Persistently Elevated Neuropeptide Y, a Sympathetic Neurotransmitter, is Found to be Associated with Ventricular Arrhythmias in Patients with Myocardial Infarction

The sympathetic drive leading to the release of arrhythmogenic agents after myocardial infarction (MI) is the target of pharmacologic treatment to reduce the mortality associated with post-MI arrhythmias. Beta-blockers, so far, are the only primary prevention antiarrhythmic drugs that decrease the mortality following MI.  However, ventricular arrhythmias still complicate up to 10% of the cases despite sufficient beta-blockade. Additionally, MI has been associated with the release of non-catecholaminergic co-transmitters such as neuropeptide Y (NPY). This cardiac sympathetic co-transmitter can affect calcium electrophysiology of the cardiomyocytes and trigger arrhythmic events.

The new study by Dr. Kalla and his colleagues hypothesized that NPY is the pro-arrhythmic agent after an MI. To evaluate their hypothesis, they monitored 78 patients with ST-elevation MI  treated with primary percutaneous coronary intervention (PPCI) for the development of ventricular arrhythmias. Peripheral venous blood sampling was done at the time of intervention to assess the NPY level. To compare, they also measured the NPY level of peripheral venous blood in 12 candidates of elective angiography of similar age and gender, who had normal coronary arteries.

Ventricular arrhythmias occurred in 7% of the STEMI patients within 48 hours. Their venous NPY level has observed to be significantly (P < 0.05) higher compared to control patients. The author also suggested that an NPY level of 27.3 pg/mL has a sensitivity of 0.83 and a specificity of 0.71 for ventricular arrhythmias threshold. To further evaluate their hypothesis regarding the arrhythmogenic effect of sympathetic-induced NPY release, they experimented with an animal model. Through their rat model experiment, Dr. Kalla demonstrated that despite maximal beta-blockade with metoprolol, prolonged stimulation of the sympathetic system caused an enormous increase in NPY level and subsequent decrease in ventricular arrhythmias threshold. Interestingly, NPY, antagonized by Y1 receptor antagonist BIBO3304, prevented these effects.

The authors added, ” In patients presenting with STEMI treated with PPCI, NPY levels are associated with an increased incidence of ventricular arrhythmia in the immediate postinfarct period, independent of classical risk factors, such as late presentation, larger infarct size, and prior beta-blocker usage.” The author concluded that sympathetic-induced release of NPY is associated with post-MI arrhythmia and drugs reversing its effect work along with beta-blockers as a new anti-arrhythmic therapy.