Skin sympathetic nerve activity during unprovoked syncope in an ambulatory patient with postural orthostatic tachycardia syndrome

Cardioneuroablation has gained increasing importance in managing syncope. However, there is no data on sympathetic nerve activity (SNA) in ambulatory patients with unprovoked syncope. We performed a prospective study on 41 participants (38±13 years old, 38 women, 2 men, and 1 transgender man) with postural orthostatic tachycardia syndrome (POTS) and at least one episode of syncope or presyncope in their medical history, approved by the Institutional Review Board of the Cedars-Sinai Medical Center to test the hypothesis that large SKNA bursts precede the onset of syncope. All participants underwent 1-5 days of ambulatory recording using a Faros 180 electrocardiogram (ECG) Monitor (Bittium, Oulu, Finland).¹ Participants were instructed to press the marker button and record in diaries whenever they experienced symptoms. The nerve activity was analyzed using LabChart 8 Pro (ADInstruments Inc, Colorado Springs, USA). One-way ANOVA was used to compare multiple groups using IBM SPSS Statistics 24 (SPSS Inc, Chicago, IL, USA). Two-sided p ⩽ .05 was considered significant.

The most recorded symptoms were lightheadedness, nausea, heart palpitations, and dizziness. Only one participant (2.4 %), a 28-year-old woman, reported an episode of syncope (“stood up and collapsed”). She was treated with clonidine, ivabradine, cromolyn sodium, diphenhydramine, famotidine, metoprolol, naloxone, pyridostigmine, and duloxetine at the time. The active standing test showed a maximal 39 beats per minute (bpm) increase in heart rate (HR) and < 10 mmHg change in blood pressure (BP). The plasma norepinephrine level was 110 pg/ml supine, and 341 pg/ml standing. The 24-hour ambulatory BP recording showed an average systolic BP of 112 mmHg and diastolic BP of 77 mmHg with a nocturnal non-dipping pattern. The 2-week ePatch monitor showed a predominant sinus rhythm and HR ranged between 51 to 176 bpm (mean 104 bpm). The overall average SKNA (aSKNA) was 0.90±0.04 μV. Figure 1A shows the recording before, during and after the 1-min episode of syncope. Large SKNA bursts were noted 3 min before syncope (blue arrow) with an aSKNA of 0.82±0.02 μV. The aSKNA progressively increased to 1.31±0.22 μV 1 min before syncope (p<0.001). The HR increased from 61.9±0.7 bpm at 5 min before to 94.3±9.3 bpm (p<0.001) at 1 min before syncope. Before the onset of syncope, there was an abrupt reduction of HR (peak to bottom 28 bpm) with persistent elevation of SKNA (red arrows). The aSKNA progressively declined during syncope with a peak to bottom drop of 0.52 μV. During the 1-min syncope, aSKNA (1.22±0.20 μV, p=0.022) and HR (80.3±3.4 bpm, p<0.001) were significantly lower than 1 min before syncope. HR variability analysis showed that LF/HF was 0.135 5 min before the syncope and increased to 0.517 5 min after the syncope, suggesting a switch from sympathetic to parasympathetic dominance. The patient also reported a presyncopal episode (“nearly fainted getting up”) (Figure 1B). On the contrary, the aSKNA decreased from 1.05±0.15 μV (5 min before) to 0.99±0.06 μV (1 min before) presyncope (p=0.004). The presyncope was associated with an elevated HR (96.3±6.6 bpm, p<0.001) and aSKNA (1.03±0.05 μV, p<0.001) rather than bradycardia and abrupt SKNA withdrawal. LF/HF was 1.056 5 min before and decreased to 0.416 5 min after the presyncope. A limitation is that these results may not be applicable to untreated patients. While syncope is followed by SKNA bursts, most SKNA bursts and HR elevation episodes are not followed by syncope.

Figure.

ECG, SKNA and HR tracings including 5 min before and 5 min after one syncope episode (A) and one presyncope episode (B) in an ambulatory POTS patient.

Many patients with POTS faint occasionally, and the diagnoses of POTS and vasovagal syncope are not mutually exclusive.¹ The relationship between syncope and SNA has been studied with both microneurography and SKNA recordings during the tilt table testing.^{2, 3} Both techniques consistently documented transient surges of SNA followed by sympathetic withdrawal at syncope. In the present study, we confirmed in an ambulatory participant that large SKNA bursts are present before syncope. Because bradycardia occurred when SKNA remains elevated, the most plausible explanation is that the SNA bursts activated the vagal efferents to caused bradycardia. We conclude that this sequence of events supports the hypothesis that syncope is caused by the activation of the vagal efferents and inhibition of the sympathetic efferents.⁴ Cardioneuroablation may prevent syncope by blocking the vagal efferent activity and bradycardia.