# Assessment of Cardiovascular Disease in Autosomal Dominant Polycystic Kidney Disease
## 5 Heart Rate Variability (HRV)  
In ADPKD patients, there is a dysregulation of the autonomic nervous system (ANS) [39]. The ANS is related to the cardiovascular system through heart rate control by the sympathetic and parasympathetic branches; catecholamines, released from the sympathetic nervous system, accelerate the heart rate. Additionally, contraction force and conduction are linked to sympathovagal balance, and changes in this equilibrium result in autonomic dysfunction. The assessment of heart rate variability (HRV) reflects the influence of ANS (sympathetic and parasympathetic) on the cardiovascular system. Since cardiovascular complications are the main causes of death in patients at different stage of CKD, it is important to assess HRV as sign of cardiovascular impairment. HRV is defined as the variation in time intervals between consecutive heart beats over a period of observation (time of recording). Commonly using an Electrocardiographic Holter-Recording, this period can last 24 h or 5-10 min (a long or short time of recording, respectively), representing both the time domain and frequency domain able to evaluate global autonomic activity with the standard deviation of all normal-to-normal intervals (SDNN), sympathetic activity with low frequency (LF), parasympathetic activity with high frequency (HF), and sympathovagal balance with a sympathetic/parasympathetic ratio (LF/HF ratio) (Figure 2). Sympathovagal influence on the sinoatrial node (SA node) is indicated by HRV, an indirect index of cardiac neural control. The increased activation of the sympathetic system, mainly expressed by LF, causes a variation in heart rate and can promote hypertension, myocardial hypertrophy, and fibrosis, conditions associated with the risk of sudden cardiac death [40]. HRV and QT corrected for heart rate (QTc) interval evaluation can help in evaluating the arrhythmic risk and the autonomic dysfunction of patients [41]. In advanced CKD, regardless of the cause, the alteration of the autonomic system expressed by changes in HRV parameters represents a predictive factor for the rapid progression of CKD. In an observational study by the National Taiwan University Hospital conducted in 326 nondialysis patients (median follow up period 2.02 years), a correlation between the late stage of CKD and low HRV was reported [42]. Among HRV parameters, SDNN, expressed as global autonomic function, LF (sympathetic system), HF (parasympathetic), and the LF/HF (sympathetic/parasympathetic) ratio were higher in early stages of CKD, while lower LF, HF, and LF/HF were correlated to late stages of CKD, which means a stronger compromission of ANS. Extremely lower LF and LF/HF were found in the rapid CKD progression group (diabetic and non-diabetic patients with worse values of serum creatinine, eGFR, proteinuria, albumin, hemoglobin, and HBA1c). Kidneys are directly innervated by the sympathetic nerve, which is one of the factors regulating the tubular and vascular function of glomeruli [42; 43; 44]. The pathogenic mechanism of autonomic dysfunction in ADPKD is not clear. Some hypotheses, such as uremic toxins, irregular erythropoietin secretion, and the overproduction of inflammatory mediators, are mentioned as causes of damage to autonomic kidney innervation. An imbalance between the sympathetic and parasympathetic system is also responsible for essential hypertension, which is the main feature of most ADPKD patients in the early stage of the disease. This is likely due to the presence and the enlargement of cysts in ADPKD, which cause an activation of the RAAS through renal arterial ischemia. A similar activation of RAAS is observed in bilateral atherosclerotic renal artery stenosis. RAAS activation causes autonomic dysfunction with sympathetic prevalence [41]. Increased sympathetic tone is also caused by the reduction in baroreflex sensitivity due to high arterial stiffness related to elevated blood pressure. This process can be found in hypertensive and ADPKD patients with hypertension, because it is related to both these diseases.