Can the heart rate be “hacked”?

Our heart does not work in a vacuum – the nervous system tightly controls its rhythm. Under conditions of oxygen deficiency – hypoxia – the body naturally speeds up the heart rate to deliver more oxygen to the tissues. While it is known that the sympathetic nervous system – the part of the autonomic nervous system responsible for "fight or flight" reactions – plays a key role in this process, the influence of the parasympathetic nervous system, responsible for "rest and digest" reactions, has remained unclear until now.

A new study published in the group journal Nature Scientific Reports sheds light on the issue. The article, whose lead author is Dr. Piotr Niewinski, along with Dr. Stanislaw Tubek, Dr. Krzysztof Nowak, and Prof. Piotr Ponikowski, was written in collaboration with a research team from the Institute of Heart Diseases at the Wrocław Medical University and the Jan Mikulicz–Radecki University Clinical Hospital in Wroclaw. The researchers conducted a novel study on the effects of parasympathetic cardioneuroablation (PCNA). This medical procedure reduces the activity of the vagus nerve, which is responsible for slowing down the heart. Their goal was to test the extent to which weakening the influence of the parasympathetic nervous system alters the heart's response to oxygen deprivation.

Study: How do you turn off the heart's "brake"?

The study was conducted on a group of 11 patients who underwent parasympathetic cardiouneuroablation (PCNA) as a treatment for recurrent vasovagal syncope, a condition in which excessive activity of the vagus nerve causes a sudden slowing of the heart rate and a drop in blood pressure, leading to unconsciousness. The vagus nerve is part of the parasympathetic nervous system and acts as a “brake” on the heart – slowing it down and helping to keep the rhythm stable. Its weakening can make the heart beat faster and respond less flexibly to changes in the body.

To assess how the procedure affects the heart's response to oxygen deprivation, hypoxia tests were performed on patients before and after PCNA. Hypoxia is a condition in which the body receives less oxygen, which can lead to an accelerated heart rate and changes in cardiovascular function. Patients inhaled nitrogen as part of the test, which briefly lowered oxygen levels in the blood. During the tests, key parameters such as heart rate, blood pressure, respiratory rate, and blood oxygen saturation levels were monitored to see how the heart adapted to the new conditions.

In addition, after each test, patients were given atropine, which blocks the influence of the vagus nerve on the heart. This allowed the researchers to precisely measure how much the parasympathetic nervous system influences the regulation of heart rhythm before and after the procedure. In this way, the researchers analyzed the heart's response to oxygen deprivation and the effect of PCNA on other mechanisms of cardiovascular regulation.

Special attention was paid to the baroreflex (cBRS) sensitivity, which maintains stable blood pressure. It acts as an automatic regulator—when pressure drops, the heart speeds up, and when it rises, it slows down. Weakening this mechanism can make it difficult for the body to adjust to sudden changes in pressure, such as suddenly standing up from a lying position.

The second key indicator was heart rate variability (HRV), the natural variation in heartbeat intervals. A high HRV indicates a healthy, flexible heart that adapts well to different situations, such as exertion or stress. Low HRV, on the other hand, can signal problems with the nervous and cardiovascular systems, increasing the risk of heart rhythm disorders.

Through this comprehensive approach, the researchers were able to assess how impaired vagus nerve function affects cardiac regulation and whether reduced vagus nerve activity could lead to long–term consequences for patients' health.

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New insights into heart rhythm control

The most important result of the study was the confirmation that the parasympathetic nervous system plays a key role in regulating heart rate under conditions of oxygen deprivation. Until now, researchers have surmised that the primary mechanism responsible for accelerating heart rate in hypoxia is stimulating the sympathetic nervous system, which acts like gas in a car – it increases the heart rate in response to stressful conditions. However, the study's results indicate that weakening the parasympathetic nervous system, which acts like a brake, is equally essential in this process.

After the PCNA procedure, which reduced vagus nerve activity, several significant changes were observed:

The heart responded more weakly to oxygen deprivation. Under normal conditions, when oxygen levels drop, the heart rate naturally speeds up to increase oxygen delivery to the tissues. After PCNA, this effect was much less pronounced, meaning that weakening the parasympathetic nervous system reduced this response.

Heart rate variability (HRV) decreased after PCNA, meaning that the heart became less flexible in responding to changing conditions. The decline in HRV suggests that the heart has lost some of what appears to be an important adaptive capacity.

The sensitivity of the baroreflex (cBRS), the mechanism responsible for maintaining stable blood pressure, was weakened. After the procedure, the ability of this mechanism to adapt rapidly was impaired, but only in terms of the heart rate response.

Interestingly, the maximum heart rate after atropine administration remained unchanged, which means that the sympathetic nervous system – responsible for accelerating the heart – was not significantly modified. In addition, if the sympathetic nervous system was mainly responsible for the heart's response to hypoxia, the PCNA treatment should not have had much effect on this process. Meanwhile, the study results show that the influence of the parasympathetic nervous system is the key factor regulating the heart's response to oxygen deprivation. This finding changes previous assumptions and suggests that the mechanisms controlling heart rhythm are more complex than previously thought.

Could changes in cardiac control be dangerous?

PCNA treatment is a potentially effective treatment for vasovagal syncope. In patients with such episodes of syncope, the procedure can significantly improve quality of life, eliminating the risk of sudden unconsciousness and its potentially dangerous consequences, such as falls or injuries. In addition, PCNA may be an option for people whose syncope does not respond to standard treatments such as lifestyle modification, adequate hydration, or pharmacotherapy.

On the other hand, weakening the vagus nerve's control over the heart carries some risks, especially long–term consequences. The study showed that heart rate variability (HRV) and baroreflex sensitivity (cBRS) decrease after PCNA. HRV is the natural fluctuation in the heart's rhythm, which indicates its ability to adapt to different situations – the greater it is, the better. A decrease in HRV suggests that the heart becomes less flexible and may adapt less well to the work of other organs, such as the lungs (speeding up the heart rate on inspiration and slowing down during expiration). In turn, impaired baroreflex sensitivity (cBRS) means that the body does a worse job regulating blood pressure, although the mechanism described is only one of many elements that control it. Moreover, PCNA is not suitable for all patients with bradycardia or slow heart rate. The procedure only works in cases where excessive vagus nerve activity is responsible for the slowed heart rate rather than structural damage to the cardiac conduction system.

"In elderly patients with diseases such as chronic heart failure, myocarditis, or sinus node disease, the problem is often the heart structure itself rather than the overactivity of the vagus nerve. In such cases, PCNA would not work, and the only effective treatment may be, for example, the implantation of a pacemaker"- Dr. Niewinski points out.

How do you know if a patient is eligible for PCNA? A key test before treatment is the administration of atropine – a substance that blocks the action of the vagus nerve, mimicking the effect of parasympathetic denervation. Suppose the patient's heart rate increases markedly after atropine administration. In that case, the vagus nerve is responsible for slowing the heart rate, and PCNA may be a practical solution. In contrast, the lack of response to atropine suggests that the cause of the problem is damage to the heart itself rather than excessive parasympathetic activity, in which case PCNA would not make sense.

"Failure to respond to atropine would disqualify the patient from PCNA treatment"- Dr. Niewinski explains.

What's next? New questions and future research

The Wroclaw team's findings shed new light on the mechanisms that regulate heart rate under hypoxia. They confirm that the parasympathetic nervous system plays a key role in the heart's response to hypoxia, and the PCNA procedure may be an effective solution for patients suffering from vasovagal syncope. However, as the researchers point out, many questions remain about the long–term consequences of the procedure and its effects on the cardiovascular system.

Is there a way to selectively attenuate the influence of the vagus nerve without negatively affecting HRV and cBRS? This is one of the most critical questions researchers are asking. The optimal solution would be to partially attenuate the activity of the vagus nerve—enough to prevent syncope but not disrupt the physiological regulation of heart rate.

"Thus, it can be seen that, optimally, PCNA should only partially reduce the activity of the vagus nerve so that physiological abnormalities are relatively minor and clinical efficacy is preserved. Our group's subsequent study will answer whether this is the case in reality"- explains Dr. Niewinski.

What are the long–term consequences of PCNA for patients? This is another question that requires further research. Previous reports suggest that some patients may develop long–term heart rate dysregulation as a consequence of impaired vagus nerve function.

"Another article describing the long–term, twelve–month effects of PCNA on the cardiac autonomic system is in review. Isolated publications on the subject suggest chronic persistence of impaired heart rate regulation, for which a properly functioning vagus nerve is essential. On the other hand, however, at the expense of these disorders, patients are free from reflex syncope, which impedes daily functioning and is potentially dangerous"- the researcher adds.

To better understand PCNA's long–term effect, the team of researchers plans further studies that will analyze how the depth of parasympathetic denervation affects the clinical efficacy of the treatment.

"In the next study, we want to show the relationship of the depth of parasympathetic denervation to clinical remote efficacy, that is, to the occurrence of syncope. We also plan to use transvenous vagus nerve stimulation for perioperative evaluation of the effectiveness of denervation"- explains Dr. Niewinski.

One thing is sure—these results show how complex cardiac regulation is and how much we still have to discover in this field. PCNA is a promising treatment method, but its application needs to be fine–tuned to provide patients with maximum benefit with minimum risk. Will it be possible to find the golden mean between this method's effectiveness and safety? Further research by the Wroclaw team may answer key questions and open up new therapeutic possibilities in interventional cardiology.

D. Sikora

FAQ: Can the heart rate be "hacked"?

What is parasympathetic cardioneuroablation (PCNA), and why was it used in this study?

Parasympathetic cardioneuroablation (PCNA) is a procedure that uses a radiofrequency catheter to heat and destroy the plexiform ganglia (clusters of nerve cells) located in the epicardial fatty tissue of the heart. This selectively reduces the influence of the parasympathetic nervous system on the heart. This is a relatively new treatment for conditions such as vasovagal syncope. In this study, researchers used PCNA as a model to understand the physiological consequences of the vagus nerve's reduced effect on heart rate (HR) reactivity to acute hypoxia in humans, providing a unique opportunity to study this relationship without the confounding effects of general parasympathetic blockade with drugs such as atropine.

Did PCNA affect the cardiac sympathetic nervous system?

The study found no evidence that PCNA altered the activity of the cardiac sympathetic nervous system. The peak heart rate achieved after administration of atropine (which blocks the parasympathetic nervous system) was not significantly different before and after the PCNA procedure. This suggests that sympathetic innervation of the sinus node remained unchanged. Moreover, the variability of systolic blood pressure (SBPV), which was previously associated with sympathetic heart rate control, was also unchanged after PCNA.

What was the effect of atropine (a parasympathetic system blocker) on HRV and cBRS before and after PCNA?

Before PCNA, atropine administration significantly reduced all HRV and cBRS indices, mimicking the effects observed after PCNA. However, after PCNA, atropine administration did not significantly reduce these parameters. This suggests that PCNA alone largely abolished the parasympathetic effects on HRV and cBRS, and that the residual effects of atropine administration after PCNA were minimal because the ablation procedure had significantly reduced parasympathetic activity.

What are the limitations of this study and areas for future research?

Several limitations were considered in the study. The study did not use beta–blockers to isolate the sympathetic nervous system response, mainly for safety reasons related to the participants' baseline low heart rates. The study focused on acute hypoxia, so the results may not directly translate to the effects of long–term hypoxia, such as at high altitudes. In addition, no direct invasive measurements of sympathetic activity were made using microneurography. Future studies could investigate the long–term effects of PCNA on autonomic function, including the potential for parasympathetic reinnervation, and further define the risk–benefit profile of this procedure beyond its efficacy in treating syncope, particularly concerning the observed reduction in HRV and cBRS.

How does acute hypoxia typically affect heart rate, and what role does the parasympathetic nervous system play in this response?

Acute hypoxia, a state of reduced oxygen levels, usually induces an increase in heart rate (tachycardia) as a homeostatic mechanism. This study showed that the parasympathetic nervous system plays a significant role in the heart rate response to acute hypoxia. Patients undergoing PCNA, resulting in partial parasympathetic denervation of the sinus node, showed significantly reduced heart rate responsiveness to experimentally induced hypoxia. This reduction was proportional to the degree of parasympathetic denervation of the heart, suggesting that vagus nerve activity determines heart rate during acute oxygen deprivation.

How did the degree of parasympathetic denervation of the heart translate into the observed changes in heart rate reactivity to hypoxia?

The researchers found a significant positive correlation between the degree of cardiac parasympathetic denervation achieved by PCNA and the relative reduction in heart rate reactivity to hypoxia (the slope of the hHR curve). This means that patients with a greater degree of denervation experienced a more significant blunting of the heart rate response to low oxygen levels, further confirming the key role of the parasympathetic nervous system in this physiological reflex.

What are the potential clinical implications of the study's findings on HRV and cBRS after PCNA?

The significant reduction in HRV after PCNA is a noteworthy finding because reduced HRV has been associated with an increased risk of adverse cardiovascular events. Although HRV is considered a biomarker rather than a direct cause, its reduction may reflect adverse autonomic imbalance. Reduced cBRS suggests less effective buffering of blood pressure fluctuations by the heart, which may also have physiological and clinical consequences, such as the potentially impaired ability to compensate for sudden drops in blood pressure. Further studies are needed to fully understand the long–term clinical impact of these changes after PCNA.