Results presented at the American Heart Association Scientific Sessions show that a new device designed to treat diastolic heart failure is safe and effective. The first patient in the randomised, blinded study was enrolled at The Ohio State University Ross Heart Hospital, which also enrolled the most patients in the trial.
Diastolic heart failure (DHF) occurs when the heart muscle becomes stiff and doesn't relax enough to allow blood to flow from the lungs into the heart. This causes blood to back up in the lower left chamber, then the upper left chamber and into the lungs, causing shortness of breath.
"The therapies we use for people with systolic heart failure don't work as well for people with DHF. For decades, we've only been able to manage the symptoms of DHF with diuretics," said Dr Rami Kahwash, an advanced heart failure cardiologist and director of the Heart and Vascular Research Organisation at Ohio State Ross Heart Hospital.
Kahwash and Dr Scott Lilly, an interventional cardiologist and director of the Structural Heart Disease Programme at Ohio State, were part of the Phase II study that evaluated a dime-size implant intended to relieve the high pressure created by blood backing up from the heart into the lungs.
During a heart catheterisation, doctors inserted the tiny, inter-atrial shunt device in an opening they created between the upper left and right chambers. This diverts some of the blood from the high pressure left atrial chamber to the low pressure right atrial chamber, much like a detour around a traffic jam.
The study randomised 44 DHF patients at multiple centres nationwide. Participants received either the treatment device or a sham procedure. After one month, patients were evaluated by comparing pulmonary capillary wedge pressure (PCWP) readings during right heart catheterisation exercise. Elevated PCWP readings indicate failure of the left ventricle.
Researchers reported that the inter-atrial shunt device reduced PCWP readings by 3.5 mmHg, compared to a reduction of 0.5 mmHg in the control group.
"This device represents a novel therapy for diastolic heart failure, a condition characterised by lifestyle-limiting breathlessness, and one in which traditional heart failure therapies have not proven effective. If the initial experience is substantiated through ongoing clinical trials, this inter-atrial shunt device may be an opportunity to improve quality of life and exercise capacity for patients that currently have few other options," Lilly said.
Risk factors for DHF include high blood pressure, diabetes, obesity and age. Kahwash said it's estimated that within the next five years, DHF will account for more than half of all heart failure cases, and be responsible for more hospital admissions than systolic heart failure.
Background: In non-randomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), less symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and mid-range or preserved ejection fraction (EF ≥ 40%). We conducted the first randomized, sham-controlled trial to evaluate the IASD in HF with EF ≥ 40%.
Methods: REDUCE LAP-HF I was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, EF ≥ 40%, exercise PCWP ≥ 25 mmHg, and PCWP-right atrial pressure gradient ≥ 5 mmHg. Participants were randomized (1:1) to the IASD vs. a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness endpoint was exercise PCWP at 1 month. The primary safety endpoint was major adverse cardiac, cerebrovascular, and renal events (MACCRE) at 1 month. PCWP during exercise was compared between treatment groups using a mixed effects repeated measures model analysis of covariance that included data from all available stages of exercise.
Results: A total of 94 patients were enrolled, of which n=44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared to sham-control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mmHg in the treatment group vs. 0.5±5.0 mmHg in the control group (P=0.14). There were no peri-procedural or 1-month MACCRE in the IASD group and 1 event (worsening renal function) in the control group (P=1.0).
Conclusions: In patients with HF and EF ≥ 40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation.
Ted Feldman, Laura Mauri, Rami Kahwash, Sheldon Litwin, Mark J Ricciardi, Pim van der Harst, Martin Penicka, Peter S Fail, David M Kaye, Mark C Petrie, Anupam Basuray, Scott L Hummel, Rhondalyn Forde-McLean, Christopher D Nielsen, Scott Lilly, Joseph M Massaro, Daniel Burkhoff, Sanjiv J Shah