Point-of-care ß-hydroxybutyrate measurement predicts adequate glucose metabolism suppression in cardiac FDG-PET/CT.

AIMS: The aims of our study were to evaluate whether point-of-care ß-hydroxybutyrate (BHB) measurement can be used to identify patients with adequate cardiac glucose metabolism suppression for cardiac [18F]-fluoro-2-deoxy- d-glucose-positron emission tomography with computerized tomography (FDG-PET/CT) and to develop a pretest probability calculator of myocardial suppression using other metabolic factors attainable before imaging. METHODS AND RESULTS: We recruited 193 patients with any clinical indication for whole body [18F]-FDG-PET/CT. BHB level was measured with a point-of-care device. Maximal myocardial standardized uptake value using lean body mass (SULmax) was measured from eight circular regions of interest with 1 cm circumference and background from left ventricular blood pool. Correlations SULmax and point-of-care measured BHB were analysed. The ability of BHB test to predict adequate suppression was evaluated with receiver operating characteristic analysis. Liver and spleen attenuation in computed tomography were measured to assess the presence of fatty liver. BHB level correlated with myocardial uptake and, using a cut-off value of 0.35 mmol/L to predict adequate myocardial suppression, we reached specificity of 90% and sensitivity of 56%. Other variables to predict adequate suppression were diabetes, obesity, ketogenic diet and fatty liver. Using information attainable before imaging, we created a pretest probability calculator of inadequate myocardial glucose metabolism suppression. The area under the curve for BHB test alone was 0.802 and was 0.857 for the pretest calculator (p = 0.319). CONCLUSIONS: BHB level measured with a point-of-care device is useful in predicting adequate myocardial glucose metabolism suppression. More detailed assessment of other factors potentially contributing to cardiac metabolism is needed.

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.

Vanadia-Zirconia and Vanadia-Hafnia Catalysts for Utilization of Volatile Organic Compound Emissions.

Utilization is a sustainable and interesting alternative for the destructive treatment of volatile organic compounds due to avoided CO2 emission. This work concentrates on the development of active and sulfur-tolerant catalysts for the utilization of contaminated methanol. Impregnated and sol-gel prepared vanadia-zirconia and vanadia-hafnia catalysts were thoroughly characterized by N2 sorption, analytical (S)TEM, elemental analysis, XRD and Raman spectroscopy, and their performances were evaluated in formaldehyde production from methanol and methanethiol mixture. The results showed higher activity of the sol-gel prepared catalysts due to formation of mono- and polymeric vanadia species. Unfortunately, the most active vanadia sites were deactivated more easily than the metal-mixed oxide HfV2O7 and ZrV2O7 phases, as well as crystalline V2O5 observed in the impregnated catalysts. Metal-mixed oxide phases were formed in impregnated catalysts through formation of defects in HfO2 and ZrO2 structure during calcination at 600 °C, which was evidenced by Raman spectroscopy. The sol-gel prepared vanadia-zirconia and vanadia-hafnia catalysts were able to produce formaldehyde from contaminated methanol with high selectivity at temperature around 400 °C, while impregnated catalysts required 50-100 °C higher temperatures.

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.

Carotid Wall Longitudinal Motion in Ultrasound Imaging: An Expert Consensus Review.

Motion extracted from the carotid artery wall provides unique information for vascular health evaluation. Carotid artery longitudinal wall motion corresponds to the multiphasic arterial wall excursion in the direction parallel to blood flow during the cardiac cycle. While this motion phenomenon has been well characterized, there is a general lack of awareness regarding its implications for vascular health assessment or even basic vascular physiology. In the last decade, novel estimation strategies and clinical investigations have greatly advanced our understanding of the bi-axial behavior of the carotid artery, necessitating an up-to-date review to summarize and classify the published literature in collaboration with technical and clinical experts in the field. Within this review, the state-of-the-art methodologies for carotid wall motion estimation are described, and the observed relationships between longitudinal motion-derived indices and vascular health are reported. The vast number of studies describing the longitudinal motion pattern in plaque-free arteries, with its putative application to cardiovascular disease prediction, point to the need for characterizing the added value and applicability of longitudinal motion beyond established biomarkers. To this aim, the main purpose of this review was to provide a strong base of theoretical knowledge, together with a curated set of practical guidelines and recommendations for longitudinal motion estimation in patients, to foster future discoveries in the field, toward the integration of longitudinal motion in basic science as well as clinical practice.

Electrical and mechanical dyssynchrony in patients with right bundle branch block.

BACKGROUND: Though fairly benign reputation, the right bundle branch block (RBBB) can cause left ventricular mechanical dyssynchrony (LVMD). Still, the relationship between electrical disturbance and LVMD is partly unclear among these patients. METHODS: Thirty patients with RBBB and 60 matching controls were studied with vector electrocardiography and myocardial perfusion imaging phase analysis. RBBB group was divided into those with and those without LVMD. RESULTS: Prevalence of LVMD among RBBB patients was 50% and among controls 22%. Odds ratio (OR) for LVMD in patients with RBBB vs controls without RBBB was 3.6 (95% CI 1.4 to 9.3). Ejection fraction (EF), end-systolic volume, the angle between QRS and T vectors, and the QRS angle in the sagittal plane were significantly different between RBBB patients with and without LVMD. The QRS duration was comparable in these groups. EF associated independently with LVMD, explaining 60% of its variation. A cut-off value of EF ≤ 55% detected LVMD in 100% specificity (sensitivity of 47%). CONCLUSION: Half of the patients with RBBB had LVMD. The OR for LVMD between RBBB and normal ECG was 3.6. It seems that EF, rather than electrical parameters, is the main determinant of LVMD. This information might be useful when evaluating indications for cardiac resynchronization therapy.

Relationships between electrical and mechanical dyssynchrony in patients with left bundle branch block and healthy controls.

BACKGROUND: Abnormal electrical activation may cause dyssynchronous left ventricular (LV) contraction. In this study, we characterized and analyzed electrical and mechanical dyssynchrony in patient with left bundle branch block (LBBB) and healthy controls. METHODS: Myocardial perfusion imaging (MPI) data from 994 patients were analyzed. Forty-three patient fulfilled criteria for LBBB and 24 for controls. Electrical activation was characterized with vector electrocardiography (VECG) and LV function including mechanical dyssynchrony with ECG-gated MPI phase analysis. RESULTS: QRS duration (QRSd; r = 0.69, P < .001) and a few other VECG parameters correlated significantly with phase bandwidth (phaseBW) representing mechanical dyssynchrony. End-diastolic volume (EDV; r = 0.59, P < .001), ejection fraction and end-systolic volume correlated also with phaseBW. QRSd (ß = 0.47, P < .001) and EDV (ß = 0.36, P = .001) were independently associated with phaseBW explaining 55% of its variation. Sixty percent of patients with LBBB had significant mechanical dyssynchrony. Those patients had wider QRSd (159 vs 147 ms, P = .013) and larger EDV (144 vs 94 mL, P = .008) than those with synchronous LV contraction. Cut-off values for mechanical dyssynchrony seen in patients with LBBB were QRSd ≥ 165 ms and EDV ≥ 109 mL. CONCLUSIONS: Despite obvious conduction abnormality, LBBB is not always accompanied by mechanical dyssynchrony. QRSd and EDV explained 55% of variation seen in phaseBW. These two parameters were statistically different between LBBB cases with and without mechanical dyssynchrony.

Fibrosis and wall thickness affect ventricular repolarization dynamics in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by ventricular repolarization abnormalities and risk of ventricular arrhythmias. Our aim was to study the association between the phenotype and ventricular repolarization dynamics in HCM patients. METHODS: HCM patients with either the MYBPC3-Q1061X or TPM1-D175N mutation (n = 46) and control subjects without mutation and hypertrophy (n = 35) were studied with 24-hr ambulatory ECG recordings by measuring time intervals of rate-adapted QT (QTe), maximal QT, and T-wave apex to wave end (TPE) intervals and the QTe/RR slope. Findings were correlated to specified echocardiographic and cardiac magnetic resonance imaging (CMRI) findings. RESULTS: Rate-adapted QTe interval was progressively longer in HCM patients with decreasing heart rates compared to control subjects (p = 0.020). The degree of hypertrophy correlated with measured QTe values. HCM patients with maximal wall thickness higher than the mean (20.6 mm) had longer maximum QTe and median TPE intervals compared to control subjects and HCM patients with milder hypertrophy (p < 0.001 and p = 0.014, respectively). HCM patients with late gadolinium enhancement (LGE) on CMRI had steeper QTe/RR slopes compared to HCM patients without LGE and control subjects (p = 0.044 and p = 0.001, respectively). LGE was an independent predictor of QTe/RR slope (p = 0.023, B = 0.043). CONCLUSION: Dynamics of ventricular repolarization in HCM are affected by hypertrophy and fibrosis. LGE may confer an independent effect on QT dynamics which may increase the arrhythmogenic potential in HCM.

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.

Reference values for left ventricular systolic synchrony according to phase analysis of ECG-gated myocardial perfusion SPECT.

BACKGROUND: The aim of this study was to define reference values for left ventricular systolic synchrony and for the volume parameters of the left ventricle using myocardial perfusion SPECT-derived phase analysis method. METHODS: We evaluated data of 433 patients who underwent myocardial perfusion SPECT/CT during January 2012-February 2013 in Kuopio University Hospital. The final study population consisted of 52 patients (aged 42-84 years) who met the criteria: (1) no previously diagnosed cardiac disease, (2) normal ECG at rest, (3) no advanced coronary artery disease in CT and 4) normal myocardial perfusion in stress/rest myocardial perfusion SPECT/CT. The severity of mechanical dyssynchrony was assessed by phase analysis of gated myocardial SPECT at stress stage after pharmacological exercise and at rest using Quantitative Gated SPECT (QGS) software. Volume parameters of the left ventricle were also assessed. RESULTS: The phase histogram bandwidth at rest was 28.0 [63.7] degrees (median [95th percentile]). The standard deviation of phase histogram at rest was 7.8 [26.5] degrees. Entropy at the rest study was 54.0 [63.7] %. All left ventricular dyssynchrony parameters were statistically significantly higher at stress compared to rest. There were no statistically significant differences in dyssynchrony values between men and women. In volume parameters, reference values in male were expectedly higher than in female. Cardiac output did not differ significantly between genders. CONCLUSION: In subjects without signs of cardiac diseases, the left ventricular systolic function is well synchronized. Phase analysis measurement does not depend on gender, age, BMI or blood pressure, but the values of dyssynchrony parameters increase during pharmacological stress.

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).