TRANSFORM HFrEF Study Aims to Improve HF Outcomes

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Massachusetts General Hospital researchers have partnered with the American College of Cardiology (ACC) to conduct the prospective, randomized TRANSFORM HFrEF study aimed at improving outcomes and treatment for heart failure with reduced ejection fraction (HFrEF).

"The goal is to achieve optimal medical therapy and improve quality of life," says James L. Januzzi, MD, the study's primary investigator and director of the Dennis and Marilyn Barry Fellowship in Cardiology Research at Mass General's Corrigan Minehan Heart Center.

Through the TRANSFORM HFrEF study, Dr. Januzzi's team will redesign the 20-minute visit by providing additional support to patients and clinicians, including MDs, DOs, nurse practitioners and physician assistants. The goal is to emphasize the urgency of achieving optimal doses in guideline-directed medical therapies (GDMT).

Limitations of Current HFrEF Treatments

Over the past two decades, researchers have identified several therapies favorable for heart failure prognosis. Other GDMT, including angiotensin receptor neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, have only added to clinicians' armamentarium. These therapies could potentially lengthen the lives of HFrEF patients by as much as eight years compared to previous therapeutic options.

Despite these advances, heart failure's rising prevalence continues to exact a substantial toll. Patients experience poor outcomes, including decreased function and quality of life, as well as higher hospitalization rates and mortality.

"The five-year mortality risk for HFrEF patients after hospitalization is 50%," says Dr. Januzzi. "There's no other diagnosis in cardiology with that kind of fatality rate, which approaches and exceeds most forms of cancer."

To address this problem, the team is reviewing both clinician-related and patient-related factors.

Clinician-related factors

Dr. Januzzi cites limitations involved with the standard 20-minute follow-up outpatient appointment as a possible impediment. Twenty minutes is the average amount of time nationwide it takes to:

• See the patient
• Collect the history
• Do the physical exam
• Make clinical decisions

"Given its short length and the complexity of some patients' conditions, it makes it much more challenging to address the necessary level of detail," says Dr. Januzzi. "There are often so many things to worry about during this brief encounter that clinicians may think the patient appears perfectly fine and there's no need to titrate therapies."

Dr. Januzzi also says that clinicians may not understand current optimal GDMTs for heart failure. Recent studies suggest that only 1% of eligible HFrEF patients receive GDMT at the target doses specified in current practice guidelines.

"The state-of-the-art continues to evolve. Additionally, there may be concerns about the risks of maximizing therapies to target doses relative to the potential for side effects, such as low blood pressure and worsening kidney function," he says. "This shows we have a clear gap between the knowledge and application of best care. That's where TRANSFORM HFrEF comes in."

Patient-related factors

Polypharmacy is common in patients with HFrEF because they usually have other medical conditions. But taking so many medications may lead to a lack of understanding or resistance to medication increases, changes or additions.

"Patients sometimes have a sense of fear about how and why their therapies need to be changed so frequently," says Dr. Januzzi. "I often tell patients during their first visit not to get used to doses since they will change. We educate them to know how we will get to the target and why they would want to get to the target. The problem is, again, within the bounds of a 20-minute visit, many clinicians don't have the time to do that kind of education."

Redesigning Outpatient Care with TRANSFORM HFrEF

The TRANSFORM HFrEF study will allow Dr. Januzzi's team to redesign the 20-minute visit, provide additional support to patients and the full care team, while emphasizing the urgency of achieving optimal doses in GDMT.

"It's something we've repeatedly seen as possible in clinical trials that fall short in real-world practice," says Dr. Januzzi. "The hope is that prior to entering the exam room, both the clinician and patient will already be aligned about what needs to be done to optimize GDMT."

The six-month trial involves 3,072 participants from around the country. Researchers will randomize participants into an intervention or usual care arm. Patients and clinicians in the intervention arm will receive guidance from the ACC Expert Consensus Decision Pathway for Heart Failure document to understand the importance of optimizing GDMT and how to do it. The goal of these materials, which will also include patient-facing CardioSmart information, is to educate, maximize trust and emphasize the importance of gain sharing.

Investigators will follow participants longitudinally to see how their care evolves. They will compare the two cohorts to determine whether the intervention successfully achieved better medical therapy.

A secondary goal is to evaluate the change in health status between the two study arms using the Kansas City Cardiomyopathy Questionnaire.

"We hypothesize that the intervention will not only improve the GDMT application in heart failure but also improve health status, including quality of life," Dr. Januzzi says.

Amid the COVID-19 pandemic, the study will also include trackable patient encounters that happen virtually since medication adjustments do not always require in-person interactions.

"It emphasizes that in this new world of clinical trial execution, remote patient management takes on even greater emphasis. Those clinical trials that are wired to involve remote visits are destined to succeed in the course of the pandemic, while the more traditional clinical research organization-based trials that require face-to-face visits are going to go slowly until the pandemic has ended."

Optimizing the 20-Minute HFrEF Follow-Up Visit

Study authors believe that increased knowledge about what patients and clinicians need to achieve before entering the exam room can improve efficiency in the 20-minute visit.

"It's almost certain to be a more successful encounter if both the clinician and patient walk into the room knowing what the situation is with respect to GDMT, symptoms and signs," says Dr. Januzzi.

To achieve this goal, they are delivering the logic of the ACC Expert Consensus Decision Pathway document electronically, via a clinical artificial intelligence company that helps to:

• Read the electronic health record of the patient before the visit
• Scan for GDMT adequacy
• Identify gaps in medical therapy
• Report this information to the clinician before the visit

"It really provides a 21st-century approach to care without getting too intrusive," says Dr. Januzzi.

The team also uses an electronic platform to track a patient's health status at home through their completion of the Kansas City Cardiomyopathy Questionnaire. Between visits, the platform disseminates the CardioSmart information to patients.

The CardioSmart materials allow patients in the intervention arm to read up on their medications and future doses. It also enables them to print out a questionnaire they can give to their physician that tells the doctor how they're feeling, what their symptoms are and if there have been changes.

"It catapults us to the point of a decision almost immediately when we walk into the exam room," says Dr. Januzzi.

Diversity and Inclusivity in TRANSFORM HFrEF

Dr. Januzzi emphasizes the importance of focusing on diversity and inclusivity in modern clinical trials. For the TRANSFORM HFrEF study, his team actively sought a participant demographic makeup that reflects the U.S. population in terms of women and underrepresented minorities.

"In prior Mass General Heart Center research efforts, we've achieved this goal in our multicenter studies. For example, the recent PROVE-HF study had one of the highest percentages of African American participants in a cardiology clinical trial performed in North America in recent years," he says.

This focus on diversity extended to TRANSFORM HFrEF's leadership as well. "I've emphasized diversity and inclusion in the assembly of steering committees for clinical trials as well as junior faculty and trainee involvement in clinical trial leadership. The TRANSFORM HFrEF study has an equitable balance of men, women and minorities, along with a healthy number of junior faculty and trainees in leadership," says Dr. Januzzi. "For cardiology clinical trials to continue to evolve in a contemporary fashion, it's critically important to maintain that focus on diversity and inclusion from top to bottom."

Learn more about the Heart Failure and Cardiac Transplant Program

Refer a patient to the Corrigan Minehan Heart Center