Structural Heart Disease Clinical Trials — A Patient's Guide

What is structural heart disease?

Structural heart disease covers problems with the physical structures of the heart — the valves, walls, and chambers — as opposed to coronary artery disease (blocked arteries), arrhythmias (electrical problems), or cardiomyopathies (muscle problems). The main categories most patients fall into:

• Aortic valve disease. The aortic valve sits between the left ventricle and the aorta. Aortic stenosis (AS) is when the valve narrows and stops opening fully — most often caused by age-related calcification. Aortic regurgitation is when the valve does not close fully and blood leaks backward.
• Mitral valve disease. The mitral valve sits between the left atrium and the left ventricle. Mitral regurgitation (MR) — the valve leaking backward — is the most common form, either from the valve itself (degenerative MR) or from the heart enlarging and pulling the valve apart (functional MR). Mitral stenosis — narrowing of the valve — is less common in the U.S. and is usually a late effect of rheumatic heart disease.
• Tricuspid valve disease. The tricuspid valve sits between the right atrium and the right ventricle. Tricuspid regurgitation is increasingly recognized as a serious problem on its own, often associated with right-sided heart enlargement and atrial fibrillation.
• Congenital heart disease in adults. Defects you were born with that are now being managed in adulthood — atrial septal defect (ASD), ventricular septal defect (VSD), patent foramen ovale (PFO), and others. PFO closure has become a focused field of its own, with specific indications around stroke and migraine in selected patients.
• Hypertrophic cardiomyopathy (HCM). Some classifications include HCM under structural heart disease, especially when the question is whether to perform septal reduction therapy (alcohol septal ablation or surgical myectomy) to relieve obstruction.

The defining feature of this field: treatment is highly anatomic. The exact shape, size, and condition of the valve or chamber drive what is possible.

What structural heart trials are testing in 2026

Structural heart is one of the most active device-trial spaces in cardiovascular medicine. Several directions at once:

• TAVR refinements. Transcatheter aortic valve replacement (TAVR) is no longer experimental for high-risk patients — it is standard. The active research questions in 2026 are about newer-generation devices, valve-in-valve procedures (placing a TAVR valve inside a previously placed surgical or transcatheter valve that is failing), and TAVR in younger patients with longer expected remaining lifespan, where valve durability matters most.
• Transcatheter mitral repair and replacement. This is arguably the most active structural heart space in 2026. Edge-to-edge repair (clip-based devices), annular reduction, chordal repair, and full transcatheter mitral valve replacement (TMVR) systems are all in active pivotal trials. Trials enroll specific MR anatomies and severity levels.
• Transcatheter tricuspid intervention. Multiple device families are in pivotal trials for severe tricuspid regurgitation, including edge-to-edge clip repair and orthotopic and heterotopic transcatheter tricuspid valve replacement.
• Devices for hypertrophic cardiomyopathy. New septal reduction therapies — both transcatheter and surgical — are in trials to relieve obstruction in patients who do not respond well to medication.
• PFO closure for specific stroke (and in some programs, migraine) populations, where the question is which subgroups truly benefit.
• LAA closure. Left atrial appendage closure devices for patients with atrial fibrillation who cannot tolerate long-term blood thinners. Several next-generation devices are in pivotal trials.

A trial is not a guess. By the time a structural heart device reaches a pivotal trial, it has already gone through earlier safety testing in selected patients. The trial is asking a more specific question: in real-world patients with this exact anatomy and severity, does this device achieve its intended result, and is the procedural risk reasonable?

Who might be eligible

Structural heart trial eligibility is more anatomy-driven than other cardiovascular trials. Common requirements:

• Severity criteria. Severe symptomatic aortic stenosis (often defined as mean gradient ≥40 mmHg, peak velocity ≥4 m/s, valve area ≤1.0 cm² with symptoms) for TAVR-related trials. Severe MR or severe tricuspid regurgitation by transthoracic and transesophageal echo for valve-repair trials.
• Specific anatomic features. Each device is designed for a specific anatomy. Mitral clip trials require leaflet length and gap measurements; TMVR systems require annular size ranges; TAVR-in-TAVR requires a known prior valve type and size. The anatomic match is checked on detailed imaging.
• Heart Team evaluation. Most structural heart trials require a multidisciplinary Heart Team evaluation — interventional cardiologist, cardiothoracic surgeon, imaging cardiologist, and often heart failure cardiologist — before enrollment. This is not optional. It is how the trial confirms that the procedure is appropriate, that surgery has been considered, and that you understand the alternatives.
• Stable other comorbidities. Coronary disease addressed (or judged not to need addressing first), diabetes and kidney disease reasonably controlled, no active major non-cardiac illness expected to limit life expectancy below the trial's follow-up window.
• Ability to commit to follow-up. Structural heart trials require detailed imaging at multiple time points over months to years.

You may be excluded for things like very poor kidney function (a problem because cardiac CT and angiography use contrast dye), active infection, recent stroke, severe lung disease, or anatomy that does not match the device. None of these are personal — they are study-design decisions made to keep results clear and participants safe.

What participation involves

Structural heart trials test transcatheter procedures, so the structure is different from a medication-only trial.

Screening (1-3 hours)

You meet the trial team. The Principal Investigator and the Heart Team review your case with you. Screening focuses heavily on detailed imaging review:

• Transthoracic echocardiogram (TTE) — to confirm severity and basic anatomy
• Transesophageal echocardiogram (TEE) — for detailed valve and chamber views, almost always required for valve trials
• Cardiac CT — for annular sizing, vascular access planning (femoral artery size and calcification), and 3D anatomy
• Cardiac MRI in selected cases, especially HCM, congenital, and some mitral and tricuspid evaluations

Plus a focused history, vital signs, ECG, blood draw, and a full review of medications and allergies — including any history of contrast allergy.

You go through informed consent: a detailed document explaining what the trial is studying, what the procedure involves, the known risks (procedural, vascular, valve-related, and device-specific), and your right to leave at any time. (For a section-by-section walkthrough, see our consent-form reading guide.)

Heart Team evaluation

A formal multidisciplinary discussion of your case. The Heart Team reviews your imaging, weighs the trial against standard surgery and standard transcatheter options, and confirms the recommendation. You and your family are part of that conversation.

Pre-procedure visit

Final imaging review, medication adjustments (some blood thinners may be paused or started), pre-procedure labs, anesthesia evaluation, and instructions for the day of the procedure.

The procedure

Most modern structural heart trials test transcatheter procedures — the device is delivered through a catheter inserted in the leg (femoral artery or vein) or, less commonly, through a small chest incision (transapical or transaxillary access). Procedures typically run 1-4 hours, are performed in a hybrid OR or cath lab under general anesthesia or deep sedation depending on the protocol, and most patients stay in the hospital 1-3 nights afterward.

Post-procedure follow-up

Follow-up is structured and image-heavy:

• 30 days (1 month) — clinic visit, ECG, echo, vascular access check
• 6 months — clinic visit, repeat echo, quality-of-life assessment
• 12 months — clinic visit, repeat echo, often with additional imaging per protocol
• Annual visits for several more years — most pivotal structural heart trials follow patients for 5 years or longer to assess valve durability, repeat-intervention rates, and survival

Between visits, phone check-ins are common, especially in the first weeks after the procedure.

What you might gain

Patients have different reasons for considering a structural heart trial. Common ones:

• Access to a newer-generation device that is not yet available outside research — sometimes a device specifically designed for an anatomy that current approved devices do not handle well.
• Care from a Heart Team at a high-volume center with structured imaging review and multidisciplinary input.
• Detailed long-term follow-up with serial echo, imaging, and quality-of-life tracking that routine post-procedure care does not always provide.
• Potential procedural benefit if the device works as designed.

We want to be honest here: a structural heart procedure may help you, may not relieve symptoms as much as hoped, or in some cases may have complications. No one — not the Heart Team, not the trial team, not the device manufacturer — can promise benefit. That is exactly why the trial is being done: to find out.

What the risks are

Structural heart trials carry the standard risks of transcatheter cardiac procedures plus device-specific risks. The consent form covers all of these in detail. The most common categories:

• Procedural risks. Vascular access complications (bleeding, hematoma, vessel injury), valve-related complications (paravalvular leak, valve malposition or embolization), conduction system damage requiring a permanent pacemaker, stroke risk during the procedure, and kidney function decline from contrast exposure.
• Device-specific risks. Each investigational device has its own profile — for example, leaflet capture issues with clip-based mitral repair, or specific deployment risks with a new TMVR system. The consent form lists known device risks.
• Randomization to a comparison treatment. Many structural heart trials randomize between the investigational device and a standard alternative — which may be standard TAVR, surgical valve replacement, surgical repair, or optimized medical therapy. You may not get the investigational device.
• Time commitment. Several follow-up visits with detailed imaging over years.
• Intensive safety monitoring. Structural heart trials run independent Data Safety Monitoring Boards (DSMBs) on accelerated cadences — sometimes reviewing data after every several patients early on. This is a feature, not a flaw: it is how serious safety signals get caught quickly.

You can withdraw at any time, for any reason, without it affecting your future medical care.

How to find out if you are eligible

We want to be straightforward with you: structural heart trial enrollment is more centralized than other cardiovascular trial types. Most pivotal structural heart trials run at high-volume structural heart centers with established Heart Teams that perform many of these procedures every week. Amavita Research is not currently running active procedural structural heart trials at our site. Trial portfolios change over time — call us for the current snapshot.

The most effective path for a patient considering a structural heart trial:

1. Talk to your cardiologist first. Your cardiologist knows your imaging and your history and can flag obvious trial fits or refer you to a structural heart center.
2. Search ClinicalTrials.gov for active trials that match your specific condition (severe AS, severe MR, severe TR, PFO, HCM) and your geography.
3. Call Amavita Research at (786) 703-5941. Even though we do not currently run procedural structural heart trials at our site, our consultative subspecialty lead, Dr. William W. O'Neill, MD, FACC, has decades of structural heart intervention experience and can help orient you to the field. We can also tell you which sites in South Florida are currently enrolling structural heart trials.

When you call, please be ready to share: your most recent echo report (severity numbers if you have them), any cardiac CT or MRI reports, your current medications, and a brief history of prior cardiac procedures or surgeries.

A note on Dr. William W. O'Neill, MD, FACC

Dr. William W. O'Neill, MD, FACC is a recognized pioneer in structural heart intervention in the United States. He performed the first TAVR procedure in the U.S., served as National Principal Investigator on the Edwards PARTNER, Protect II, and Protect IV trials, and founded the National Cardiogenic Shock Initiative. He provides consultative subspecialty leadership for Amavita Research even though primary structural heart procedural work and active procedural trial enrollment happen at higher-volume structural heart centers (including the Center for Structural Heart Disease at Henry Ford Hospital, where he serves as Medical Director).

If you are reaching out about a possible structural heart trial, mentioning his involvement helps us route your inquiry appropriately.

Questions worth asking before you join a structural heart trial

The Heart Team welcomes these questions. If yours is not on the list, ask anyway.

• What does the Heart Team think of my anatomy and trial fit? This is the single most important question and the one that should shape the recommendation.
• What is the chance I will be randomized to the investigational device versus surgical valve replacement, standard TAVR, or medical therapy? This is set by the trial design and the team can tell you.
• How much experience does the operator and the center have with this specific device? Operator and site experience matter in structural heart procedures. The team should be transparent.
• What is the trial's pacemaker rate, paravalvular leak rate, and stroke rate so far, where reported? Many pivotal trials have interim safety data that the team can share at a high level.
• What is the expected lifespan of the device, and what happens if it fails later? Especially relevant for younger patients considering TAVR or TMVR. The team should explain valve-in-valve options.
• How will my regular cardiologist be kept in the loop? With your permission, the Heart Team and trial site send updates and study data to your cardiologist so your care stays coordinated.
• What recovery should I expect? Recovery time varies by access route and procedure — most transcatheter patients are walking within a day or two, with activity restrictions for several weeks.

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About the author: Amavita Research is a cardiovascular clinical trial site in North Miami Beach, FL embedded inside amavita Heart and Vascular Health®. Dr. William W. O'Neill, MD, FACC provides consultative subspecialty leadership in structural heart disease. We don't currently run active procedural structural heart trials at our site, but we can help orient patients to the field. Call (786) 703-5941.