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.