Key result
Pheochromocytoma is associated with moderately higher high-frequency HRV and vagal activity versus controls.
Why the study?
Pheochromocytoma can alter cardiovascular activity, and the impact of this catecholamine-producing tumor on heart rate variability parameters needed to be synthesized.
Does pheochromocytoma alter heart rate variability parameters compared to controls?
Meta-Analysis (n=178)
Does pheochromocytoma alter heart rate variability parameters compared to controls?
Effect estimate: ES 0.50 (95% CI 0.04 to 0.96)
p-value: p=0.033
Paradoxically, patients with pheochromocytoma exhibit higher heart rate variability (increased parasympathetic activity), likely due to desensitization of beta-adrenergic receptors from chronic catecholamine over-secretion.
Challenges expected sympathetic dominance on HRV in pheochromocytoma; extends meta-analytic evidence for autonomic adaptation.
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). To conduct a systematic review and meta-analysis on the impact of pheochromocytoma on HRV parameters. PubMed, Cochrane, Embase and Google Scholar were searched until 10th October 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 >50ms of variation), LF (low-frequency) and HF (high-frequency), and LF/HF. 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. 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. • Relying on measures such as rMSSD, HF, and the LF/HF ratio identifies precise and consistent trends between pheochromocytoma patients and control groups, highlighting autonomic adaptation mechanisms. • The unexpected finding of higher HRV in patients with pheochromocytoma is explained by chronic catecholamine over-secretion, leading to desensitization of autonomic receptors. • The importance of HRV as a biomarker in the evaluation of pheochromocytomas could help practitioners monitor patients' cardiovascular health and autonomic function and would improve early detection of the disease.
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Dutheil et al. (2025) conducted a meta-analysis in Pheochromocytoma (n=178). Pheochromocytoma vs. Controls without pheochromocytoma was evaluated on High-frequency (HF) heart rate variability (ES 0.50, 95% CI 0.04 to 0.96, p=0.033). Pheochromocytoma patients exhibited higher vagal activity with higher high-frequency heart rate variability compared to controls (ES 0.50).
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