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Editor's Note: This is Part Three of a three-part series highlighting several of the presentations from the American College of Cardiology’s Annual Scientific Session (ACC.26) that took place in March in New Orleans, Louisiana.
- Click here to read Part One on "The Role of Cardiac Imaging in Clinical Decision-Making"
- Click here to read Part Two on "Advances in Angiography and PCI"
Over the past five years, sodium-glucose co-transporter2 (SGLT2) inhibitors and nonsteroidal mineralocorticoid receptor antagonists (MRAs) have emerged as medication breakthroughs for treating heart failure with preserved ejection fraction (HFpEF). Now, abstracts presented at the American College of Cardiology’s Annual Scientific Session in late March added new evidence on experimental therapies for both HFpEF and an uncommon subtype, combined post- and pre-capillary pulmonary hypertension in patients with HFpEF (CpcPH-HFpEF).
“These trials add a lot of debate and excitement to the fact that we may have additional novel agents coming down the pike to help us with the management and monitoring of HFpEF patients,” says Chonyang Albert, MD, medical director of Left Ventricular Assist Devices (LVAD) and Mechanical Circulatory Support at Robert Wood Johnson University Hospital.
First-in-Class Drug May Improve Outcomes
Historically, no proven therapies existed for CpcPH-HFpEF, a condition associated with significant mortality. The Phase 2 CADENCE trial examined the safety and efficacy of sotatercept, an activin signaling inhibitor designed to reduce abnormal cell proliferation in blood vessel walls.
A total of 164 CpcPH-HFpEF patients were randomized. Groups received sotatercept at 0.3 mg/kg, 0.7 mg/kg, or placebo. Patients taking sotatercept showed improved pulmonary arterial pressure, with a statistically significant reduction in pulmonary vascular resistance. Secondary endpoints showed improved six-minute walking distance, enhanced right-heart function, and a lower rate of clinical events in the sotatercept group.1
“These results suggest that we have a brand-new medication with a novel mechanism of action that seems to show efficacy in a very difficult-to-treat disease,” Dr. Albert says. “I’m really looking forward to seeing where the data goes with sotatercept, and I’m hoping that with a larger, Phase 3 trial, the drug can officially be brought to market.”
Remote Monitoring Could Reduce Hospitalizations
Another encouraging finding came from the IMPEDANCE-HFpEF trial, conducted at a single center in Israel. It tested a non-invasive device that monitors early fluid accumulations in the lungs.
The single-blind trial enrolled 150 patients with HFpEF. Half were randomized to receive lung-impedance-guided care; the other half received standard care. Results showed that patients in the impedance group achieved an 81% reduction of recurrent hospitalization, a 65% lower rate of all-cause death, and an 81% lower rate of heart failure death than the standard-care group.2
“This trial is adding to the body of literature indicating that ambulatory monitoring might help us detect subclinical changes in the intravascular volume that allow clinicians to adjust medications and provide guidance before the patient develops a full-blown heart failure exacerbation,” Dr. Albert says.
“One limitation, however, is that it’s a single-center study in one country, whereas other competitor trials [such as studies investigating CardioMEMS or Cordella] were larger, randomized, multicenter trials,” she adds. “So, we have to be careful in overinterpreting data that comes out of one center, no matter how robust it may be.”
Increased Hospitalizations
While CADENCE and IMPEDANCE showed encouraging results, the SPIRIT-HF trial showed that a steroidal aldosterone blocker, spironolactone, did not significantly reduce hospitalizations or cardiovascular death at 24 months in heart failure patients with preserved or mildly reduced ejection fraction. It also showed a statistically significant increase in total hospitalizations in patients taking spironolactone compared with placebo.3 A double-blind randomized trial, SPIRIT-HF included 730 patients and was conducted at 56 centers in four European countries.
Despite these results, aldosterone blockers remain a proven therapy for heart failure with reduced ejection fraction (HFrEF). “I advise caution in overinterpreting the SPIRIT-HF data,” Dr. Albert says. “I fear the results may dissuade physicians from prescribing this class of medications for HFrEF, where we have a large number of randomized clinical trials that demonstrate the efficacy and relative safety of these medications.”
Looking forward, Dr. Albert expects future research to uncover new approaches to managing HFpEF’s associated comorbidities. “You’ll start to see over the next decade or two that many of the medications used to treat HFpEF will also touch on things like diabetes and obesity,” she says, highlighting the emerging multimodal treatment options for cardiovascular-kidney-metabolic syndrome.
References
1. Gomberg-Maitland M, Tedford RJ, Langleben D, et al. Sotatercept for combined post- and pre-capillary pulmonary hypertension associated with heart failure: Results from the Phase 2, randomized, placebo-controlled CADENCE study. Circulation. Published online March 29. doi:10.1161/CIRCULATIONAHA.126.079918
2. Kleiner-Shochat M. IMPEDANCE-HFpEF: Early noni-nvasive detection of lung fluid reduces death, hospitalization. American College of Cardiology. Published March 29. Accessed April 14. acc.org/latest-in-cardiology/articles/2026/03/25/21/27/sun-1045am-impedance-acc-2026
3. American College of Cardiology. SPIRIT-HF: Does spironolactone benefit patients with HFpEF, HFmrEF? Published March 29. Accessed April 14. acc.org/latest-in-cardiology/articles/2026/03/25/21/27/sun-1045am-spirithf-acc-2026
April 02, 2026 
