A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function
Heart Failure Deaths Are Increasing. New Treatments Could Help.
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Generated by cloudfront (CloudFront) Request ID: z3IRy6tVt6jHObYE0Kwt_3dZpB7v51cJ_7dZo10ImTX4nM4fp8ClHQ==This Weight Loss Drug Reduces Heart Failure Risk
Research reveals Zepbound might transform heart failure treatment in people with obesity, cutting hospitalization rates and improving life quality
A weight loss medication is showing remarkable promise in treating one of America's most serious health conditions. New research reveals that Zepbound, already celebrated for its effectiveness in weight management, might transform how doctors treat heart failure, offering fresh hope to millions affected by this life-threatening condition.
A game-changing discovery for heart healthIn a transformative development for cardiovascular medicine, researchers have found that tirzepatide, marketed as Zepbound, does more than help people lose weight. The medication shows remarkable potential in treating heart failure, particularly in patients whose hearts can still pump blood normally but struggle to fill with blood between beats, a condition known as preserved ejection fraction heart failure.
The science behind the breakthroughHeart failure affects millions of Americans, making everyday activities like climbing stairs or carrying groceries increasingly difficult. The condition develops when the heart cannot pump blood effectively throughout the body, leading to fatigue, breathing problems, and fluid buildup. Traditional treatments often fall short, especially for patients with preserved ejection fraction heart failure, which has long frustrated medical professionals due to limited treatment options.
3 major benefits revealed in the researchEli Lilly's phase three trial brought together 731 participants, all aged 40 and older, focusing specifically on individuals dealing with both obesity and preserved ejection fraction heart failure. The results proved remarkable: patients using Zepbound achieved an average 15% reduction in body weight while showing significant improvements in their heart condition.
Why this matters for millionsHeart failure currently ranks as one of the leading causes of hospitalization in the United States. The condition affects people of all ages but becomes increasingly common as people get older. Traditional treatments often provide limited relief, making new treatment options critically important for public health.
The obesity connectionMedical experts have long recognized the connection between excess weight and heart problems. What makes Zepbound particularly interesting is its dual action: addressing both weight management and heart function simultaneously. This dual benefit could make it an invaluable tool in treating patients who struggle with both conditions.
Looking toward the futureWhile the initial results generate excitement in the medical community, researchers emphasize the need for continued investigation. Future studies will explore how the medication affects diverse patient populations and whether the heart benefits stem directly from the drug or result from the associated weight loss.
What this means for patientsFor people living with heart failure, especially those who also deal with weight issues, Zepbound represents a potential new option in their treatment journey. The medication's ability to address multiple health concerns simultaneously could simplify treatment plans and improve outcomes.
The path forwardMedical professionals anticipate that Zepbound could become an essential part of heart failure treatment, particularly for patients who also have obesity or type 2 diabetes. The medication's demonstrated effectiveness in improving both cardiovascular health and weight management positions it as a valuable tool in the growing arsenal against heart disease.
What experts say about timingThe medical community remains cautiously optimistic as they await publication of the complete study results. Questions about long-term effects, optimal patient selection, and potential combination therapies with existing treatments still need exploration. However, the preliminary findings suggest a significant step forward in heart failure treatment.
Real-world implicationsFor healthcare providers, these findings could influence how they approach treatment for patients with both heart failure and weight management needs. The potential to address multiple health issues with a single medication could streamline treatment plans and improve patient compliance.
Next steps in researchScientists plan to conduct additional studies to understand the full scope of Zepbound's benefits. Key areas of interest include its effectiveness in different patient populations, optimal dosing strategies, and potential long-term effects. This ongoing research will help determine how to best integrate the medication into existing treatment protocols.
The discovery of Zepbound's potential in treating heart failure marks an exciting development in cardiovascular medicine. As research continues and medical professionals learn more about its benefits, this medication could transform how doctors approach heart failure treatment, offering new hope to millions of patients worldwide.
HF Benefits Look Durable In Single-Arm Study Of Coronary Sinus Shunt
BOSTON, MA—Patients with heart failure and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and elevated left atrial pressures appear to derive lasting benefits from a shunt that diverts blood from the left atrium to the coronary sinus, according to 2-year results from the ALT-FLOW early feasibility study.
Improvements in heart failure symptoms, functional capacity, and quality of life that were observed at earlier time points after implantation of the Apture transcatheter shunt system (Edwards Lifesciences) were sustained or increased with additional follow-up, Javed Butler, MD (Baylor Scott & White Research Institute, Dallas, TX), reported last week at THT 2025.
The findings, published simultaneously online in JACC: Heart Failure, were consistent regardless of the presence of pulmonary vascular disease.
Moreover, the positive changes were not accompanied by adverse effects on right heart structure or function, which have been seen in prior trials of shunts in HF, Ryan Tedford, MD (Medical University of South Carolina, Charleston), detailed in a second presentation.
These results are encouraging but come from a single-arm study, making it unclear how they would hold up when compared with a control group. Indeed, two sham-controlled trials of other shunt types that have been completed in recent years, REDUCE LAP-HF II and RELIEVE-HF, have not shown significant improvements in prognosis or symptoms with the devices and indicated, at least in one trial, the potential for harm in some patients.
Commenting on the new ALT-FLOW results for TCTMD, James Fang, MD (University of Utah School of Medicine, Salt Lake City), said it was "quite impressive" to see some of the benefits—particularly the symptomatic improvements—maintained out to 2 years.
That's on top of the lack of significant right ventricular remodeling, "which is always good to see with a shunt," he said. "You always worry a little bit about that."
For him, however, there are remaining questions about whether any of the shunts being evaluated in HF modify the underlying disease or only improve symptoms, Fang said.
"Whether it's disease-modifying is a really important issue," he said, noting that he'd like to see shunting result in a decrease in HF hospitalizations, which are typically tied to congestion. "Whether this is actually going to do that, I just don't know." Still, symptomatic relief is also an important treatment goal, he said, noting that there remains a need for sham-controlled trials of device therapies.
ALT-FLOW Early Feasibility Study
As Butler reminder his audience, the incidence and prevalence of HFmrEF/HFpEF is on the rise, bringing with it a high risk for mortality, hospitalization, and poor quality of life despite the emergence of effective drug therapies.
The central pathophysiologic feature in these patients, he added, is an elevated left atrial pressure, which is associated with worsening symptoms, exertional dyspnea, poor quality of life, and a host of complications like left atrial and right ventricular dysfunction, mitral regurgitation, atrial fibrillation, and pulmonary hypertension.
Numerous interatrial shunts in various stages of development have been designed to create a channel through the septum between the left and right atria to relieve pressure in the left atrium, but have yielded mixed results. The Apture device uses an alternative approach, shifting blood to the right atrium via the coronary sinus, which, according to Butler, has the theoretical advantages of using natural blood flow from the coronary sinus to the right atrium, preserving the interatrial septum for future interventions, and lowering complications.
One year results for the ALT-FLOW early feasibility study, presented last year at THT 2024, were promising. At this year's meeting, Butler focused on primary clinical outcomes at 1 year and changes in functional capacity, quality of life, and echocardiographic findings among the subset of patients who completed 2-year follow-up.
ALT-FLOW, conducted at 17 sites, is a single-arm feasibility study that enrolled 106 patients with chronic HF, an LVEF > 40%, NYHA class II-IV symptoms, elevated BNP or NT-proBNP in the 6 months before enrollment, an elevated pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR) < 5 Wood units. All were on stable guideline-directed medical therapy (GDMT) for HF and comorbidities.
After implantation of the shunt was aborted in 11 patients, there were 95 (mean age 71; 50.5% women) in the treated cohort. Most (92.6%) had NYHA class III symptoms, and 37.9% had been hospitalized for HF in the last year. Mean baseline LVEF was 62.5%. More than 25% of patients had PVR > 2 Wood units, indicative of pulmonary vascular disease. The mean PCWP was 20.1 mm Hg at rest and 35.0 mm Hg when exercising at 20 W.
At 1 year, 4.7% of patients had died, including 2.8% from a cardiovascular cause. Another 2.8% had a stroke (0.9% disabling) and 8.5% were hospitalized for heart failure.
Out to 2 years, the improvement in NYHA class observed at 1 year was enhanced, with 85.5% of patients having class I or II symptoms (up from 68.2% at 1 year and 7.4% at baseline).
A similar trend was seen for the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, which improved from a mean of 38.1 points at baseline to 63.7 points at 1 year and 69.8 points at 2 years. At the latest time point, 89% of patients reported an improvement of at least 5 points, 86% at least 10 points, and 79% at least 15 points. These changes occurred across each of the components of the KCCQ—overall summary score, clinical summary score, and total symptom score.
For functional capacity, mean 6-minute walk distance improved by 6 months, with the gain sustained out to 2 years. The mean distance was 247.5 m at baseline and 307.2 m at 2 years.
All these results were consistent regardless of whether patients had pulmonary vascular disease at baseline.
Tedford's presentation provided more detail about the impact of shunting on right heart echocardiographic parameters, showing that there were no adverse changes in size, function, or strain. The lack of a detrimental effect could be due to preservation of natural flow patterns with a left atrium-to-coronary sinus shunt device, he said.
'Impressive' Results, With Caveats
For Fang, there are limitations of the data to consider, pointing to the single-arm design and to the fact that 2-year data were available for only 62 patients.
In addition, the increase in KCCQ scores—which ranged from a mean of 24.6 points for the clinical summary score to 31.3 points for the overall summary score—was almost too large to believe, he said. With that in mind, there is a need for sham-controlled trials of device therapies to confirm the symptomatic benefits and any impacts on clinical outcomes, Fang indicated.
And that's on the way for the Apture shunt system. The ongoing ALT-FLOW II trial is randomizing patients with symptomatic HF despite stable GDMT to shunting or a sham procedure on a background of GDMT, with outcomes that focus on hemodynamic changes.
For any of the investigational shunt systems, it will be critical to identify the right patient population for each one, Fang said. "That's really where this needs to go, is to figure out who are the patients that are going to get lasting and significant benefit on top of GDMT," he said.
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