Short-term Heart Rate Turbulence Analysis Versus Variability and Baroreceptor Sensitivity in Patients With Dilated Cardiomyopathy

New methods for the analysis of arrhythmias and their hemodynamic consequences have been applied in risk stratification, in particular to patients after myocardial infarction. This study investigates the suitability of short-term heart rate turbulence (HRT) analysis in comparison to heart rate and blood pressure variability as well as baroreceptor sensitivity analyses to characterise the regulatory differences between patients with dilated cardiomyopathy (DCM) and healthy controls. In this study, 30 minutes data of non-invasive continuous blood pressure and ECGs of 37 DCM patients and 167 controls measured under standard resting conditions were analysed. The results show highly significant differences between DCM patients and controls in heart rate and blood pressure variability as well as in baroreceptor sensitivity parameters. Applying a combined heart rate-blood pressure trigger, ventricular premature beats were detected in 24.3% (9) of the DCM patients and 11.3% (19) of the controls. This fact demonstrates the limited applicability of short-term HRT analyses. However, the HRT parameters showed significant differences in this subgroup with ventricular premature beats (turbulence onset: DCM: 1.80±2.72, controls: - 4.34±3.10, p<0.001; turbulence slope: DCM: 6.75±5.50, controls: 21.30±17.72, p=0.021). Considering all (including HRT) parameters in the subgroup with ventricular beats, a discrimination rate between DCM patients and controls of 88.0% was obtained (max. 6 parameters). The corresponding value obtained for the total group was 86.3% (without HRT parameters). Comparable classification rates and high correlations between heart rate turbulence and variability and baroreflex parameters point to a more universal applicability of the latter methods

Sleep apnea-hypopnea quantification by cardiovascular data analysis

Sleep apnea is the most common sleep disturbance and it is an important risk factor for cardiovascular disorders. Its detection relies on a polysomnography, a combination of diverse exams. In order to detect changes due to sleep disturbances such as sleep apnea occurrences, without the need of combined recordings, we mainly analyze systolic blood pressure signals (maximal blood pressure value of each beat to beat interval). Nonstationarities in the data are uncovered by a segmentation procedure, which provides local quantities that are correlated to apnea-hypopnea events. Those quantities are the average length and average variance of stationary patches. By comparing them to an apnea score previously obtained by polysomnographic exams, we propose an apnea quantifier based on blood pressure signal. This furnishes an alternative procedure for the detection of apnea based on a single time series, with an accuracy of 82%

Pathological Heart Rate Regulation in Apparently Healthy Individuals

Cardiovascular diseases are the leading cause of morbidity and mortality in adults worldwide. There is one common pathophysiological aspect present in all cardiovascular diseases—dysfunctional heart rhythm regulation. Taking this aspect into consideration for cardiovascular risk predictions opens important research perspectives, allowing for the development of preventive treatment techniques. The aim of this study was to find out whether certain pathologically appearing signs in the heart rate variability (HRV) of an apparently healthy person, even with high HRV, can be defined as biomarkers for a disturbed cardiac regulation and whether this can be treated preventively by a drug-free method. This multi-phase study included 218 healthy subjects of either sex, who consecutively visited the physician at Gesundheit clinic because of arterial hypertension, depression, headache, psycho-emotional stress, extreme weakness, disturbed night sleep, heart palpitations, or chest pain. In study phase A, baseline measurement to identify individuals with cardiovascular risks was done. Therefore, standard HRV, as well as the new cardiorhythmogram (CRG) method, were applied to all subjects. The new CRG analysis used here is based on the recently introduced LF drops and HF counter-regulation. Regarding the mechanisms of why these appear in a steady-state cardiorhythmmogram, they represent non-linear event-based dynamical HRV biomarkers. The next phase of the study, phase B, tested whether the pathologically appearing signs identified via CRG in phase A could be clinically influenced by drug-free treatment. In order to validate the new CRG method, it was supported by non-linear HRV analysis in both phase A and in phase B. Out of 218 subjects, the pathologically appearing signs could be detected in 130 cases (60%), p < 0.01, by the new CRG method, and by the standard HRV analysis in 40 cases (18%), p < 0.05. Thus, the CRG method was able to detect 42% more cases with pathologically appearing cardiac regulation. In addition, the comparative CRG analysis before and after treatment showed that the pathologically appearing signs could be clinically influenced without the use of medication. After treatment, the risk group decreased eight-fold—from 130 people to 16 (p < 0.01). Therefore, progression of the detected pathological signs to structural cardiac pathology or arrhythmia could be prevented in most of the cases. However, in the remaining risk group of 16 apparently healthy subjects, 8 people died due to all-cause mortality. In contrast, no other subject in this study has died so far. The non-linear parameter which is able to quantify the changes in CRGs before versus after treatment is FWRENYI4 (symbolic dynamic feature); it decreased from 2.85 to 2.53 (p < 0.001). In summary, signs of pathological cardiac regulation can be identified by the CRG analysis of apparently healthy subjects in the early stages of development of cardiac pathology. Thus, our method offers a sensitive biomarker for cardiovascular risks. The latter can be influenced by non-drug treatments (acupuncture) to stop the progression into structural cardiac pathologies or arrhythmias in most but not all of the patients. Therefore, this could be a real and easy-to-use supplemental method, contributing to primary prevention in cardiology.Peer Reviewe

Cardio-Respiratory Coordination Increases during Sleep Apnea

Funding: MR, NW, AM, TP and JK acknowledge financial support from RI2916/2-1, WE2834/5-1, PE628/4-1, and KU837/23-1 (Deutsche Forschungsgemeinschaft). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Quantifying Effects of Pharmacological Blockers of Cardiac Autonomous Control Using Variability Parameters

Objective: The aim of this study was to identify the most sensitive heart rate and blood pressure variability (HRV and BPV) parameters from a given set of well-known methods for the quantification of cardiovascular autonomic function after several autonomic blockades. Methods: Cardiovascular sympathetic and parasympathetic functions were studied in freely moving rats following peripheral muscarinic (methylatropine), β1-adrenergic (metoprolol), muscarinic + β1-adrenergic, α1-adrenergic (prazosin), and ganglionic (hexamethonium) blockades. Time domain, frequency domain and symbolic dynamics measures for each of HRV and BPV were classified through paired Wilcoxon test for all autonomic drugs separately. In order to select those variables that have a high relevance to, and stable influence on our target measurements (HRV, BPV) we used Fisher's Method to combine the p-value of multiple tests. Results: This analysis led to the following best set of cardiovascular variability parameters: The mean normal beat-to-beat-interval/value (HRV/BPV: meanNN), the coefficient of variation (cvNN = standard deviation over meanNN) and the root mean square differences of successive (RMSSD) of the time domain analysis. In frequency domain analysis the very-low-frequency (VLF) component was selected. From symbolic dynamics Shannon entropy of the word distribution (FWSHANNON) as well as POLVAR3, the non-linear parameter to detect intermittently decreased variability, showed the best ability to discriminate between the different autonomic blockades. Conclusion: Throughout a complex comparative analysis of HRV and BPV measures altered by a set of autonomic drugs, we identified the most sensitive set of informative cardiovascular variability indexes able to pick up the modifications imposed by the autonomic challenges. These indexes may help to increase our understanding of cardiovascular sympathetic and parasympathetic functions in translational studies of experimental diseases.Peer Reviewe

Piscine orthoreovirus infection in Atlantic salmon (Salmo salar) protects against subsequent challenge with infectious hematopoietic necrosis virus (IHNV)

Abstract Infectious hematopoietic necrosis virus (IHNV) is endemic in farmed rainbow trout in continental Europe and in various salmonid fish species at the Pacific coast of North America. IHN has never occurred in European Atlantic salmon (Salmo salar) farms, but is considered as a major threat for the European salmon industry. Another virus, Piscine orthoreovirus (PRV), is widespread in the sea phase of Atlantic salmon, and is identified as the causative agent of heart and skeletal muscle inflammation. The aim of this study was to investigate the interactions between a primary PRV infection and a secondary IHNV infection under experimental conditions. A PRV cohabitation challenge was performed with Atlantic salmon. At peak of PRV viremia the fish were challenged by immersion with an IHNV genogroup E isolate. Clinical signs and morbidity were monitored. Target organs were sampled at selected time points to assess viral loads of both pathogens. Antiviral immune response and presence of histopathological findings were also investigated. Whereas the PRV-negative/IHNV positive group suffered significant decrease in survival caused by IHNV, the PRV infected groups did not suffer any morbidity and showed negligible levels of IHNV infection. Antiviral response genes were induced, as measured in spleen samples, from PRV infected fish prior to IHNV challenge. In conclusion, PRV-infection protects Atlantic salmon against IHNV infection and morbidity, most likely by inducing a protective innate antiviral response