Of the heart’s four valves, the aortic valve is the one most commonly replaced. The Food and Drug Administration recently announced approval of transcatheter aortic valve replacement, or TAVR, for low-risk surgical patients. TAVR is now a viable alternative to open heart surgery for all patients with severe, symptomatic aortic valve stenosis. Increasingly, research is driving a shift to TAVR, and initiatives at the Froedtert & the Medical College of Wisconsin health network are helping to push the boundaries of TAVR application even further.

TAVR is a minimally invasive procedure in which surgeons guide a new prosthetic valve to the diseased aortic valve, usually using a transfemoral approach. Once the new valve is in position, it expands to press the native valve aside and take over its function.

First performed in 2002, TAVR was initially used as a “last resort” procedure for patients with severe aortic stenosis who were too high a risk for open-heart surgery. Recent trials have demonstrated its equivalence, if not superiority, to surgical aortic valve replacement (SAVR). Compared to SAVR, TAVR is associated with lower risks of mortality, stroke, atrial fibrillation and major bleeding.

The Froedtert & MCW health network is a leading resource for TAVR and other groundbreaking transcatheter procedures. Our program offers patients a critical base of experience backed by knowledge gained from conducting clinical research. Directing the multidisciplinary team within the health network is renowned interventionalist Michael Salinger, MD, who has been an investigator on the clinical trials of TAVR that have led to broader utilization.

Two new clinical trials of TAVR are now enrolling patients at Froedtert & MCW Froedtert Hospital, the only Wisconsin site for these studies. The cardiac team welcomes referrals and offers referring physicians and their patients every available option, from current protocols to clinical trials.

Early TAVR Trial

Objective: Evaluation of TAVR compared to surveillance for patients with asymptomatic severe aortic stenosis.

Background: For symptomatic patients, the treatment of choice is surgery to replace the aortic valve. But for asymptomatic patients, the treatment pathway is less clear.

“The traditional edict was to not do anything, in part, because the only option had been open-heart surgery,” said Peter Mason, MD, MPH, interventional cardiologist and MCW faculty member. “Even with the lowest risk patients there is 1-3% mortality within 30 days.”

But clinical surveillance of asymptomatic patients presents its own set of challenges.

“Among the problems that can occur are the risk of sudden cardiac death, syncope and stroke,” Dr. Mason said. “Patients may develop heart failure. Historically, it was thought that the heart muscle tolerates aortic stenosis, but recent evidence suggests that some patients develop fibrosis and heart muscle weakening. In these patients, valve replacement does not necessarily result in recovery of heart muscle function.”

The Early TAVR Trial will assess TAVR for asymptomatic patients. “The trial will help determine if earlier intervention, in this case with TAVR and its lower procedural risks, will be associated with better clinical outcomes,” said Dr. Mason, the primary site investigator. “Although recent trials have been extremely favorable, the Food and Drug Administration has not yet approved TAVR for patients considered low risk for surgery, defined as a predicted risk of 30-day mortality from SAVR of less than 3%.”

Patients in the Early TAVR study will be randomized 1:1 to receive either TAVR or clinical surveillance.

“The primary endpoint will be to compare the composite of death or stroke and the prevention of cardiac-related hospitalization over two years,” Dr. Mason said. “It will also look at quality of life, left ventricular performance and the onset of things like atrial fibrillation and stroke.”

Inclusion criteria:

  • 65 years of age or older
  • Severe aortic stenosis defined by echocardiogram
  • Asymptomatic, determined both by history and a modified treadmill stress test
  • LV ejection fraction greater than or equal to 50%
  • Society of Thoracic Surgeons (STS) risk score < 10

Exclusion criteria: Factors that rule out candidates include the presence of high-risk markers on a modified stress test. “Patients who experience an abnormal heart rhythm, drop in blood pressure or abnormal heart muscle response to exercise will be excluded,” Dr. Mason said. A complete listing of inclusion and exclusion criteria is available at clinicaltrials.gov.

Dr. Mason said the results of the study will benefit physicians and patients and have the potential to dramatically alter our understanding of and treatment approach to patients with severe asymptomatic aortic stenosis.

“Knowing what to do now can be tricky,” he said. “A provider might have an 85-year-old patient with severe aortic stenosis but no symptoms. Should that patient undergo an invasive therapy with its associated risks or wait until symptoms progress and their general health condition becomes much more complicated? That is the question this trial is trying to answer.”

TAVR Unload Trial

Objective: To determine the safety and efficacy of TAVR via a transfemoral approach in heart failure patients with moderate stenosis, as compared with optimal heart failure therapy.

Background: Treatment guidelines recommend medical therapy rather than surgery for these patients.

“Combine heart failure with reduced ejection fraction and open-heart surgery to replace the valve, and you describe increased surgical risk,” said Michael Salinger, MD, medical director of structural heart disease and MCW faculty member. “We traditionally wouldn’t operate on that valve unless the stenosis is severe.”

Favorable results of recent TAVR studies, however, have given impetus to investigating TAVR for additional indications.

“We theorized that in people who have heart failure, using TAVR to unload that resistance from the impaired left ventricle would result in fewer symptoms, less hospitalization, improved quality of life and maybe even an extended life span,” Dr. Salinger said. He is the primary site investigator for the study.

The trial will build on what physicians already know about TAVR. “We don’t need the heart-lung machine; we don’t have to stop the heart as with surgery; we don’t have a large wound that requires healing like surgery; and, therefore, we think it is potentially beneficial to replace the valve using this lower-risk technology,” Dr. Salinger said.

Participants in the study will be randomized 1:1 to receive either TAVR with optimal heart failure therapy or optimal heart failure therapy.

Inclusion criteria:

  • Moderate aortic stenosis, demonstrated by a mean aortic gradient between 20mmHg and 40mmHg and aortic valve area of >1.0 cm2 and < 1.5 cm2
  • Left ventricular ejection fraction of <50% and >20%
  • New York Heart Association Class II or greater heart failure

Exclusion criteria:

  • Ejection fraction <20%
  • Hospitalization for acute heart failure within two weeks prior to randomization
  • Biventricular pacemaker implantation within three months prior to randomization
  • Bypass surgery within three months prior to randomization
  • Previous aortic valve replacement

A complete listing of inclusion and exclusion criteria is available at clinicaltrials.gov.

Presently, the outlook for heart failure patients with aortic stenosis is poor.

“If the patient doesn’t die from heart failure, they will progress to severe aortic stenosis in five years,” Dr. Salinger said. “But by that time, left ventricular function may have deteriorated to the point where the patient no longer benefits from replacing that valve. Other than transplantation and left ventricular assist, they are short of options.”

The results of the TAVR Unload trial could change that prognosis.

“This study will allow us to consider TAVR in a new context that it would never have been considered before,” Dr. Salinger said. “The trial benefit is that we may confirm a new treatment therapy, namely TAVR, for patients living with heart failure and only moderate aortic stenosis.”

For Our Referring Physicians:

Academic advantage of clinical trials

The Froedtert & MCW health network gives patients and their referring physicians a distinct advantage.

Contact our physician liaison team for more information about our heart and vascular programs, clinical trials or if you would be interested in meeting with any of the heart and vascular team members.

 

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