The +40bpm Rule for POTS in Kids is Questionable

New Research

Boris, J. R., Sniatynski, M. J., Bernadzikowski, T. & Kristal, B. S. Comparison of paediatric patients evaluated for postural orthostatic tachycardia syndrome with and without tachycardia. Cardiology in the Young 34, 2132–2141 (2024).
https://doi.org/10.1017/s1047951124025526

• Published on 13 September 2024
• Retrospective Study
• 729 POTS diagnoses aged between 12-18
• Evidence for Diagnosis
• Researchers from East coast USA
• Funding in part by a grant from Standing Up to POTS, Inc. The first author has consulted for CSL Behring.

Headlines

• There is no significant difference in the number of symptoms experienced by 12-18 year-olds with POTS when classified with either a >30bpm or a >40bpm supine-to-standing heart rate increase threshold.
• Using a "tachycardia" threshold, defined in this study as >100bpm within 10 mins of standing, also fails to associate significantly with the breadth of symptom burden.
• The top 5 of 28 symptoms reported at diagnosis were dizziness, headache, fatigue, brain fog and breathing problems with activity.
• Most symptoms were uncorrelated, but photophobia and hyperacusis (i.e. light and sound sensitivity) were commonly seen together.
• Assessing significance of many outcomes at once increases the chance of observing a rare event, e.g. many patients in one group just happen to have headaches (or any particular symptom) for reasons unrelated to their heart rate status. This study used a Bonferroni correction to account for this.

Review

This is an interesting examination of the significance of heart rate thresholds in POTS diagnosis. Using a statistical tweak called Bonferroni correction the authors showed that the number of symptoms reported by patients was not significantly associated with either a +40bpm threshold in supine-to-standing heart rate (compared to +30bpm), nor a "tachycardia" threshold defined as >100bpm within 10 minutes of standing.

These conclusions hinge on the use of Bonferroni-corrected significance thresholds, which are more stringent than the typical and much abused p-value < 0.05 significance cut off. Extra rigour is necessary because the study looks at 28 symptoms, comparing the frequency of each of them between groups of POTS patients; this increases the chance of a rare event, e.g. nearly all of the patients in one group having a particular symptom, like nausea for example, for reasons unrelated to their heart rate status. In particular, the authors specify a "family-wise" probability of false positives at no more than 5% (like the usual "p < 0.05") and split the risk evenly over all 28 symptoms in the "family", giving a significance threshold for any symptom of p < 0.0018.

There were apparent associations in the number of reported symptoms with higher heart rate thresholds, and the severity of reported symptoms was not assessed so couldn't be analysed. In fact, many of the symptom counts were associated with higher heart rate thresholds in a way that would be significant if the Bonferroni correction was not made. It would make sense that patients with increased heart rate abnormalities have more symptoms, and perhaps worse symptoms, but according to this study the extra requirement for kids (+40bpm instead of +30) is not "significantly" associated with the number of reported symptoms. Is it time to adjust the clinical guidance?

The damage done by missed diagnoses in POTS is well-known to patients, as are the benefits of diagnosis--validation, understanding, a sense of direction, not to mention treatment. This study puts forward a convincing argument that considering a young person's clinical picture as a whole, rather than sticking rigidly to increased heart-rate thresholds, is justifiable.

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