Implanting Pacemaker Before Liver Transplant Does Not Lead to Better Outcomes, Study Reveals

Implanting Pacemaker Before Liver Transplant Does Not Lead to Better Outcomes, Study Reveals

Although most patients with familial amyloid polyneuropathy (FAP) who undergo liver transplant will require a pacemaker, implanting the device before the transplant is not beneficial, according to a new study.

The research, “Pacemaker implantation in familial amyloid polyneuropathy: when and for whom?,” was published in the Journal of Interventional Cardiac Electrophysiology.

Cardiac manifestations in patients with FAP are due to dysautonomia — malfunction of the autonomic nervous system — and deposits of the amyloid protein. Because these complications may persist after a liver transplant, which is the standard treatment for symptomatic FAP patients, implanting a pacemaker is important to prevent syncope (loss of consciousness usually due to insufficient blood flow to the brain) and sudden cardiac death.

However, clear guidelines guiding when to perform this procedure in FAP patients undergoing liver transplants are still lacking.

The team from Coimbra Hospital and University Centre (CUMC) and University of Coimbra, in Portugal, addressed this gap by reviewing the data of 258 patients — 54% men, 31 years old at FAP diagnosis and 36 years old at the time of their transplant.

Specifically, the investigators correlated the severity of polyneuropathy, or nerve damage, with the development of cardiac conduction disorders — abnormal conduction of electrical impulses in the heart. They assessed the impact of different timings of pacemaker implants on clinical outcomes.

The patients were divided into three groups: 112 without a pacemaker and who did not develop cardiac conduction disorders during a mean follow-up of 12.2 years; 73 with a pacemaker after liver transplant and conduction disorders; and 73 with a pacemaker before liver transplant regardless of having conduction anomalies. All transplants were done between 1992 and 2012.

All studied patients carried the typical FAP-related mutation in the Portuguese type of FAP (TTR Val30Met mutation), which consists in replacing the amino acid valine with methionine at position 30 in the TTR gene. The most common symptoms at diagnosis were paresthesia and dysesthesia (76%) — usually described as painful, itchy, burning or prickling sensations — followed by gastrointestinal manifestations such as nausea, vomiting and diarrhea (38%), pain in the extremities (23%), fatigue (22%), and weight loss (21%).

The group requiring pacemakers after liver transplant showed greater polyneuropathy severity, as assessed by the Machado-Joseph score, and higher circulating levels of alanine aminotransferase and total bilirubin (which indicate liver damage) — than the patients who never required a pacemaker.

Overall, all-cause mortality was 27%, with a mean time between liver transplant and death of six years. The people who died during follow-up were older at the time of transplant than those who did not (41 vs. 34 years). Only 40% (75 of 190) of patients alive at the end of follow-up did not have a pacemaker implanted.

In the group with cardiac conduction disorders and receiving a pacemaker after liver transplant, the mean time between the two procedures was 8.1 years, “reinforcing the effectiveness of transplantation in mitigating cardiac involvement in FAP,” the team said. The most common reason for pacemaker referral was first degree atrioventricular block (46%), which interrupts the conduction of impulses between the heart’s atria and ventricles.

Mortality was significantly lower when pacemakers were implanted post-transplant compared to pre-transplant (12% vs. 33%). Also, the time between transplant and death was significantly longer in those with a pacemaker after transplant (10.7 years) than in the two other groups — 4.0 years in people without pacemakers and 3.1 years in patients with the devices before transplant.

The data further showed that the mortality rate in the group without pacemakers and cardiac conduction disorders was 33%, mainly due to acute liver rejection or infections.

Overall, the results suggest that “the majority of FAP patients submitted to liver transplantation will need a pacemaker at some time of follow-up,” the scientists wrote. “However, it seems that there is no benefit in “prophylactic” [preventive] cardiac pacing before liver transplantation,” they concluded.

José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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