Assessment of cardiovascular regulation through irreversibility analysis of heart period variability: a 24 hours Holter study in healthy and chronic heart failure populations

We propose an approach based on time reversibility analysis to characterize the cardiovascular regulation and its nonlinearities as derived from 24 hours Holter recordings of heart period variability in a healthy population (n=12, age: median=43 years, range=34–55 years) and in a pathological group of age-matched chronic heart failure (CHF) patients (n=13, primarily in NYHA class II, age: median=37 years, range=33–56 years, ejection fraction: median=25%, range=13–30%). Two indices capable of detecting nonlinear irreversible dynamics according to different strategies of phase-space reconstruction (i.e. a fixed two-dimensional phase-space reconstruction and an optimal selection of the embedding dimension, respectively) are tested and compared with a more traditional nonlinear index based on local nonlinear prediction. Results showed that nonlinear dynamics owing to time irreversibility at short time scales are significantly present during daytime in healthy subjects, more frequently present in the CHF population and less frequently during night-time in both groups, thus suggesting their link with a dominant sympathetic regulation and/or with a vagal withdrawal. On the contrary, nonlinear dynamics owing to time irreversibility at longer, dominant time scales were insignificantly present in both groups. During daytime in the healthy population, irreversibility was mostly due to the presence of asymmetric patterns characterized by bradycardic runs shorter than tachycardic ones. Nonlinear dynamics produced by mechanisms different from those inducing temporal irreversibility were significantly detectable in both groups and more frequently during night-time. The present study proposes a method to distinguish different types of nonlinearities and assess their contribution over different temporal scales. Results confirm the usefulness of this method even when applied in uncontrolled experimental conditions such as those during 24 hours Holter recordings

Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study

In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised

Relationship between fractal dimension and power-law exponent of heart rate variability in normal and heart failure subjects

Among the plethora of indices that can describe the fractal-like behaviour of heart rate variability (HRV), the fractal dimension (FD) and the power-law exponent (β) have gained wide acceptance. Since HRV is generally modelled with fractional Brownian motion (fBm), the linear scaling relationship between β and FD, valid for fBm, is often applied to HRV series to derive one index from the other. In this paper the relationship between β and FD is calculated in normal (NR) and heart failure (HF) HRV series. Results revealed that a linear dependence between β and FD can be found only when the slope of the spectral density is calculated over the whole spectrum instead of considering more widespread very low frequency ranges. Moreover, the relationship is slightly different from that characterizing fBm and is not unique for the two categories of subjects. The common practice of estimating β from FD for HRV applying the theoretical relationship should be reconsidered

FHRV assessment by means of symbolic dynamics

The foetal heart rate variability is one of the most important parameters to monitor the health of the foetus. There are so many studies, both in time and frequency domain, which analyze the foetal heart rate variability and showed its significant diagnostic value. However, these studies have shown some limitations in highlighting some of the dynamics potentially relevant in controlling of heart rate. Therefore, methods of non-linear analysis have obtained a growing interest to analyze the chaotic nature of heart activity and they have already been successfully used in adults. As for foetal monitoring, much less works are available. Recently, symbolic dynamics has been used to quantify the regularity of foetal heart rate, showing that its use can lead to a more complete and thorough understanding of normal physiological development of the foetus. In this work, we applied symbolic dynamics to analyze foetal heart rate variability in healthy foetuses at the end of a normal pregnancy. The results confirmed the potential of this method in emphasizing the differences between signals characterized by greater or lesser variability

Circadian variations of short-term heart period irreversibility in healthy and chronic heart failure patients

We exploited time irreversibility analysis to characterize short heart period sequences (256 samples) derived from 24h Holter recordings in normal healthy (NO) subjects and chronic heart failure (CHF) patients. We found a significant presence of irreversible dynamics over short time scales, whereas over dominant, longer time scales irreversibility was marginal. Over short time scales in NO subjects the percentage of irreversible dynamics was larger during daytime than during nighttime, thus indicating a larger presence of non linear dynamics during daytime. Same circadian variation was detected in CHF patients but the percentage of irreversible series was higher. In NO subjects during daytime the non linear behavior was mostly the result of bradycardic runs shorter than tachycardic ones. In CHF population this pattern was as present as the reverse pattern (i.e. tachycardic runs shorter than bradycardic ones). Time irreversibility analysis provides useful and reliable indexes even in uncontrolled experimental conditions and during daily activities

A new tool for foetal phonocardiography simulation

Among diagnostic techniques for foetal monitoring, phonocardiography is gaining more and more interest for its low cost, passive nature and capability to detect some cardiac diseases. In spite of these characteristics, its use in clinical routine is still limited due to different troubles; for example, signals recorded through maternal abdomen show generally a quite low signal-to-noise ratio, so that detection and analysis of foetal heart sounds result very difficult. In this scenario, the availability of artificial phonocardiographic signals, simulated with conditions resembling different foetal conditions, week of gestation and noise amount, to name someone, can be a very useful tool to train medical staff. In this paper a software for phonocardiography simulation, updated to take account also of the split is presented. The software is completed with a user interface which allow to modify in a simple way simulation parameters. It is worth highlighting that this software can be useful also for testing performances of other analysis software and mathematical tools for recognising of valves components in the heart sounds