Comparison of Squat-to-Stand Maneuver With Amyl Nitrite, Valsalva, and Exercise Stress Echocardiography in Inducing Latent Left Ventricular Outflow Obstruction in Hypertrophic Cardiomyopathy

The purpose of this study is to assess the effectiveness of squat-to-stand maneuver in eliciting left ventricular outflow gradients in patients with Hypertrophic Cardiomyopathy (HCM) compared to Valsalva, amyl nitrite inhalation, and exercise stress echocardiogram (ESE).

Study Overview

• Status: Withdrawn
• Conditions: Hypertrophic Cardiomyopathy; Cardiomyopathy, Hypertrophic; Hypertrophic Obstructive Cardiomyopathy
• Intervention / Treatment: Other: Squat-to-stand maneuver; Drug: Amyl nitrite inhalation; Other: Valsalva

Detailed Description

Left ventricular hypertrophy and abnormal ventricular configuration result in dynamic left ventricular outflow obstruction in ~75% of HCM patients, which is associated with increased cardiac morbidity and mortality. However, the dynamic nature of the gradient can make obstruction difficult to identify. Provocative maneuvers such as Valsalva maneuver, administration of amyl nitrite, and ESE are currently used to assess for obstruction.

A shortage of amyl nitrite beginning in December 2018 spurred a search for alternative provocative maneuvers. Beginning in February 2019, the Mayo Clinic echocardiography laboratory began utilizing a squat-to-stand maneuver as an alternative to amyl nitrite inhalation. Anecdotally, the squat-to-stand maneuver, which decreases both preload and afterload, has been successful in provoking latent left ventricular outflow obstruction. A retrospective study (Peng et al, in progress) studying 119 patients who performed the squat-to-stand maneuver between February and September 2019 demonstrated squat-to-stand to be a more robust provocative maneuver than the Valsalva maneuver for identifying severe dynamic left ventricular obstruction with Doppler echocardiography. Squat-to-stand elicited latent obstruction in a greater proportion of the study participants and higher average gradients. It also demonstrated the potential to alter clinical management - six patients had severe obstruction only with squat-to-stand (otherwise would not have been diagnosed) and subsequently underwent septal reduction surgery.

The recent return of amyl nitrite to the echocardiography laboratory creates an opportunity for direct comparison with squat-to-stand, particularly regarding cost savings and diagnostic performance. The primary purpose of this study is to evaluate the efficacy and degree of provocation of left ventricular outflow gradients by the squat-to-stand maneuver compared to amyl nitrite inhalation in patients with HCM undergoing echocardiography. Squat-to-stand will also be compared with other provocation methods, including Valsalva maneuver, which should be performed on every patient going on to squat-to-stand, and ESE when available. Validating this novel provocative maneuver can broaden the toolbox of techniques used to elicit left ventricular outflow gradients and improve clinical evaluation and management of symptomatic HCM patients.

• Study Type: Interventional
• Phase: Not Applicable

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:

• Adults ≥ 18 y/o referred for an outpatient echocardiogram.
• Clinical diagnosis of Hypertrophic Cardiomyopathy (HCM).
• Both amyl nitrite inhalation and squat-to-stand maneuver performed during echocardiogram.

Exclusion Criteria:

• Patients < 18 at the time of echocardiogram.
• Studies without documented provocative maneuvers.
• Patients with resting obstruction (MIG > 50 mmHg).
• Patients unable to undergo the squat-to-stand as protocolled based because of physical limitations.
• Patient with contraindications to amyl nitrite administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypertrophic Cardiomyopathy; Subjects with a documented diagnosis of hypertrophic cardiomyopathy (HCM) will have an echocardiogram at rest followed by an echocardiogram with Valsalva maneuver as part of regular care. If these tests show no severe obstruction, subjects will continue with both squat-to-stand and amyl nitrite.

Other: Squat-to-stand maneuver; Subjects will squat for 5 seconds and then stand. The squat-to-stand exercise will be done up to 10 times, and then immediately undergo echocardiographic imaging.; Drug: Amyl nitrite inhalation; Subjects will inhale amyl nitrite prior to undergoing echocardiographic imaging. This is administered according to current laboratory protocol and is part of standard of care. This is an FDA-regulated drug that will be used as a control and will not be studied experimentally.; Other: Valsalva; Subjects will undergo echocardiographic imaging while performing the Valsalva maneuver. This is according to current laboratory protocol and is part of standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe provokable obstruction	Percentage of patients with provokable obstruction (rest gradient < 30 mmHg AND gradient w/ maneuver ≥ 30 mmHg) by provocation technique	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal instantaneous gradient	Maximal instantaneous gradient (MIG) by provocation technique measured in mm Hg	Baseline
Completion of squat-to-stand maneuver	Percentage of patients unable to complete a squat-to-stand maneuver	Baseline

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Jeffrey Geske, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: May 23, 2021
• First Submitted That Met QC Criteria: May 23, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 24, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: echocardiography; hypertrophic cardiomyopathy; squat to stand maneuver; amyl nitrite; valsalva; exercise stress echocardiography; left ventricular outflow tract obstruction; maximal instantaneous gradient; latent obstruction; dynamic obstruction; squat-to-stand
• 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; Ventricular Outflow Obstruction; Vasodilator Agents; Amyl Nitrite
• Other Study ID Numbers: 21-003194

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