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A series of papers published in JACC: Heart Failure provide new findings from the EMPOROR-Preserve trial and several other reports that could benefit the management and treatment of patients with heart failure (HF), specifically those with HF with preserve ejection fraction (HFpEF). Additionally, an expert commentary provides insights into subgroups and special populations in HF clinics.

In EMPOROR-Preserve, original research from João Pedro Ferreira, MD; Milton Packer, MD, FACC; and Javed Butler, MBBS, FACC, et al., reveals patients with HF with mildly reduced ejection fraction (HFmrEF) or HFpEF who had higher serum magnesium levels had lower risk of primary outcomes events if receiving empagliflozin (10 mg/daily) compared with those receiving placebo.

The study randomized nearly 6,000 patients to either empagliflozin or placebo, with lab results available at baseline, weeks 4, 12, 32 and 52 and then every 24 weeks thereafter for a median follow-up of 26 months. The primary outcome was a composite of cardiovascular death or HF hospitalization.

Overall results found that patients receiving placebo experienced a higher risk of primary outcome events with higher magnesium levels, while empagliflozin was associated with a greater reduction of primary outcome events at higher baseline magnesium levels. Researchers also noted that patients with higher magnesium levels were older, had lower estimated glomerular filtration rate, and higher prevalence of atrial fibrillation, while patients with lower serum magnesium had diabetes and more frequently used thiazide-type diuretic agents.

According to the authors: “The role of magnesium in HFmrEF/HFpEF should be investigated further, particularly how the use of SGLT2 inhibitors may increase magnesium levels and how this influences the function of cardiomyocytes, endothelial cells, and autophagic flux.”

In a related editorial comment, Wendy McCallum, MD, et al., highlight that “one of the key messages” from EMPOROR-Preserved is the fact “there was no suggestion of harm with randomization to SGLT2 inhibitor irrespective of baseline magnesium level.” They write that “Ferreira et al., have generated an interesting hypothesis that SGLT2 inhibitors are associated with a differing degree of cardiovascular benefit depending on the baseline magnesium level” and suggest that “future studies to evaluate the role of magnesium and change in magnesium in relation to SGLT2 inhibitor treatment among patients with HFrEF and with HFmrEF/HFpEF are needed.”

Three separate “brief reports” explored other areas of HFpEF management. In one, authors Yu Kang, MD, et al., assessed whether left ventricular (LV) end-diastolic dimension (LVEDD) is a prognostic metric in HFpEF. Their findings suggest yes, with results showing a “showing a U-shaped relationship with mortality” at one-year post-discharge. According to the authors, patients with LVEDD beyond 45 to 59 mm had increased risks of death and distinct clinical characteristics. “This concept of phenotyping HFpEF by LV remodeling could be considered in future clinical practice and research,” they write.

In another report, Silav Zeid, MSc, et al., shared the results of the MyoMobile Trial, which found that an app-based adaptive digital coaching intervention increased daily step count in patients with HFpEF compared with standard of care or physical activity tracking alone. The findings “support integrating digital coaching into routine HFpEF care and warrant future studies to explore long-term effectiveness, broader implementation and potential influences on functional capacity and clinical outcomes,” they said.

In a third brief report, Oluwapeyibomi I. Runsewe, MD, et al., assessed whether use of retinal optical coherence tomography angiography (OCTA) could capture early microvascular changes in HFpEF that are associated with cardio-renal dysfunction. Their results found that retinal OCTA imaging is feasible “in identifying retinal microvascular dysfunction in the form of lower vessel densities (especially for the SCP on 3 × 3 mm angiograms) as a distinct phenotype of HFpEF associated with greater cardiorenal impairment,” and they suggest that “further investigations are warranted to establish the proposed thresholds of retinal OCTA metrics that can noninvasively identify patients with HFpEF and microvascular dysfunction.”

Outside of HFpEF treatment, “leading edge commentary” from Vanessa Blumer, MD, FACC; Biykem Bozkurt, MD, PhD, FACC; and Marvin A. Konstam, MD, FACC, et al., offers an update from the Heart Failure Collaboratory and the Heart Failure Collaboratory Academic Research Consortium Expert Consensus Panel on “consensus definitions and considerations to better characterize subgroups and special populations, supporting more precise, relevant, and patient-centered trial design.”

“In the evolving landscape of HF management, the identification and analysis of subgroups and special populations within clinical trials are crucial for enhancing clinical decision-making, guiding further research, and understanding heterogeneity in study outcomes,” the authors write. “…These efforts aim to improve the evaluation of therapeutic interventions, inform regulatory decision-making, and advance personalized care across the spectrum of HF.”

Specifically, the statement calls on policymakers to address “the root causes of environmental stressors” and adopt stricter air quality and noise standards, phase out fossil fuels and regulate toxic chemicals. It also highlights several health system adaptation and resilience measures, including implementation of public awareness campaigns, health care workforce training and retention strategies, data sharing and interoperability, dedicated funding for health system adaptation and crisis response, investment in telemedicine and integrated care models, and more.

“Research has shown the negative health impacts of pollution, noise, rising temperatures and other environmental stressors,” says ACC President Christopher M. Kramer, MD, FACC. “The time for action on addressing the impact of the environment on cardiovascular health is now and essential to reducing the burden of cardiovascular disease around the world.”