Cardiac remodelling in association with left ventricular dyssynchrony and systolic dysfunction in patients with coronary artery disease.

BACKGROUND: In patients with coronary artery disease (CAD), ischaemic cardiomyopathy may result in progressive cardiac remodelling and left ventricular (LV) dysfunction. Myocardial perfusion imaging (MPI) can be used to quantify LV size and shape, mechanical dyssynchrony (LVMD) and ejection fraction (EF) as well as myocardial ischaemia and injury extents. We investigated the prevalence of LV remodelling (LVR) in patients with CAD and the relationship between LVR, LVMD and EF. METHODS: Three hundred twenty-six patients with CAD were evaluated. The EF and end-diastolic volume (EDV) were measured using MPI. LVMD was assessed using phase analysis. LVR was characterised according to LV dilatation or increased shape indices (systolic shape index [SIES] and diastolic shape index [SIED]). RESULTS: LVR were observed in 41% of CAD patients. EDV, SIES and SIED were larger in patients with LVMD or low EF. After adjustment for age, sex and infarct and ischaemia extents, phase histogram bandwidth correlated with EDV (r = 0.218) and SIES (r = 0.266) and EF correlated with EDV (r = -0.535), SIES (r = -0.554) and SIED (r = -0.217, p < 0.001 for all). CONCLUSIONS: LVR is frequently seen in patients with CAD and may be detected even before the development of symptomatic heart failure. A large LV volume and a more spherical-shaped LV were associated with LVMD and low EF, highlighting the close relationships between remodelling and systolic dyssynchrony and dysfunction. MPI is useful for assessing LVR by providing information about LV size and shape, which changes from an ellipsoid towards a spherical form in the development of ischaemic cardiomyopathy.

Continuous mHealth Patch Monitoring for the Algorithm-Based Detection of Atrial Fibrillation: Feasibility and Diagnostic Accuracy Study.

BACKGROUND: The detection of atrial fibrillation (AF) is a major clinical challenge as AF is often paroxysmal and asymptomatic. Novel mobile health (mHealth) technologies could provide a cost-effective and reliable solution for AF screening. However, many of these techniques have not been clinically validated. OBJECTIVE: The purpose of this study is to evaluate the feasibility and reliability of artificial intelligence (AI) arrhythmia analysis for AF detection with an mHealth patch device designed for personal well-being. METHODS: Patients (N=178) with an AF (n=79, 44%) or sinus rhythm (n=99, 56%) were recruited from the emergency care department. A single-lead, 24-hour, electrocardiogram-based heart rate variability (HRV) measurement was recorded with the mHealth patch device and analyzed with a novel AI arrhythmia analysis software. Simultaneously registered 3-lead electrocardiograms (Holter) served as the gold standard for the final rhythm diagnostics. RESULTS: Of the HRV data produced by the single-lead mHealth patch, 81.5% (3099/3802 hours) were interpretable, and the subject-based median for interpretable HRV data was 99% (25th percentile=77% and 75th percentile=100%). The AI arrhythmia detection algorithm detected AF correctly in all patients in the AF group and suggested the presence of AF in 5 patients in the control group, resulting in a subject-based AF detection accuracy of 97.2%, a sensitivity of 100%, and a specificity of 94.9%. The time-based AF detection accuracy, sensitivity, and specificity of the AI arrhythmia detection algorithm were 98.7%, 99.6%, and 98.0%, respectively. CONCLUSIONS: The 24-hour HRV monitoring by the mHealth patch device enabled accurate automatic AF detection. Thus, the wearable mHealth patch device with AI arrhythmia analysis is a novel method for AF screening. TRIAL REGISTRATION: ClinicalTrials.gov NCT03507335; https://clinicaltrials.gov/ct2/show/NCT03507335.

Automatic Mobile Health Arrhythmia Monitoring for the Detection of Atrial Fibrillation: Prospective Feasibility, Accuracy, and User Experience Study.

BACKGROUND: Atrial fibrillation (AF) is the most common tachyarrhythmia and associated with a risk of stroke. The detection and diagnosis of AF represent a major clinical challenge due to AF's asymptomatic and intermittent nature. Novel consumer-grade mobile health (mHealth) products with automatic arrhythmia detection could be an option for long-term electrocardiogram (ECG)-based rhythm monitoring and AF detection. OBJECTIVE: We evaluated the feasibility and accuracy of a wearable automated mHealth arrhythmia monitoring system, including a consumer-grade, single-lead heart rate belt ECG device (heart belt), a mobile phone application, and a cloud service with an artificial intelligence (AI) arrhythmia detection algorithm for AF detection. The specific aim of this proof-of-concept study was to test the feasibility of the entire sequence of operations from ECG recording to AI arrhythmia analysis and ultimately to final AF detection. METHODS: Patients (n=159) with an AF (n=73) or sinus rhythm (n=86) were recruited from the emergency department. A single-lead heart belt ECG was recorded for 24 hours. Simultaneously registered 3-lead ECGs (Holter) served as the gold standard for the final rhythm diagnostics and as a reference device in a user experience survey with patients over 65 years of age (high-risk group). RESULTS: The heart belt provided a high-quality ECG recording for visual interpretation resulting in 100% accuracy, sensitivity, and specificity of AF detection. The accuracy of AF detection with the automatic AI arrhythmia detection from the heart belt ECG recording was also high (97.5%), and the sensitivity and specificity were 100% and 95.4%, respectively. The correlation between the automatic estimated AF burden and the true AF burden from Holter recording was >0.99 with a mean burden error of 0.05 (SD 0.26) hours. The heart belt demonstrated good user experience and did not significantly interfere with the patient's daily activities. The patients preferred the heart belt over Holter ECG for rhythm monitoring (85/110, 77% heart belt vs 77/109, 71% Holter, P=.049). CONCLUSIONS: A consumer-grade, single-lead ECG heart belt provided good-quality ECG for rhythm diagnosis. The mHealth arrhythmia monitoring system, consisting of heart-belt ECG, a mobile phone application, and an automated AF detection achieved AF detection with high accuracy, sensitivity, and specificity. In addition, the mHealth arrhythmia monitoring system showed good user experience. TRIAL REGISTRATION: ClinicalTrials.gov NCT03507335; https://clinicaltrials.gov/ct2/show/NCT03507335.

Test-Retest Reliability of the Assessment of Fatty Liver Disease Using Low-Dose Computed Tomography in Cardiac Patients.

Non-alcoholic fatty liver disease (NAFLD) is a common disorder that is associated with the risk of cardiovascular diseases. Therefore, its prevalence is high in patients with coronary artery disease. In myocardial perfusion imaging (MPI), low-dose computed tomography (CT) scans are used for attenuation correction in separate stress and rest studies. Here, the test-retest reliability of CT-based quantification of NAFLD was evaluated using these two CT scans. The study population consisted of 261 patients (156 men and 105 women, age 66 ± 10 years). Quantification of liver fat content was based on the radiodensity of the liver in Hounsfield units as well as in relation to corresponding values of the spleen. NAFLD was observed in 47 subjects (18%). CT quantification has good test-retest reliability in assessing NAFLD, with concordance correlation coefficient (CCC) ranging from 0.512 to 0.923, intraclass correlation coefficient (ICC) ranging from 0.513 to 0.923, and coefficient of variation ranging from 3.1 to 7.0%. Regarding the liver to spleen ratio, CCC for non-NAFLD patients and NAFLD patients was 0.552 and 0.911, respectively. For non-NAFLD patients ICC was 0.553 and NAFLD patients it was 0.913. The coefficient of variation for non-NAFLD and NAFLD patients was 4.9% and 3.1%, respectively. Our results suggest that low-dose CT is a feasible and well repeatable method but amount of liver fat contributes to repeatability. In NAFLD patients CCC and ICC were high reflecting excellent reliability, whereas in non-NAFLD patients test-retest reliability was moderate. Assessment of liver fat content can be used as additional information in studies where a CT scan has been done for other medical reasons, such as for low-dose attenuation correction CT along with MPI.

Carotid artery longitudinal wall motion alterations associated with metabolic syndrome and insulin resistance.

BACKGROUND AND AIMS: Our objective was to study relationships between the new biomarker of vascular health, carotid artery longitudinal wall motion (CALM) and metabolic syndrome (MetS). METHODS: Carotid ultrasound and assessment of MetS and its components were performed with 281 subjects aged 30-45 years. In the longitudinal motion analysis, the amplitude of motion and the antegrade-oriented and retrograde-oriented components of motion between the intima-media complex and adventitial layer of the common carotid artery wall were assessed. RESULTS: Metabolic syndrome, according to the harmonized criteria, was detected in 53 subjects (19%). MetS was significantly associated with increased antegrade and decreased retrograde longitudinal motion in the carotid artery wall. Augmented antegrade amplitude of longitudinal motion was associated with obesity (ß = 0.149, p < .05) and low HDL cholesterol (ß = 0.177, p < .01). Attenuated retrograde amplitude of longitudinal motion was associated with hypertension (ß = -0.156, p < .05), obesity (ß = -0.138, p < .05) and hyperinsulinaemia (ß = -0.158, p < .01). Moreover, insulin resistance (homeostasis model assessment index above 2.44) was associated with adverse changes in CALM. CONCLUSION: Metabolic syndrome and insulin resistance were associated with alterations in CALM. In particular, hypertension, obesity and hyperinsulinaemia were associated with reduced total peak-to-peak amplitude as well as increased antegrade and reduced retrograde amplitudes, all of which might be markers of unfavourable vascular health.

Severe Obstructive Sleep Apnea and Increased Cortical Amyloid-ß Deposition.

BACKGROUND: The suggested association between severe obstructive sleep apnea (OSA) and risk of Alzheimer's disease (AD) needs further study. Only few recent reports exist on associations between brain amyloid-ß (Aß) burden and severe OSA in middle-aged patients. OBJECTIVE: Examine the possible presence of cortical Aß accumulation in middle-aged patients with severe OSA. METHODS: We performed detailed multimodal neuroimaging in 19 cognitive intact patients (mean 44.2 years) with severe OSA (Apnea-Hypopnea Index >30 h-1). Known etiological factors for possible Aß accumulation were used as exclusion criteria. Aß uptake was studied with [11C]-PiB-PET, glucose metabolism with [18F]-FDG-PET, and structural imaging with 3.0T MRI. RESULTS: When analyzed individually, in [11C]-PiB-PET a substantial number (∼32%) of the patients exhibited statistically significant evidence of increased cortical Aß uptake based on elevated regional Z-score values, mostly seen bilaterally in the precuneus and posterior cingulum regions. Cortical glucose hypometabolism in [18F]-FDG-PET was seen in two patients. MRI did not show structural changes suggestive of AD-related pathology. CONCLUSION: Increased [11C]-PiB uptake was seen in middle-aged cognitively intact patients with severe OSA. These findings are similar to those described in cognitive unimpaired older OSA patients. The changes in cortical Aß uptake suggest that severe OSA itself may predispose to alterations related to AD already in middle-age. Aß clearance may be compromised without simultaneous evidence of metabolic or structural alterations. The results emphasize the importance of early diagnostics and proper treatment of severe OSA in cognitively intact middle-aged subjects, possibly diminishing the individual risk for later cognitive dysfunction.

Myocardial ischemia and previous infarction contribute to left ventricular dyssynchrony in patients with coronary artery disease.

AIMS: The aim of this study was to characterize determinants of left ventricular mechanical dyssynchrony (LVMD) in patients with coronary artery disease (CAD). METHODS: Medical records and results of myocardial perfusion SPECT/CT studies were evaluated in 326 patients with previously diagnosed CAD. LVMD was assessed with the phase analysis of ECG-gated myocardial SPECT. Dyssynchrony was described with phase histogram bandwidth (PHBW), standard deviation (PHSD) or entropy (PHE) values above limit of the highest normal. RESULTS: Prevalence of LVMD was 29% in CAD patients. Size of the infarction scar and ischemia extent correlated significantly with PHBW, PHSD and PHE (P < 0.001 for all). Independent predictors of LVMD were myocardial infarction scar (P = 0.004), ischemia extent (P = 0.003), and QRS duration (P = 0.003). Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony. CONCLUSIONS: Almost one-third of CAD patients had significant LVMD. Dyssynchrony was associated with earlier myocardial infarction and presence of myocardial ischemia. Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony.

Continuous 24-h Photoplethysmogram Monitoring Enables Detection of Atrial Fibrillation.

Aim: Atrial fibrillation (AF) detection is challenging because it is often asymptomatic and paroxysmal. We evaluated continuous photoplethysmogram (PPG) for signal quality and detection of AF. Methods: PPGs were recorded using a wrist-band device in 173 patients (76 AF, 97 sinus rhythm, SR) for 24 h. Simultaneously recorded 3-lead ambulatory ECG served as control. The recordings were split into 10-, 20-, 30-, and 60-min time-frames. The sensitivity, specificity, and F1-score of AF detection were evaluated for each time-frame. AF alarms were generated to simulate continuous AF monitoring. Sensitivities, specificities, and positive predictive values (PPVs) of the alarms were evaluated. User experiences of PPG and ECG recordings were assessed. The study was registered in the Clinical Trials database (NCT03507335). Results: The quality of PPG signal was better during night-time than in daytime (67.3 ± 22.4% vs. 30.5 ± 19.4%, p < 0.001). The 30-min time-frame yielded the highest F1-score (0.9536), identifying AF correctly in 72/76 AF patients (sensitivity 94.7%), only 3/97 SR patients receiving a false AF diagnosis (specificity 96.9%). The sensitivity and PPV of the simulated AF alarms were 78.2 and 97.2% at night, and 49.3 and 97.0% during the daytime. 82% of patients were willing to use the device at home. Conclusion: PPG wrist-band provided reliable AF identification both during daytime and night-time. The PPG data's quality was better at night. The positive user experience suggests that wearable PPG devices could be feasible for continuous rhythm monitoring.

Influence of cardiovascular risk factors on longitudinal motion of the common carotid artery wall.

BACKGROUND AND AIMS: Carotid artery longitudinal wall motion (CALM) is a new biomarker, which can be measured together with carotid intima-media thickness and distensibility measurements in the same session. Our objective was to study the relationship between these indicators of vascular health and cardiovascular risk factors in a large and well-characterized study population. METHODS: The study population consisted of 465 subjects aged 30-45 years. Successful measurements were performed in 287 participants. RESULTS: The peak-to-peak and retrograde amplitudes of the longitudinal motion were inversely correlated with systolic blood pressure (SBP; r = -0.152, p<0.05 and r = -0.189, p<0.01), diastolic blood pressure (DBP; r = -0.170, p<0.01 and r = -0.256, p<0.001) and body mass index (BMI; r = -0.158, p<0.01 and r = -0.291, p<0.001). In addition, retrograde amplitude of longitudinal motion indirectly correlated with total cholesterol and triglycerides (r = -0.163, p<0.01 and r = -0.228, p<0.001, respectively). Amplitude of antegrade longitudinal motion was directly correlated with DBP, total cholesterol, LDL-cholesterol, triglycerides and BMI (r = 0.198-0.274, p<0.001 for all). Antegrade longitudinal motion increased and retrograde longitudinal motion decreased with the increasing number of cardiovascular risk factors. CONCLUSIONS: The magnitude of correlation coefficients between CALM parameters and risk factors was comparable with those for carotid intima-media thickness and distensibility. However, the correlation profile for various risk factors was different and CALM gives additional information regarding arteriosclerosis and risk factors.

Cardiac repolarization during fingolimod treatment in patients with relapsing-remitting multiple sclerosis.

Background: Fingolimod is a sphingosine-1-phosphate receptor modulator for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite an established effect on heart rate, the effect of fingolimod on cardiac repolarization is not completely known. Methods: Twenty-seven patients with RRMS underwent 24-hr ambulatory ECG before fingolimod (baseline), at the day of fingolimod initiation (1D) and after three-month treatment (3M). The mean values of RR-interval as well as QT-interval corrected by Bazzet's (QTcBaz) and Fridericia's (QTcFri) formula were compared between baseline, 1D, and 3M over 24-hr period as well as at daytime and nighttime. Results: QTcBaz over 24-hr was shorter at 1D (414 ± 20 ms, p < .001) and at 3M (414 ± 20 ms, p < .001) than at baseline (418 ± 20 ms). In contrast, QTcFri over 24-hr was longer at 1D (410 ± 19 ms, p < .001) but similar at 3M (406 ± 19 ms, p = .355) compared to baseline (407 ± 19 ms). Daytime QTcBaz was shorter at 1D (p < .001) and at 3M (p = .007), whereas daytime QTcFri was longer at 1D (p < .05) but similar at 3M (p = ns) compared to baseline. During the night, changes were observed neither in QTcBaz nor in QTcFri between baseline, 1D, and 3M. Conclusions: Changes in cardiac repolarization after fingolimod initiation were mild and occurred at daytime. Ambiguously, QTcBaz demonstrated shortening, whereas QTcFri showed prolongation in cardiac repolarization after fingolimod initiation. The formula applied for QT-interval correction needs to be taken carefully into account as evaluating pharmacovigilance issues related to fingolimod.

Sequence of cardiovascular autonomic alterations after fingolimod initiation.

BACKGROUND: Homeostasis between heart rate and blood pressure is based on several interacting regulatory reflexes, which become influenced by fingolimod initiation. The aim of this study was to determine the sequence of changes in cardiovascular autonomic regulation after fingolimod initiation. METHODS: Twenty-seven patients with relapsing-remitting multiple sclerosis underwent continuous electrocardiogram recording during the first 6 hr after the first dose of fingolimod. In addition to the time interval between two consecutive R-peaks (RR interval), blood pressure and heart rate variability (HRV) were measured on hourly basis. Cardiac parasympathetic and sympathetic regulation were assessed by the different components of HRV. RESULTS: HRV demonstrated an enhancement in cardiac parasympathetic regulation starting 1 hr after the first dose of fingolimod. Blood pressure started to decrease 2 hr and sympathetic cardiac regulation 3 hr after fingolimod initiation. Recovery in RR interval, systolic and diastolic blood pressure, as well as in cardiac autonomic regulation started after 5 hr postdose, whereas pulse pressure (difference between systolic and diastolic blood pressure) continued to increase at the time of hospital discharge. CONCLUSIONS: RR interval, blood pressure, as well as the parasympathetic and sympathetic components of cardiac autonomic regulation alter sequentially in different temporal pattern after fingolimod initiation. These findings enhance the understanding of the effects of fingolimod initiation on cardiovascular autonomic regulation in real life.

Interrelationships between indices of longitudinal movement of the common carotid artery wall and the conventional measures of subclinical arteriosclerosis.

Our objective was to study the interrelationships between longitudinal movement of the wall of the common carotid artery and the conventional measures of arteriosclerosis in a large and well-characterized study population. Successful longitudinal movement analyses were performed on 292 subjects. The peak-to-peak and retrograde amplitudes of the longitudinal movement were directly correlated with carotid artery distensibility (r = 0·21, P<0·001 and r = 0·23, P<0·001, respectively) and inversely correlated with pulse wave velocity (r = -0·14, P<0·05 and r = -0·17, P<0·01, respectively). All longitudinal motion parameters were independent of brachial flow-mediated dilatation and intima-media thickness. Our findings indicate that arterial stiffening modulates longitudinal movement and, therefore, measurement of longitudinal movement can be of value in the assessment of vascular health.

Heart rate variability predicts the magnitude of heart rate decrease after fingolimod initiation.

BACKGROUND: Fingolimod is an immunomodulator with a disease modifying effect on relapsing-remitting multiple sclerosis (RRMS). A heart rate (HR) decrease shortly after fingolimod initiation, however, requires a clinical vigilance. The aim of this study was to prospectively investigate whether cardiac autonomic regulation can predict the magnitude of HR decrease after fingolimod initiation. METHODS: Twenty-five patients with RRMS underwent ambulatory 24-h electrocardiogram recording to assess HR variability 20±16 days before fingolimod initiation (baseline) and repeated at the day of fingolimod initiation to assess the magnitude of HR decrease. The percentage of normal RR-intervals with duration more than 50ms different from the previous normal RR-interval (pNN50) was calculated (among the other HR variability parameters) to assess cardiac autonomic regulation. The maximal HR decrease (ΔHR) after the first dose of fingolimod was assessed in absolute units (beats/min) and in percentage (%). RESULTS: The maximal ΔHR was -20±11 beats/min (-23±12%) on the average. pNN50 calculated at baseline correlated with ΔHR% (r=-0.657, p<0.001). A HR decrease ≥20% was found in 10/14 patients with pNN50≥10%. The positive and negative predictive values of pNN50≥10% to predict ΔHR≥20% were 83% and 69%, respectively leading to accuracy of 76%. CONCLUSIONS: Cardiac autonomic regulation (pNN50>10%) at baseline can be used to predict the magnitude of HR decrease after the first dose of fingolimod. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01704183).

Principal Component Analysis of the Longitudinal Carotid Wall Motion in Association with Vascular Stiffness: A Pilot Study.

The longitudinal motion of the carotid wall during a heart cycle has a multiphasic waveform. Recent studies have examined the amplitude of this motion. Instead of amplitude measurements, we focus on making a detailed characterization of the motion waveform. Two-minute carotid ultrasound videos were obtained for 19 healthy volunteers, and a speckle tracking algorithm was used to measure the motion of the carotid wall. Principal component analysis revealed the characteristic features of wall motion and their relation to known arterial stiffness indices. By estimating two principal components, we could account for more than 92% of the variation in the motion graphs. The first principal component derived from the longitudinal motion curves was significantly correlated to pulse pressure, indicating that the main dominant base waveform of the longitudinal motion was related to blood pressure. The second principal component derived from the longitudinal motion curves had multiple significant correlations to known stiffness indices, indicating that the stronger biphasic structure of the motion curve, especially on the adventitia layer, was associated with higher distensibility and compliance, as well as reduced carotid artery stiffness. According to this study, the second principal component of the longitudinal motion may be a useful parameter reflecting vascular health.

Modulation of sphingosine receptors influences circadian pattern of cardiac autonomic regulation.

Fingolimod is an oral sphingosine-1-phospate (S1P) receptor modulator for the treatment of relapsing-remitting multiple sclerosis (RRMS). In addition to therapeutic effects on lymphoid and neural tissue, fingolimod influences cardiovascular system by specific S1P-receptor modulation. The effects of S1P-receptor modulation on the endogenous circadian pattern of cardiac autonomic regulation (CAR), however, are not known. We examined the effects of fingolimod on the circadian pattern of CAR Ambulatory 24-h ECG recordings were undertaken in 27 RRMS patients before fingolimod (baseline), at the day of fingolimod initiation (1D) and after 3 months of fingolimod treatment (3M). The mean time between two consecutive R-peaks (RR-interval) and mean values for measures of heart rate variability (HRV) in time- and frequency domain were calculated from ECG recording at daytime and nighttime. The mean night:day-ratio of RR-interval was 1.23 ± 0.12 at baseline, decreased temporarily at 1D (1.16 ± 0.12; P < 0.01) and was higher at 3M (1.32 ± 0.11; P < 0.001) than at baseline. The night:day-ratio of HRV parameters reflecting parasympathetic cardiac regulation (pNN50, rMSSD, HFnu) decreased at 1D but recovered back to baseline at 3M (P < 0.05 for all). On the other hand, the night:day-ratio of TP, a parameter reflecting overall HRV gradually decreased and was lower at 3M than at baseline (P < 0.05). Our findings suggest that physiological relation between the circadian pattern of RR-interval and overall HRV as well as parasympathetic cardiac regulation becomes uncoupled during fingolimod treatment. In addition, fingolimod shifts the circadian equilibrium of CAR toward greater daytime dominance of overall HRV Accordingly, S1P-receptor modulation influences circadian pattern of CAR.

BMI influence on the reproducibility of ECG-gated myocardial perfusion imaging phase analysis in comparison with novel echocardiographic dyssynchrony estimation methods.

AIM: Cardiac resynchronization therapy (CRT) is a treatment for patients with end-stage heart failure. However, two-thirds of the patients are nonresponders. Evaluation of left ventricular mechanical dyssynchrony may help in finding patients who will benefit from CRT. Dyssynchrony can be evaluated by the phase analysis method in myocardial perfusion imaging (MPI) or with cardiac ultrasound. The aim of this study was to investigate the reproducibility of phase analysis parameters in MPI and echocardiographic parameters in the evaluation of left ventricular mechanical dyssynchrony. In particular, the influence of BMI on reproducibility was studied. METHODS AND RESULTS: Twenty-one patients underwent an ECG-gated MPI scan. Acquisition was repeated after the rest image. The patients were also studied twice with transthoracic echocardiography. Of MPI phase analysis parameters bandwidth, histogram SD and entropy% were highly reproducible in the pooled population: Cronbach's α 0.927-0.967 and intraclass correlation (ICC) 0.868-0.967, (P<0.001 for all). However, the reproducibility of bandwidth and SD was poorer in patients with BMI≥29 kg/m group (α 0.203 and -0.055; ICC 0.106 and -0.027, NS for both) than in those with BMI<29 kg/m (α 0.984 and 0.980; ICC 0.968 and 0.961, P<0.001 for both). In contrast, BMI had no obvious influence on the reproducibility of global longitudinal strain in echocardiography. CONCLUSION: Parameters reflecting mechanical dyssynchrony were found to be well reproducible. However, this study indicates that phase analysis results may be less reproducible in patients with high BMI, whereas global longitudinal strain in echocardiography seems to be less critical for a patient's BMI.

Transfer Function Analysis of the Longitudinal Motion of the Common Carotid Artery Wall.

The longitudinal motion of the carotid wall is a potential new measure of arterial stiffness. Despite the over decade long research on the subject, the driving force and the specific longitudinal kinetics of the carotid wall has remained unclear. In this study, a transfer function analysis with 20 healthy subjects is presented to derive how the energy from the blood pressure moves the innermost arterial wall longitudinally and how the kinetic energy is then transferred to the outermost arterial layer. The power spectrums display that the main kinetic energy of the longitudinal motion is on band 0-3 Hz with a peak on the 1.1 Hz frequency. There is a large variation among the individuals, how the energy from the blood pressure transfers into the longitudinal motion of the arterial wall since the main direction of the longitudinal motion varies individually and because early arterial stiffening potentially has an effect on the time characteristics of the energy transfer. The energy transfer from the innermost to the outermost wall layer is more straightforward: on average, a 17% of the longitudinal amplitude is lost and an 18.9 ms delay is visible on the 1.0 Hz frequency.

Effect of fingolimod on cardiac autonomic regulation in patients with multiple sclerosis.

BACKGROUND: Fingolimod modulates sphingosine-1-phosphate receptors that are also found in cardiovascular tissue. OBJECTIVE: To investigate the effects of fingolimod on cardiac autonomic regulation prospectively. METHODS: Twenty-seven relapsing-remitting multiple sclerosis patients underwent 24-hour electrocardiogram recording before, at the first day of fingolimod treatment (1d) and after three months of continuous dosing (3mo). The time interval between two consecutive R-peaks (RR-interval) was measured. Cardiac autonomic regulation was assessed by the various parameters of heart rate variability. Parasympathetic stimulation prolongs the RR-interval and increases heart rate variability while the effects of sympathetic stimulation are mainly the opposite. The low frequency/high frequency ratio reflects sympathovagal balance. RESULTS: From baseline to 1d, a prolongation of the RR-interval (P<0.001), an increase in the values of various heart rate variability parameters (P<0.05 to P<0.001) and a decrease in the low frequency/high frequency ratio (P<0.05) were demonstrated. At 3mo, although the RR-interval remained longer (P<0.01), the values of various heart rate variability parameters were lower (P<0.01 to P<0.001) as compared to baseline. At 3mo, the low frequency/high frequency ratio (P<0.05) was higher in men than in women although no such difference was found at baseline or at 1d. CONCLUSIONS: After an initial increase in parasympathetic regulation, continuous fingolimod dosing shifts cardiac autonomic regulation towards sympathetic predominance, especially in men. Careful follow-up of fingolimod-treated relapsing-remitting multiple sclerosis patients is warranted as sympathetic predominance associates generally with impaired outcome.ClinicalTrials.cov: NCT01704183.

New indices of arterial stiffness measured from longitudinal motion of common carotid artery in relation to reference methods, a pilot study.

BACKGROUND: Longitudinal wall motion of carotid artery is a useful but challenging parameter to measure. In this study, we tested our previously published motion tracking algorithm and validated our method against applanation tonometry measurements. METHODS AND RESULTS: We measured the two-dimensional carotid artery wall motion from 19 healthy subjects and, as a reference, performed applanation tonometry measurements in parallel with the ultrasound study. The results show that peak velocities (R = -0·484; P<0·05) and accelerations (R = -0·524; P<0·05) of the longitudinal motion between intima and adventitia layers exhibit a greater correlation with the arterial stiffness parameters, for example the augmentation index than the corresponding amplitude of the longitudinal motion (R = -0·132; P>0·05). The amplitudes of the longitudinal motion, between intima and adventitia, are related more to the physical size of the subject, as they correlated significantly with the height (R = 0·597; P<0·01) and weight (R = 0·562; P<0·05) of the subject as well as the cross-sectional dimension of the measured artery (R = 0·611; P<0·01). Furthermore, two new indices have been introduced, Polydeg and RAlength, with which to study the shape of the longitudinal motion curve; both parameters displayed significant correlation with arterial stiffness, for example augmentation index (R = 0·468; P<0·05 and R = 0·609; P<0·01, respectively). CONCLUSIONS: The new longitudinal motion parameters presented here displayed clear potential to be used as novel stiffness indices.

Mild obstructive sleep apnea does not modulate baroreflex sensitivity in adult patients.

BACKGROUND: Obstructive sleep apnea (OSA) is a chronic and progressive disease. OSA is associated with increased cardiovascular morbidity and mortality, the risk being more frequently encountered with severe degrees of OSA. Increased sympathetic activation and impaired cardiac autonomic control as reflected by depressed baroreceptor reflex sensitivity (BRS) are possible mechanisms involved in the cardiovascular complications of OSA. However, it is not known at what stage of OSA that changes in BRS appear. The aim of this study was to evaluate BRS in patients with mild OSA. METHODS: The study population consisted of 81 overweight patients with mild OSA and 46 body weight-matched non-OSA subjects. BRS, apnea-hypopnea index, body mass index, and metabolic parameters were assessed. The phenylephrine test was used to measure BRS. RESULTS: Patients in the OSA group were slightly but significantly older than the non-OSA population (50.3±9.3 years vs 45.7±11.1 years, P=0.02). Body mass index, percentage body fat, blood pressure, fasting glucose, insulin, and lipid levels did not differ between the OSA patients and non-OSA subjects. Absolute BRS values in patients with mild OSA and non-OSA subjects (9.97±6.70 ms/mmHg vs 10.51±7.16 ms/mmHg, P=0.67) and BRS values proportional to age-related and sex-related reference values (91.4%±22.7% vs 92.2%±21.8%, P=0.84) did not differ from each other. BRS <50% of the sex-specific reference value was found in 6% of patients with mild OSA and in 2% of non-OSA subjects (P=0.29). CONCLUSION: Patients with mild OSA did not show evidence of disturbed BRS in comparison with weight-matched non-OSA controls.