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CHICAGO – Closure of arteriovenous fistulas used in dialysis patients improved heart function after transition to successful kidney transplantation, according to a small study reported here.
Patients who underwent fistula ligation showed significant reductions in left ventricular mass, volume of all four heart chambers, and NT-proBNP levels (a marker of cardiac stress), said Michael Stokes, MBBS, of the University of Adelaide in Australia.
On the other hand, patients who didn't have the fistula closed in the trial continued to show deleterious remodeling of the heart, Stokes reported in a late-breaker presentation at the American Heart Association's annual Scientific Sessions.
He reported a 14.7% decrease in left ventricular mass – the study's primary endpoint – among patients who underwent fistula ligation compared to patients treated with usual care and left with functioning fistulas (P<0.001).
"Kidney transplantation is the preferred treatment for end stage renal disease with marked improvements in quality of life and survival benefit," Stokes told attendees. "Nevertheless, kidney transplant recipients have a persistently elevated risk of cardiovascular disease with a reported prevalence of 41.6%. Cardiovascular disease accounts for 28%-40% of deaths in patients with a functioning kidney transplant.
"Up to 90% of patients on dialysis have an arteriovenous fistula or arteriovenous graft 2 years after dialysis initiation," he noted. "Most kidney transplant recipients continue to keep this arteriovenous fistula patent after successful transplantation, as little is known about the impact of a persistent, functioning fistula on cardiovascular structure and function in this population. These fistulas may draw up to 10%-20% of cardiac output to maintain a redundant vessel following successful kidney transplantation."
Stokes and colleagues randomized 64 patients to either having the fistula closed or leaving the fistula intact. Ligation was performed in 31 patients of the 33 who were assigned to ligation. The other 31 patients served as controls. One patients died in each group and three in each group were lost to follow-up, leaving 27 patients in each group for evaluation.
Mean patient age was 60, and men represented more than 60% of each group; more than 70% of the patients had high blood pressure. There were no significant differences between the two groups in their demographics.
Fistula closure did not come with a great cost in adverse events, Stokes said. Six of these patients experiences thrombosis which caused pain and redness over the proximal venous segment. The pain and redness resolved with rest and anti-inflammatory medication. Infection of suture lines occurred in two patients, managed with oral antimicrobial therapy. No patients required admission or surgical re-intervention. There were no significant changes in estimated glomerular filtration rate between patients who underwent ligation and controls at follow-up visits.
The designated discussant for the study, Maria Rosa Costanza, MD, medical director of heart failure research for Advocate Health Institute, and of Edward Hospital Center for Advanced Heart Failure in Naperville, Illinois, called the study "an important and novel proof of concept that can support larger randomized clinical trials powered for clinically meaningful outcomes."
Clinical benefit remains to be proven, she suggested, noting that the study endpoints did not include heart failure events, quality-of-life measures, or mortality.
She also noted that the changes in heart mass did occur with changes in glomerular filtration rate. "This is important," she said, "because, as suggested, closure of the arteriovenous fistula in stable renal transplant recipients might worsen renal allograft function."
Costanza said that she wanted to know if transplantation parameters were different in the groups, including the state of organ ischemia, incidence of delayed allograft function, and type of donor (living versus deceased).
"Two-thirds of the population had hypertension, so it would be interesting to know if blood pressure control was similar in this study, and which medications were used to achieve blood pressure control," she said. "It would also be interesting to know which form of immunosuppressive control was used because some of the immunosuppressive drugs themselves may affect cardiovascular structure."
Disclosures
Stokes disclosed no relevant relationships with industry.
Costanzo disclosed relevant relationships with Scios, CHF-Solutions, Vasogen, CHASE Medical, Abbott, Novartis and United Therapeutics.
Primary Source
American Heart Association
Stokes M, et al "Cardiac Remodeling following Ligation of Arteriovenous Fistula in Stable Renal Transplant Recipients: A Randomised Controlled Study" AHA 2018.