Experts from the Duke Clinical Research Institute (DCRI) presented the latest research and provided expert insights at the annual meeting of the Heart Failure Association of the European Society of Cardiology, May 17-20 in Belgrade, Serbia.
DCRI experts presented during 11 different sessions, including three late-breaking science sessions. Presentations covered a wide array of topics, including inflammation and obesity, the latest on safe medication dosing, clinician communication skills, gene therapy, the future of heart failure research, and more.
Heart failure (HF) is classified as a pandemic with an estimated 64.3 million cases worldwide and increasing prevalence. The Heart Failure Congress is the world's leading event covering the entire spectrum of heart failure, from prevention to diagnosis and treatment.
Study Suggests Dosing of Heart Failure Medication Can be Safely Simplified
On Saturday, May 17, DCRI faculty member Stephen Greene, MD, presented research on how simpler dosing of a heart failure medication can be safely simplified to improve patient outcomes.
An estimated 32 million people globally have heart failure with reduced ejection fraction (HFrEF), a condition where the lower left chamber of the heart does a poor job of pumping blood to the rest of the body.
While there are approved medications for the condition, not all providers escalate patient doses to target levels, increasing the risk of adverse events, hospitalizations, and death.
The research, which will be published in the European Journal of Heart Failure, found patients could safely start vericiguat (a medication for HFrEF) at a dose of 5 mg instead of the conventional 2.5 mg starting dose, streamlining the process to reach target dosing from three steps to two. The study was funded by Bayer AG and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Both companies are makers of vericiguat.
“In real-world practice, most patients never achieve the target doses of recommended heart failure medications,” Greene said. “Despite clinic visit after clinic visit, medication changes are relatively rare. If titration of heart failure medications is rare in clinical practice, then it stands to reason that reducing the number of titration steps would give our patients a better chance to ultimately achieve target dosing.”
The study enrolled 106 patients across seven countries who started the 5 mg dose of vericiguat over the course of two weeks. The researchers compared the safety and tolerability of the higher dose group with those of study participants receiving the current dosing standard. The study found safety measures for both groups to be comparable, with more than nine out of 10 patients safely tolerating initiation of vericiguat at the higher 5 mg starting dose.
“I think simplicity is the key when we talk about the implementation of heart failure medications in clinical practice,” Greene said.
Comparing Supine and Upright Positions: Pulmonary Capillary Wedge Pressure Measures at Rest and during Exercise
Measurements commonly used for diagnosing and managing many heart conditions can vary based on whether they are taken while a patient is lying down or seated upright, according to study results presented by DCRI co-chief fellow Veraprapas “Mark” Kittipibul, MD, on Saturday, May 17.
Kittipibul presented his research on how body position affects pulmonary capillary wedge pressure (PCWP), an indirect measure of left atrial pressure. The measurement is used to diagnose and manage various cardiopulmonary conditions.
Certain features of PCWP waveform during right heart catheterization (RHC), like the amplitude of the V wave, are thought to reflect underlying left atrial myopathy, or severe mitral regurgitation. However, little is known about how testing positions influence PCWP measures.
In a prospective multinational study, Kittipibul compared PCWP measures while participants were lying on their back and while upright, at rest, and during exercise.
Patients exercised on a stationary bike while clinicians monitored PCWP. The study used a "supright" protocol, which combined submaximal supine bicycle ergometry (patients pedaling while lying down) with maximal upright bicycle ergometry (patients pedaling while seated upright), alongside breath-by-breath oxygen analysis.
The results showed that PCWP values, including ePCWP and V wave amplitude, were consistently lower in the upright versus the supine position.
“Many patients no longer exhibited significant V waves with reduced cardiac preload due to gravitational pull in the upright position,” Kittipubul explained. “This suggests that V waves, particularly in the supine position, appear to be a predominantly preload-dependent phenomenon rather than a reflection of a stiff left atrium alone.”
He emphasized the need for further research to better understand the clinical significance of persistent V waves at rest and during exercise in the upright position.
Positive Interim Data from First-in-Human Gene Therapy Trial for HFpEF
On Sunday, May 18, DCRI’s Marat Fudim, MD, MHS, presented positive interim data from the first-in-human gene therapy trial for heart failure as part of a late-breaking clinical trials session.
The presentation highlighted interim data from the Medera-funded MUSIC-HFpEF trial, which is evaluating a novel gene therapy called SRD-002 for treating heart failure with preserved ejection fraction (HFpEF), where the heart pumps normally but is too stiff to fill properly.
The presentation highlighted data from the ongoing trial, which, as of the cutoff date, has treated five patients in Cohort A with a low dose of 3x1013 viral genomes (vg) per patient and one patient in Cohort B at a dose of 4.5x1013 vg per patient.
With follow-up ranging from 4 to 16 months, no gene therapy-related serious adverse events were reported. Four out of five patients in the low-dose group have shown improvements in New York Heart Association (NYHA) heart failure classification at six months, with improvements in a 6-minute walk test, and stabilization or reduction in NT-Pro-BNP and high-sensitivity troponin, which are biomarkers of heart stress and damage.
The enrollment of patients at the higher dose of 4.5x1013 vg per patient is ongoing.
“HFpEF represents a significant unmet medical need, affecting approximately half of all heart failure patients worldwide with limited disease-modifying therapeutic options,” Fudim said. “These early results are encouraging and suggest that SRD-002 may offer a potentially transformative approach for patients with HFpEF by directly addressing the underlying pathophysiology of impaired myocardial relaxation.”
“With our therapeutic dosages optimized by our bioengineered human mini-heart HFpEF models – approximately 100-fold less than that of IV infusion – we are pleased with the safety profile and early clinical signals observed in the MUSIC-HFpEF trial to date,” said Ronald Li, PhD, CEO and co-founder of Medera. “This first-in-human gene therapy approach represents an important step forward in our mission to develop innovative therapies for cardiovascular diseases with limited treatment options.”