Lifestyle choices can play a significant role in preventing heart failure
In Phoenix, a scientist has turned her attention to one of medicine's quieter crises — the slow failure of the human heart — armed with nearly two million dollars from the National Institutes of Health and a question that cuts to the core of preventive medicine: must dilated cardiomyopathy always end in transplantation, or can we learn to interrupt its march? With 6.7 million Americans living under the shadow of heart failure and half of them unlikely to survive five years, Dr. Inna Gladysheva's molecular investigation into the enzymes and pathways that drive cardiac deterioration represents a rare attempt to move medicine upstream — from managing collapse to preventing it.
- Heart failure claims half its patients within five years, yet the only reliable cure remains a transplant — a scarcity that leaves millions with few meaningful options.
- The disease progresses through a cascade of molecular disruptions: proteolytic enzymes degrade critical proteins, destabilizing the body's blood pressure and fluid systems until the heart can no longer keep pace.
- Fluid accumulates in lungs and limbs, breathing becomes labored, function erodes — the body's distress signals arriving long after the damage has taken hold.
- Gladysheva's team is probing whether lifestyle interventions — diet, exercise, behavioral change — can meaningfully slow or redirect this progression, particularly across different ages and sexes.
- The research aims to reframe the clinical horizon: rather than waiting for transplant eligibility, identify molecular targets early enough to prevent symptomatic heart failure from ever fully arriving.
A University of Arizona researcher has received a $1.9 million NIH grant to investigate why dilated cardiomyopathy — a condition in which the heart muscle thins and stretches until it can no longer pump effectively — progresses so reliably toward heart failure, and whether that progression can be interrupted before it becomes irreversible.
The stakes are not abstract. The Heart Failure Society of America estimates that 6.7 million Americans currently live with heart failure, a number expected to reach 8.5 million by 2030. One in four people will develop the condition in their lifetime. Yet the therapeutic options remain sparse — most treatments manage symptoms rather than alter the underlying disease — and cardiac transplantation stands as the only reliable cure.
Dr. Inna Gladysheva, a research professor at the Translational Cardiovascular Research Center in Phoenix, will lead a team examining proteolytic enzymes and their role in disrupting the renin-angiotensin-aldosterone system, the biological pathway governing blood pressure and fluid balance. When this system is thrown into disarray, the consequences become visible: fluid accumulates in the lungs and body, patients struggle to breathe, and functional decline accelerates toward death.
Her research will also explore whether non-pharmaceutical interventions — changes in diet, exercise, and lifestyle — can meaningfully alter the disease's course, and whether those effects vary by sex and age. The broader ambition is a paradigm shift: rather than accepting transplantation as the inevitable endpoint, Gladysheva wants to understand the molecular machinery of progression well enough to intervene years earlier. Collaborators including cardiologist Guy Reed and molecular biologist Sofiyan Saleem helped shape the proposal. The path from molecular discovery to clinical treatment is long, but for millions facing a disease with few good answers, the direction matters enormously.
A researcher at the University of Arizona College of Medicine in Phoenix has received nearly two million dollars from the National Institutes of Health to investigate one of cardiology's most pressing puzzles: why some people's hearts enlarge and weaken in ways that lead inexorably to heart failure, and whether that progression can be slowed or stopped.
The condition is called dilated cardiomyopathy. The heart muscle thins and stretches, losing its ability to pump blood effectively. Once symptomatic heart failure develops—the stage where the heart can no longer meet the body's demands—the prognosis darkens considerably. About half of patients diagnosed with this form of heart failure die within five years. Currently, a heart transplant remains the only reliable cure, a reality that underscores how limited treatment options remain.
Dr. Inna Gladysheva, a research professor in the Department of Internal Medicine and part of the Translational Cardiovascular Research Center, will lead the investigation. Her work will focus on proteolytic enzymes—proteins that break down other proteins—and how their activity in the body contributes to the disease's progression. She'll examine in particular how these enzymes disrupt the renin-angiotensin-aldosterone system, a crucial biological pathway that regulates blood pressure and fluid balance. When this system goes haywire, the cascade of damage accelerates.
One visible sign of this deterioration is edema, the accumulation of fluid in the lungs or throughout the body. Patients experience breathlessness, functional decline, and in severe cases, death. Gladysheva's research will also explore whether non-pharmaceutical interventions—diet, exercise, other lifestyle modifications—can meaningfully alter the disease's trajectory, and whether these effects differ based on a patient's sex and age.
The numbers underscore why this work matters. The Heart Failure Society of America estimates that 6.7 million Americans over age twenty currently live with heart failure. That figure is projected to climb to 8.5 million by 2030. One in four people will develop heart failure at some point in their lifetime. Yet the therapeutic arsenal remains thin. Most current treatments manage symptoms rather than prevent or reverse the underlying damage.
Gladysheva frames her research as an attempt to shift the paradigm. Rather than accepting transplantation as the endpoint, her team wants to understand the molecular mechanisms driving disease progression well enough to intervene earlier—to develop drugs or behavioral strategies that could prevent symptomatic heart failure from developing in people with dilated cardiomyopathy, or slow its advance in those already affected. She emphasizes that lifestyle choices may play a more significant role in prevention than currently recognized, particularly for patients at risk or in early stages of disease.
The grant represents validation of this approach from the nation's premier medical research funder. Gladysheva acknowledges the collaborative effort behind the award, naming colleagues including cardiologist Guy Reed, veterinary researcher Ryan Sullivan, and molecular biologist Sofiyan Saleem, whose combined expertise shaped the research proposal. The work ahead will be long—translating molecular discoveries into clinical treatments typically takes years—but the potential payoff is substantial: better options for millions of Americans facing a disease that currently offers few good ones.
Citas Notables
Our exciting discovery suggests and offers a new paradigm in heart failure management. The long-term project goal is to translate knowledge into novel therapeutic strategies needed to prevent or treat the progression of heart failure.— Dr. Inna Gladysheva, University of Arizona College of Medicine – Phoenix
La Conversación del Hearth Otra perspectiva de la historia
Why does dilated cardiomyopathy lead so reliably to heart failure? Is it inevitable?
It's not quite inevitable, but the disease creates conditions that make progression likely. The heart muscle weakens and stretches, and that triggers a cascade of biological responses—inflammation, hormonal imbalances, fluid retention—that accelerate the damage. The question Gladysheva's work is asking is whether we can interrupt that cascade before it becomes irreversible.
The research focuses on proteolytic enzymes. Why those specifically?
These enzymes are like molecular scissors. They cut proteins apart, and in a healthy heart, that's a controlled process. But in dilated cardiomyopathy, the activity goes unchecked. The enzymes damage the structures that hold the heart together and disrupt the signaling systems that regulate blood pressure and fluid balance. Understanding how to modulate that activity could be the key to slowing disease progression.
You mentioned lifestyle choices might matter. What does that mean practically?
Diet, exercise, stress management—the usual suspects. But the research will examine whether these interventions actually change the molecular pathways driving the disease, not just manage symptoms. And it will look at whether the effect differs between men and women, or younger versus older patients. That specificity is important for real clinical application.
If this research succeeds, what does success look like?
A drug that prevents or delays the onset of symptomatic heart failure in people with dilated cardiomyopathy. Or evidence that certain lifestyle modifications, combined with existing medications, can meaningfully extend the time before transplantation becomes necessary. Right now, transplant is the only real cure. Success means giving patients more options and more time.
Why has this been so hard to solve until now?
Heart failure is complicated. Multiple biological systems are involved, and they interact in ways that aren't fully understood. You need funding, collaborative expertise, and time to work through the mechanisms. This grant gives Gladysheva's team the resources to do that work systematically.