An experimental transcatheter shunt system that moves blood from the left atrium to the right atrium in patients with heart failure provided even greater benefit at 2 years than in the first year, according to 2-year results from ALT-FLOW, a multidisciplinary, single-group, feasibility study.
"Through 2 years, we found clinically meaningful and durable improvements in heart failure symptoms, functional capacity, and quality of life, without any adverse changes in right heart size," said Javed Butler, MD, a distinguished professor of medicine at the University of Mississippi School of Medicine in Jackson.
The study, conducted at 17 participating sites , used the novel and not-yet-approved APTURE transcatheter shunt system (Edwards Lifesciences). The system, which directs blood from the left atrium to the right atrium though the coronary sinus, is an alternative to septal systems that use the interatrial septum to shunt blood.
New Device Challenges Septal Shunts
Previous randomized sham-controlled trials that tested the long-term benefit of septal devices have generated "mixed results," according to Butler, who presented the ALT-FLOW results at the Cardiovascular Research Foundation's Technology and Heart Failure Therapeutics (THT) meeting in Boston. The data were published simultaneously in JACC: Heart Failure.
The new system is "more physiologic" than the multiple septal devices now available, he explained. Advantages of the novel device include a more natural blood flow and preservation of the septum for future interventions. Potential advantages include the protection of right heart function, a reduction in the risk for stroke, and a reduction in the risk for paradoxical embolism.
Patients in ALT-FLOW had to have a left ventricular ejection fraction (LVEF) of > 40%, which led to the enrollment of heart failure patients with midrange ejection fraction or with preserved ejection fraction. Patients had to meet several criteria for adequate hemodynamics, such as a pulmonary capillary wedge pressure of > 15 mm Hg at rest, and had to be on stable guideline-directed medical therapy.
When the 1-year results were presented, data were available on 87 of the 95 patients (92%) enrolled. Now, at 2 years, data are available on 62 of 87 patients (71%).
The longer follow-up not only showed the preservation of gains from baseline identified at 1 year but also modest further improvements.
The most notable change from baseline was the reduction in symptomatic heart failure. At baseline, almost all patients (92.6%) were in New York Heart Association class III heart failure. At 1 year, only 31.8% remained in that class.
At 2 years, only 14.5% of patients being followed were in class III heart failure. Of the remaining study participants, 56.5% were in class II heart failure and 29.0% were in class I heart failure, meaning they had no limitations on ordinary physical activity.
The gains from 1 year to 2 years for most other endpoints were modest but provided additional evidence that patients, on average, were protected from the heart failure deterioration that would have occurred without treatment.
For example, the baseline Kansas City Cardiomyopathy Questionnaire overall summary score climbed from a median of 38.1 at baseline to 63.7 at 1 year (P < .001) and then to 69.8 at 2 years. And the proportion of patients who achieved at least a 15-point increase climbed from 61% at 1 year to 79% at 2 years. These increases were seen across multiple questionnaire domains.
On the 6-minute walk distance functional measure, the mean baseline distance of 247.5 meters climbed to 306.3 meters at 1 year (P = .001) and then to 307.2 meters at 2 years. In 54% of patients, the walk distance increased by at least 32 meters from baseline to 2 years.
In ALT-FLOW, 25.3% of patients had pulmonary vascular disease, defined as a pulmonary vascular resistance of ≥ 2 Wood units. When these patients were compared with those who had a lower resistance, the general performance of the shunt device was shown to be similar and consistent across all outcomes, Butler reported.
No Harm to Right Heart Function
The preservation of functional status at 2 years was not accompanied by any detriment in function or size of the right heart, according to the echocardiographic data Butler presented. The lack of any meaningful change in right ventricular diastolic dimension was observed regardless of initial pulmonary vascular resistance or LVEF.
When assessed by the change in strain of the left atrium or left ventricle, the left heart was also unchanged at 2 years.
At baseline, beta-blockers were being taken by 70.5% of patients. More than half of the patients (56.8%) were taking an angiotensin receptor‒neprilysin inhibitor or an angiotensin inhibitor. However, only 42.1% were taking a mineralocorticoid antagonist, and even fewer (24.8%) were taking a sodium glucose cotransporter-2 (SGLT2) inhibitor.
This is a limitation of this study, according to Robert J. Mentz, MD, chief of the Heart Failure Section at the Duke University School of Medicine in Durham, North Carolina. Although these preliminary data are "promising," it is important to understand the performance of this device relative to medical therapy.
The reason is that the candidates for this "invasive procedure" are likely to have symptomatic HF with midrange ejection fraction or with preserved ejection fraction. Generally, such patients do not achieve adequate control of heart failure despite evidence-based medicines, according to Mentz.
Although the data showing long-term control without any adverse impact on the right side of the heart are encouraging, the randomized sham-controlled trial needed to confirm the ALT-FLOW results will have to show a benefit over optimized medical therapy, particularly in patients with comorbid obesity, Mentz said.
Butler reported financial relationships with more than 50 pharmaceutical and device companies, including Edwards Lifesciences, which provided funding for this trial. Mentz reported financial relationships with Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll.