Abstract:Aim To investigate the association between heart rate variability (HRV) and the risk of major adverse cardiovascular events (MACE) in elderly female with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM), and to evaluate the clinical value of HRV for prognostic stratification in this population. Methods A retrospective cohort study was conducted. A total of 103 elderly female patients with HFpEF complicated by T2DM who were hospitalized in the Affiliated Hospital of Qingdao University from September 1,9 to September 1,2 were enrolled. Baseline clinical data were collected at initial assessment, including demographic characteristics, laboratory results, echocardiographic parameters, and 24-hour Holter-derived HRV indices. Patients were followed for 1 year and divided into the observation group(MACE group) and the control group(non-MACE group) according to the occurrence of MACE. Baseline characteristics were compared between the two groups. Variables with P＜0.1 in univariable analysis were entered into least absolute shrinkage and selection operator (LASSO) regression for feature selection, followed by multivariable Cox proportional hazards regression to identify independent factors associated with MACE. Kaplan-Meier curves were constructed to estimate event-free survival, and between-group differences were evaluated using the Log-rank test. Results Compared with the control group, patients were older and had a higher prevalence of prior atrial fibrillation in the observation group (P＜0.05). The levels of N-terminal pro-B-type natriuretic peptide(NT-proBNP), the ratio of peak early diastolic mitral inflow velocity to early diastolic mitral annular velocity(E/e′), and left atrial volume index (LAVI) were higher in the observation group(all P＜0.05), whereas multiple HRV indices including standard deviation of all normal-to-normal R-R intervals (SDNN), root mean square of successive differences between normal-to-normal R-R intervals (RMSSD), percentage of successive normal-to-normal R-R intervals differing by more than 50 ms (pNN50), high-frequency power (HF), low-frequency power (LF), and very low-frequency power (VLF) were significantly lower (all P＜0.05). In addition, the use of β-blockers and dapagliflozin was less frequent in the observation group (P＜0.05). LASSO-Cox regression analysis showed higher NT-proBNP (HR＝1.1,5%CI:1.00～1.01) and LAVI (HR＝1.6,5%CI:1.04～1.30), as well as lower SDNN (HR＝0.4,5%CI:0.91～0.98), were independently associated with an increased risk of MACE, whereas dapagliflozin use was an independent protective factor (HR＝0.8,5%CI:0.07～0.45) (all P＜0.05). The patients were divided into low-HRV and high-HRV groups according to the median SDNN (82 ms). Kaplan-Meier survival analysis showed that the difference in MACE-free survival rates between the two groups was statistically significant (P＝0.0043). Conclusion Reduced HRV, especially SDNN, was significantly associated with an increased risk of MACE in elderly female patients with HFpEF and T2DM, suggesting that HRV may serve as a valuable indicator for evaluating autonomic dysfunction and adverse cardiovascular prognosis in this population.
