reproduced during general anesthesia after myectomy, and decide if further myectomy is required, saving a re-operation on the patient in the future.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertrophic Obstructive Cardiomyopathy
• Intervention / Treatment: Drug: Pre and post-CPB Drug: Dobutamine Hydrochloride; Drug: Post-CPB Drug: Dobutamine Hydrochloride

Detailed Description

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. Echocardiography is the noninvasive method of choice for the evaluation of morphologic and functional abnormalities in HCM. It is of paramount importance to distinguish between obstructive or non-obstructive HCM, based on the presence or absence of left ventricle outflow tract (LVOT) gradient using continuous wave Doppler (CWD), under resting and/or provocable conditions. HCM can then be divided into three different subgroups. When the gradient at rest is ≥ 30 mmHg the HCM is considered obstructive (HOCM); when the gradient is <30 mmHg at rest but ≥ 30 mmHg with provocation, the HCM is considered latent obstructive, and finally, non-obstructive occurs when the gradient is < 30mmHg at rest or with provocation.

The gold standard technique to treat symptomatic HOCM is the surgical transaortic septal myectomy, when the resting gradient or the provocable gradient is ≥50 mmHg. Hemodynamic conditions may change and lead to worsening or improvement in LVOT obstruction during general anesthesia. LVOT gradients during surgery should be measured under reproducible conditions possibly mimicking preoperative hemodynamics.

Dobutamine is a well-known inotropic agent, capable to induce sub-aortic gradients in HOCM. The development of a dynamic LVOT gradient during this test is a pharmacological phenomenon with no clinical significance, not been associated with increased frequency of chest pain, shortness of breath or ischemic wall motion abnormalities, because obstruction resolves after termination of dobutamine (DBT) infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Azad Mashari, MD; Phone Number: 5164 (416) 340-4800; Email: azad.mashari@uhn.ca
• Study Contact Backup: Name: Jo Carroll; Phone Number: 3243 416 340-4800; Email: jo.carroll@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HOCM refractory to medical treatment with symptoms like syncope, angina or NYHA functional classes III and IV, with a resting gradient or provocable gradient equal or greater than 50 mmHg, requiring surgical intervention.
2. Absence of other cardiac or systemic diseases capable of producing hypertrophy.
3. Sinus rhythm.

Exclusion Criteria:

1. Patient refusal.
2. Patient unable to give consent.
3. TEE contraindication.
4. Different rhythm than sinus.
5. Other systemic diseases capable of producing hypertrophy.
6. Severe Aortic or coronary artery pathology.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative Transesophageal Echocardiogram (TEE) PG under anesthesia <50mmHg (Group A); Pre-cardiopulmonary bypass (CPB) (pre-myectomy) echocardiographic parameters: PG under DBT stress test at 5, 10, 15 and 20 mcg/kg/min or until a PG ≥ 50mmHg is achieved, will be recorded.; Post-CPB (post-myectomy) echocardiographic parameters: PG at DBT peak dose (DBT-pd) will be recorded. If LVOT PG post myectomy are >16 mmHg, the surgeon will be advised, for surgical management considerations.	Drug: Pre and post-CPB Drug: Dobutamine Hydrochloride; Pre-CPB provocation test with DBT stress test will be started (starting at 5 mcg/kg/min, increasing every 3 min, to 10, 15 and 20 mcg/kg/min) until a PG ≥ 50mmHg is achieved (DBT peak dose). The DBT peak dose (DBT-pd) will be recorded.; Post-CPB provocation test at the DBT-pd achieved preoperatively.; Other Names: Transthoracic or 2D Echocardiogram; Transesophageal Echocardiogram (TEE)
Experimental: Preoperative PG under anesthesia ≥ 50mmHg (Group B); Pre-cardiopulmonary bypass (CPB) (pre-myectomy) echocardiographic parameters: PG without DBT stress test will be recorded.; Post-CPB (post-myectomy) echocardiographic parameters: PG at 5, 10, 15, 20 mcg/kg/min DBT stress test or until the postoperative provocable PG is >16 mmHg will be recorded.	Drug: Post-CPB Drug: Dobutamine Hydrochloride; Pre-CPB no intervention will be required.; Post-CPB provocation test with DBT stress test will be started (starting at 5 mcg/kg/min, increasing every 3 min, to 10, 15 and 20 mcg/kg/min) or until postoperative provocable PG is >16 mmHg.; Other Names: Transthoracic or 2D Echocardiogram; Transesophageal Echocardiogram (TEE)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analyze if TEE immediate post-myectomy LVOT gradients, may be reproduced with provocation dobutamine test in HOCM patients, when compared to TTE LVOT gradients performed within 6 months post-myectomy, to prove septal myectomy efficacy.	The preoperative gradients obtained by TTE, with and without stress test, within 6 months pre-myectomy, will be compared with the intraoperative TEE pre-myectomy gradients at baseline (before and after DBT stress test). The post-myectomy TEE gradients (before and after DBT stress test), will be compared with the follow up TTE gradients with and without stress test, performed within 6 months post-myectomy, to assess short term outcomes.	Pre-operative up to 6 months, Immediate Intra-operative Pre-myectomy, Immediate Intra-operative Post-myectomy and Post-operative up to 6 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Jacobo Moreno Garijo, MD, Sunnybrook Health Science Centre; Principal Investigator: Azad Mashari, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Transesophageal Echocardiography; Dobutamine Stress test
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Hypertrophy; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Adrenergic beta-Agonists; Sympathomimetics; Adrenergic beta-1 Receptor Agonists; Dobutamine
• Other Study ID Numbers: 16-5412

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No