Single Botox treatment cuts AF for 3 years

 

BOSTON – A single set of four injections with botulinum toxin into neuron-containing cardiac fat pads of patients during open-chest cardiac artery bypass surgery led to a long-term cut in the cumulative incidence of atrial tachyarrhythmias during 3-year follow-up in a pilot, sham-controlled study with 60 patients at two Russian centers.

“Because the favorable reduction of atrial fibrillation [AF] outlasted the anticipated botulinum toxin effects on autonomic nervous system activity, this may represent a form of autonomic reverse remodeling” triggered by just one injection of the paralyzing toxin at each of four intracardiac fat pads, Alexander B. Romanov, MD, said at the annual scientific sessions of the Heart Rhythm Society. Botulinum toxin (BT) blocks neuronal release of acetylcholine, thereby interfering with cholinergic neurotransmission and producing hypothesized neurologic remodeling, explained Dr. Romanov, a researcher at the Meshalkin National Medical Research Center in Novosibirsk, Russia.

The current report of 3-year follow-up follows similarly encouraging results seen after 30 days (J Am Coll Cardiol. 2014 Aug;64[6]:628-9) and 12 months (Circ Arrhythm Electrophysiol. 2015 Dec;8[6]:1334-41) in the same group of 60 patients randomized to receive either the BT injections at four intracardiac fat pads or sham injections during standard coronary artery bypass grafting. The researchers enrolled patients at high risk for atrial tachyarrhythmias based on a history of paroxysmal AF. After 36 months, the primary endpoint of incident atrial tachyarrhythmia occurred in 50% of the 30 sham-control patients and in 23% of those treated with BT, a 64% relative risk reduction in a proportional hazard model that was statistically significant (P = .02). The Kaplan-Meier plot of the primary endpoint over time in each of the two subgroups suggested continued separation of the curves during the third year of follow-up.

The 3-year results also showed statistically significant differences or trends favoring BT injections for several other clinical outcomes. Two deaths and two strokes occurred, all among the control patients. Two patients required a total of three hospitalizations during follow-up in the BT-treated group, compared with 10 patients hospitalized a total of 21 times in the control arm. Clinicians prescribed antiarrhythmic drugs to six of the BT-treated patients and to 15 of the controls.

All patients received an implanted heart rhythm monitor during their bypass surgery, and the researchers measured AF burden – the percentage of time during which AF occurred. After 12 months, 24 months, and 36 months, the AF burden averaged 0.2%, 1.6%, and 1.2%, respectively, in the BT-treated patients and 1.9%, 9.5%, and 6.9% in the sham-control patients.

Mitchel L. Zoler/MDedge News

Based on these promising findings Allergen, a company that markets a BT formulation (Botox) plans to start later in 2018 a randomized trial with about 300 patients to further test the efficacy of BT injections for preventing AF, Dr. Romanov said. He and his associates are also exploring the feasibility and efficacy of injecting BT into cardiac sites via a percutaneous needle to preclude the need for open surgery.

“We don’t know why this works, but it’s a fascinating new approach that is worthy of further study,” commented Kalyanam Shivkumar, MD, professor and director of the Cardiac Arrhythmia Center at the University of California, Los Angeles, and designated discussant for the report.

“This is an extremely exciting study, but it remains inconclusive because how it works is not fully understood,” commented Andrew D. Krahn, MD, professor and chief of cardiology at the University of British Columbia in Vancouver.

mzoler@mdedge.com

 

BOSTON – A single set of four injections with botulinum toxin into neuron-containing cardiac fat pads of patients during open-chest cardiac artery bypass surgery led to a long-term cut in the cumulative incidence of atrial tachyarrhythmias during 3-year follow-up in a pilot, sham-controlled study with 60 patients at two Russian centers.

“Because the favorable reduction of atrial fibrillation [AF] outlasted the anticipated botulinum toxin effects on autonomic nervous system activity, this may represent a form of autonomic reverse remodeling” triggered by just one injection of the paralyzing toxin at each of four intracardiac fat pads, Alexander B. Romanov, MD, said at the annual scientific sessions of the Heart Rhythm Society. Botulinum toxin (BT) blocks neuronal release of acetylcholine, thereby interfering with cholinergic neurotransmission and producing hypothesized neurologic remodeling, explained Dr. Romanov, a researcher at the Meshalkin National Medical Research Center in Novosibirsk, Russia.

The current report of 3-year follow-up follows similarly encouraging results seen after 30 days (J Am Coll Cardiol. 2014 Aug;64[6]:628-9) and 12 months (Circ Arrhythm Electrophysiol. 2015 Dec;8[6]:1334-41) in the same group of 60 patients randomized to receive either the BT injections at four intracardiac fat pads or sham injections during standard coronary artery bypass grafting. The researchers enrolled patients at high risk for atrial tachyarrhythmias based on a history of paroxysmal AF. After 36 months, the primary endpoint of incident atrial tachyarrhythmia occurred in 50% of the 30 sham-control patients and in 23% of those treated with BT, a 64% relative risk reduction in a proportional hazard model that was statistically significant (P = .02). The Kaplan-Meier plot of the primary endpoint over time in each of the two subgroups suggested continued separation of the curves during the third year of follow-up.

The 3-year results also showed statistically significant differences or trends favoring BT injections for several other clinical outcomes. Two deaths and two strokes occurred, all among the control patients. Two patients required a total of three hospitalizations during follow-up in the BT-treated group, compared with 10 patients hospitalized a total of 21 times in the control arm. Clinicians prescribed antiarrhythmic drugs to six of the BT-treated patients and to 15 of the controls.

All patients received an implanted heart rhythm monitor during their bypass surgery, and the researchers measured AF burden – the percentage of time during which AF occurred. After 12 months, 24 months, and 36 months, the AF burden averaged 0.2%, 1.6%, and 1.2%, respectively, in the BT-treated patients and 1.9%, 9.5%, and 6.9% in the sham-control patients.

Mitchel L. Zoler/MDedge News

Based on these promising findings Allergen, a company that markets a BT formulation (Botox) plans to start later in 2018 a randomized trial with about 300 patients to further test the efficacy of BT injections for preventing AF, Dr. Romanov said. He and his associates are also exploring the feasibility and efficacy of injecting BT into cardiac sites via a percutaneous needle to preclude the need for open surgery.

“We don’t know why this works, but it’s a fascinating new approach that is worthy of further study,” commented Kalyanam Shivkumar, MD, professor and director of the Cardiac Arrhythmia Center at the University of California, Los Angeles, and designated discussant for the report.

“This is an extremely exciting study, but it remains inconclusive because how it works is not fully understood,” commented Andrew D. Krahn, MD, professor and chief of cardiology at the University of British Columbia in Vancouver.

mzoler@mdedge.com

 

BOSTON – A single set of four injections with botulinum toxin into neuron-containing cardiac fat pads of patients during open-chest cardiac artery bypass surgery led to a long-term cut in the cumulative incidence of atrial tachyarrhythmias during 3-year follow-up in a pilot, sham-controlled study with 60 patients at two Russian centers.

“Because the favorable reduction of atrial fibrillation [AF] outlasted the anticipated botulinum toxin effects on autonomic nervous system activity, this may represent a form of autonomic reverse remodeling” triggered by just one injection of the paralyzing toxin at each of four intracardiac fat pads, Alexander B. Romanov, MD, said at the annual scientific sessions of the Heart Rhythm Society. Botulinum toxin (BT) blocks neuronal release of acetylcholine, thereby interfering with cholinergic neurotransmission and producing hypothesized neurologic remodeling, explained Dr. Romanov, a researcher at the Meshalkin National Medical Research Center in Novosibirsk, Russia.

The current report of 3-year follow-up follows similarly encouraging results seen after 30 days (J Am Coll Cardiol. 2014 Aug;64[6]:628-9) and 12 months (Circ Arrhythm Electrophysiol. 2015 Dec;8[6]:1334-41) in the same group of 60 patients randomized to receive either the BT injections at four intracardiac fat pads or sham injections during standard coronary artery bypass grafting. The researchers enrolled patients at high risk for atrial tachyarrhythmias based on a history of paroxysmal AF. After 36 months, the primary endpoint of incident atrial tachyarrhythmia occurred in 50% of the 30 sham-control patients and in 23% of those treated with BT, a 64% relative risk reduction in a proportional hazard model that was statistically significant (P = .02). The Kaplan-Meier plot of the primary endpoint over time in each of the two subgroups suggested continued separation of the curves during the third year of follow-up.

The 3-year results also showed statistically significant differences or trends favoring BT injections for several other clinical outcomes. Two deaths and two strokes occurred, all among the control patients. Two patients required a total of three hospitalizations during follow-up in the BT-treated group, compared with 10 patients hospitalized a total of 21 times in the control arm. Clinicians prescribed antiarrhythmic drugs to six of the BT-treated patients and to 15 of the controls.

All patients received an implanted heart rhythm monitor during their bypass surgery, and the researchers measured AF burden – the percentage of time during which AF occurred. After 12 months, 24 months, and 36 months, the AF burden averaged 0.2%, 1.6%, and 1.2%, respectively, in the BT-treated patients and 1.9%, 9.5%, and 6.9% in the sham-control patients.

Mitchel L. Zoler/MDedge News

Based on these promising findings Allergen, a company that markets a BT formulation (Botox) plans to start later in 2018 a randomized trial with about 300 patients to further test the efficacy of BT injections for preventing AF, Dr. Romanov said. He and his associates are also exploring the feasibility and efficacy of injecting BT into cardiac sites via a percutaneous needle to preclude the need for open surgery.

“We don’t know why this works, but it’s a fascinating new approach that is worthy of further study,” commented Kalyanam Shivkumar, MD, professor and director of the Cardiac Arrhythmia Center at the University of California, Los Angeles, and designated discussant for the report.

“This is an extremely exciting study, but it remains inconclusive because how it works is not fully understood,” commented Andrew D. Krahn, MD, professor and chief of cardiology at the University of British Columbia in Vancouver.

mzoler@mdedge.com