Pheochromocytoma and heart rate variability: a systematic review and meta-analysis

Introduction
Pheochromocytoma is a catecholamine-producing tumor, that may alter cardiovascular activity. Conveniently, sympathovagal activity can be measured non-intrusively and pain-free through heart rate variability (HRV).

Objective
To conduct a systematic review and meta-analysis on the impact of pheochromocytoma on HRV parameters.

Methods
PubMed, Cochrane, Embase and Google Scholar were searched until October 10, 2024 for articles reporting HRV parameters in pheochromocytoma patients. Random-effects meta-analysis were conducted on each HRV parameters stratified on pheochromocytoma patients and controls and then comparing these two groups: RR intervals (or Normal-to-Normal intervals-NN), SDNN (Standard Deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR intervals with >50 ms of variation), LF (low-frequency) and HF (high-frequency), and LF/HF.

Results
We included six studies for a total of 178 patients: 94 with pheochromocytoma and 84 controls. Compared to controls, pheochromocytoma patients had higher vagal activity with higher HF (ES = 0.50, 95CI 0.04 to 0.96) and rMSSD (1.22, 0.09 to 2.35), and a tendency for higher pNN50 (1.14, −0.14 to 2.41). The sympathovagal balance tended to be higher in pheochromocytoma patients compared to controls with a tendency for a decreased LF/HF (−0.97, −2.03 to 0.09). Pheochromocytoma patients also tended to have lower RR-intervals than controls (−0.39, −0.86 to 0.07). Sympathetic activity (LF and SDNN) did not differ between pheochromocytoma and controls.

Conclusion
Paradoxically, pheochromocytoma patients have higher HRV. The sympathovagal balance may be explained by a desensitization of beta-adrenergic receptors consecutive to chronic high levels of catecholamine.