Publications by authors named "Pasi Karjalainen"

161 Publications

A Perturbed Postural Balance Test Using an Instrumented Treadmill - Precision and Accuracy of Belt Movement and Test-Retest Reliability of Balance Measures.

Front Sports Act Living 2021 27;3:688993. Epub 2021 Aug 27.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

A perturbed postural balance test can be used to investigate balance control under mechanical disturbances. The test is typically performed using purpose-built movable force plates. As instrumented treadmills become increasingly common in biomechanics laboratories and in clinical settings, these devices could be potentially used to assess and train balance control. The purpose of the study was to investigate how an instrumented treadmill applies to perturbed postural balance test. This was investigated by assessing the precision and reliability of the treadmill belt movement and the test-retest reliability of perturbed postural balance test over 5 days. Postural balance variables were calculated from the center of pressure trajectory and included peak displacement, time to peak displacement, and recovery displacement. Additionally, the study investigated short-term learning effects over the 5 days. Eight healthy participants (aged 24-43 years) were assessed for 5 consecutive days with four different perturbation protocols. Center of pressure (COP) data were collected using the force plates of the treadmill while participant and belt movements were measured with an optical motion capture system. The results show that the treadmill can reliably deliver the intended perturbations with <1% deviation in total displacement and with minimal variability between days and participants (typical errors 0.06-2.71%). However, the treadmill was not able to reach the programmed 4 m/s acceleration, reaching only about 75% of it. Test-retest reliability of the selected postural balance variables ranged from poor to good (ICC 0.156-0.752) with typical errors between 4.3 and 28.2%. Learning effects were detected based on linear or quadratic trends ( < 0.05) in peak displacement of the slow forward and fast backward protocols and in time to peak displacement in slow and fast backward protocols. The participants altered the initial location of the COP relative to the foot depending on the direction of the perturbation. In conclusion, the precision and accuracy of belt movement were found to be excellent. Test-retest reliability of the balance test utilizing an instrumented treadmill ranged from poor to good which is, in line with previous investigations using purpose-built devices for perturbed postural balance assessment.
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http://dx.doi.org/10.3389/fspor.2021.688993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429482PMC
August 2021

Wearable monitoring of positive and negative myoclonus in progressive myoclonic epilepsy type 1.

Clin Neurophysiol 2021 Jul 30;132(10):2464-2472. Epub 2021 Jul 30.

Kuopio Epilepsy Center, Neurocenter, Kuopio University Hospital, Full Member of ERN EpiCARE, Kuopio, Finland; Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.

Objective: To develop and test wearable monitoring of surface electromyography and motion for detection and quantification of positive and negative myoclonus in patients with progressive myoclonic epilepsy type 1 (EPM1).

Methods: Surface electromyography and three-dimensional acceleration were measured from 23 EPM1 patients from the biceps brachii (BB) of the dominant and the extensor digitorum communis (EDC) of the non-dominant arm for 48 hours. The patients self-reported the degree of myoclonus in a diary once an hour. Severity of myoclonus with action was evaluated by using video-recorded Unified Myoclonus Rating Scale (UMRS). Correlations of monitored parameters were quantified with the UMRS scores and the self-reported degrees of myoclonus.

Results: The monitoring-based myoclonus index correlated significantly (p < 0.001) with the UMRS scores (ρ = 0.883 for BB and ρ = 0.823 for EDC) and with the self-reported myoclonus degrees (ρ = 0.483 for BB and ρ = 0.443 for EDC). Ten patients were assessed as probably having negative myoclonus in UMRS, while our algorithm detected that in twelve patients.

Conclusions: Wearable monitoring was able to detect both positive and negative myoclonus in EPM1 patients.

Significance: Our method is suitable for quantifying objective, real-life treatment effects at home and progression of myoclonus.
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http://dx.doi.org/10.1016/j.clinph.2021.06.026DOI Listing
July 2021

Reperfusion therapies and in-hospital outcomes for ST-elevation myocardial infarction in Europe: the ACVC-EAPCI EORP STEMI Registry of the European Society of Cardiology.

Eur Heart J 2021 Aug 14. Epub 2021 Aug 14.

Spitalul Clinic de Urgenta "Floreasca", Calea Floreasca 8, București 014461, Romania.

Aims : The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI).

Methods And Results : Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset <24 h in 196 centres across 29 countries. A total of 11 462 patients were enrolled, for whom primary percutaneous coronary intervention (PCI) (total cohort frequency: 72.2%, country frequency range 0-100%), fibrinolysis (18.8%; 0-100%), and no reperfusion therapy (9.0%; 0-75%) were performed. Corresponding in-hospital mortality rates from any cause were 3.1%, 4.4%, and 14.1% and overall mortality was 4.4% (country range 2.5-5.9%). Achievement of quality indicators for reperfusion was reported for 92.7% (region range 84.8-97.5%) for the performance of reperfusion therapy of all patients with STEMI <12 h and 54.4% (region range 37.1-70.1%) for timely reperfusion.

Conclusions : The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality.
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http://dx.doi.org/10.1093/eurheartj/ehab342DOI Listing
August 2021

Epitranscriptomics of Ischemic Heart Disease-The IHD-EPITRAN Study Design and Objectives.

Int J Mol Sci 2021 Jun 21;22(12). Epub 2021 Jun 21.

Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland.

Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as -6-methyl-adenosine (mA) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on mA and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of mA and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.
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http://dx.doi.org/10.3390/ijms22126630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235045PMC
June 2021

Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction: The randomized, double-blind, placebo-controlled OXI pilot trial.

Int J Cardiol 2021 Aug 4;337:21-27. Epub 2021 May 4.

Heart and Lung Center, Helsinki University Hospital, Helsinki University, Helsinki, Finland. Electronic address:

Objectives: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction.

Method: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months.

Results: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to interruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups).

Conclusions: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocardial infarction.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.062DOI Listing
August 2021

Titanium-Nitride-Oxide-Coated Versus Everolimus-Eluting Stents in Acute Coronary Syndrome: The Randomized TIDES-ACS Trial.

JACC Cardiovasc Interv 2020 07;13(14):1697-1705

Heart Center, Satakunta Central Hospital, Pori, Finland; Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland.

Objectives: This study sought to compare next-generation cobalt-chromium-based titanium-nitride-oxide (TiNO)-coated stents with a platinum-chromium-based biodegradable polymer everolimus-eluting stent (EES) in patients with acute coronary syndrome (ACS).

Background: Previous generation TiNO-coated stents showed acceptable performance in patients with ACS.

Methods: In a multicenter, randomized trial, we randomly assigned 1,491 ACS patients (2:1) to receive either a TiNO-coated stent (n = 989) or EES (n = 502). The primary endpoint was the rate of a composite of cardiac death, myocardial infarction (MI), or ischemia-driven target lesion revascularization at 12-month follow-up. The co-primary endpoint was a composite of cardiac death, MI, or major bleeding at 18 months.

Results: A primary endpoint event occurred in 6.3% of patients in the TiNO-coated stent group versus in 7.0% in the EES group (hazard ratio: 0.93; 95% confidence interval: 0.71 to 1.22; p = 0.66 for superiority; p < 0.001 for noninferiority). A co-primary endpoint event occurred in 3.7% of the patients in the TiNO group and in 7.8% in the EES group (hazard ratio: 0.64; 95% confidence interval: 0.51 to 0.80; p = 0.001). TiNO-coated stents were associated with lower rates of cardiac death (0.6% vs. 2.6%; p = 0.002) and MI (2.2% vs. 5.0%; p = 0.007) at 18 months of follow-up. Rates of target lesion revascularization were not significantly different at 18 months (5.8% vs. 4.4%; p = 0.27).

Conclusions: In patients with ACS, cobalt-chromium-based TiNO-coated stents were noninferior to platinum-chromium-based biodegradable polymer EES for major cardiac events at 12 months, and were superior for the co-primary endpoint of cardiac death, MI, and bleeding at 18 months. (Comparison of Titanium-Nitride-Oxide-Coated Bio-Active-Stent (Optimax™) to the Drug (Everolimus) -Eluting Stent (Synergy™) in Acute Coronary Syndrome [TIDES-ACS]; NCT02049229).
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http://dx.doi.org/10.1016/j.jcin.2020.04.021DOI Listing
July 2020

Force-velocity profiling in ice hockey skating: reliability and validity of a simple, low-cost field method.

Sports Biomech 2020 Jun 17:1-16. Epub 2020 Jun 17.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

In recent years, a simple method for force-velocity (F-v) profiling, based on split times, has emerged as a potential tool to examine mechanical variables underlying running sprint performance in field conditions. In this study, the reliability and concurrent validity of F-v profiling based on split times were examined when used for ice hockey skating. It was also tested how a modification of the method, in which the start instant of the sprint is estimated based on optimisation (time shift method), affects the reliability and validity of the method. Both intra- and inter-rater reliability were markedly improved when using the time shift method (approximately 50% decrease in the standard error of measurement). Moreover, the results calculated using the time shift method highly correlated (r > 0.83 for all variables) with the results calculated from a continuously tracked movement of the athlete, which was considered here as the reference method. This study shows that a modification to the previously published simple method for F-v profiling improves intra- and inter-rater reliability of the method in ice hockey skating. The time shift method tested here can be used as a reliable tool to test a player's physical performance characteristic underlying sprint performance in ice hockey skating.
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http://dx.doi.org/10.1080/14763141.2020.1770321DOI Listing
June 2020

Nutritive sucking creates a neurophysiological bridge over the birth gap.

Acta Paediatr 2020 02 16;109(2):233-235. Epub 2019 Sep 16.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

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http://dx.doi.org/10.1111/apa.14993DOI Listing
February 2020

Magnesium 2000 postmarket evaluation: Guideline adherence and intraprocedural performance of a sirolimus-eluting resorbable magnesium scaffold.

Cardiovasc Revasc Med 2019 Dec 10;20(12):1140-1145. Epub 2019 Feb 10.

Unique Medical Centre, Kowloon, Hong Kong.

Background: The Magmaris bioresorbable magnesium scaffold was successfully tested in in-vitro and in clinical premarket studies. Subsequently the Magmaris postmarket program aimed to review intraprocedural data of at least 2000 patients to assess user preferences, guideline adherence and intraprocedural performance in clinical routine.

Methods: This international multicentre survey encompasses data from 356 hospitals across 45 countries. As part of the certification for Magmaris implantation, each hospital had to complete consecutive post-market evaluation forms of their first 10 commercial Magmaris patients.

Results: From June 2016 to May 2018, data on 2018 implantations were collected. Main reasons for selecting Magmaris was patients' life expectancy (67%, n = 1359) and low or not calcified lesions, (67%, n = 1357). Magmaris was successfully deployed in 99% of cases (n = 1995), predilatation was performed in 95% (n = 1922) and post-dilatation in 87% (n = 1756). Physicians rated the overall performance and the pushability as good or very good in 96% of cases (n = 1799). Guide wire friction, trackability, and conformability were rated as good or very good in 94% of cases, and crossability in 93%. The majority of patients were scheduled to receive dual antiplatelet therapy for up to 12 months.

Conclusion: Generally, implantation guidelines were adhered to and theoretical advantages of the metal scaffold observed in in-vitro tests have translated into practice with good intraprocedural performance outcomes, confirming the controlled roll-out of this novel technology into clinical practice.

Summary For Annotated Table Of Content: The Magmaris 2000 program includes the first commercial cases at each hospital. Overall, data on 2018 implantations were collected. The high rate of pre- and post-dilatation as well as other parameters confirm that generally the implantation guidelines are adhered to and the good intraprocedural performance (rated as good or very good in 96%) confirm the theoretical advantages of a metallic scaffold in practice.
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http://dx.doi.org/10.1016/j.carrev.2019.02.003DOI Listing
December 2019

Tooth Clenching Induces Abnormal Cerebrovascular Responses in Migraineurs.

Front Neurol 2018 21;9:1112. Epub 2018 Dec 21.

Institute of Dentistry, University of Eastern Finland, Kuopio, Finland.

Prevalence of masticatory parafunctions, such as tooth clenching and grinding, is higher among migraineurs than non-migraineurs, and masticatory dysfunctions may aggravate migraine. Migraine predisposes to cerebrovascular disturbances, possibly due to impaired autonomic vasoregulation, and sensitization of the trigeminovascular system. The relationships between clenching, migraine, and cerebral circulation are poorly understood. We used Near-Infrared Spectroscopy to investigate bilateral relative oxy- (%Δ[OHb]), deoxy- (%Δ[HHb]), and total (%Δ[tHb]) hemoglobin concentration changes in prefrontal cortex induced by maximal tooth clenching in twelve headache-free migraineurs and fourteen control subjects. From the start of the test, migraineurs showed a greater relative increase in right-side %Δ[HHb] than controls, who showed varying reactions, and right-side increase in %Δ[tHb] was also greater in migraineurs ( < 0.001 and < 0.05, respectively, time-group interactions, Linear mixed models). With multivariate regression model, migraine predicted the magnitude of maximal blood pressure increases, associated in migraineurs with mood scores and an intensity of both headache and painful signs of temporomandibular disorders (pTMD). Although changes in circulatory parameters predicted maximal NIRS responses, the between-group differences in the right-side NIRS findings remained significant after adjusting them for systolic blood pressure and heart rate. A family history of migraine, reported by all migraineurs and four controls, also predicted maximal increases in both %Δ[HHb] and %Δ[tHb]. Presence of pTMD, revealed in clinical oral examination in eight migraineurs and eight controls, was related to maximal %Δ[HHb] increase only in controls. To conclude, the greater prefrontal right-side increases in cerebral %Δ[HHb] and %Δ[tHb] may reflect disturbance of the tooth clenching-related cerebral (de)oxygenation based on impaired reactivity and abnormal microcirculation processes in migraineurs. This finding may have an impact in migraine pathophysiology and help to explain the deleterious effect of masticatory dysfunctions in migraine patients. However, the role of tooth clenching as a migraine trigger calls for further studies.
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http://dx.doi.org/10.3389/fneur.2018.01112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309104PMC
December 2018

An Overview of Strategies for Reducing Upper Extremity Physical Exposure Associated With Floor Mopping: A Systematic Review.

Hum Factors 2019 02 10;61(1):43-63. Epub 2018 Dec 10.

University of Eastern Finland, Kuopio.

Objective: This systematic review synthesizes literature on upper extremity physical exposure associated with floor mopping, in order to (a) assess the impact of changes in mopping systems on physical exposure and (b) propose recommendations for strategies to reduce exposure.

Background: Floor-cleaning tools and equipment have undergone major improvements. Existing studies have focused on mop design modifications and cleaning efficiency. However, less is known about strain responses caused by modern tools and methods.

Method: Studies from 1987 to February 2017 were identified by electronic and manual search. All selected studies underwent a quality assessment. The evidence was organized into categories representing different strategies for reducing exposure. The levels of evidence were determined using a best evidence synthesis approach.

Results: Eleven studies were included. Based on the review findings, currently there is moderate evidence suggesting that reduced physical exposure has been achieved through development of mopping systems. Levels of evidence for strategies associated with positive effects on physical exposure were: moderate evidence for mop design and handle type, insufficient evidence for mopping technique, and mixed evidence for mopping methods and environment modifications. Therefore, the present study suggests the use of adjustable mop handles as a strategy for reducing physical exposure.

Conclusion: A more comprehensive approach to reducing physical exposure concerning floor mopping work is necessary.

Application: Knowledge regarding physical exposure reduction can be applied as the basis for decision making in cleaning practice. Information can be incorporated into future research regarding development of floor-cleaning methods.
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http://dx.doi.org/10.1177/0018720818816261DOI Listing
February 2019

Parameters of Surface Electromyogram Suggest That Dry Immersion Relieves Motor Symptoms in Patients With Parkinsonism.

Front Neurosci 2018 26;12:667. Epub 2018 Sep 26.

Biosignal Analysis and Medical Imaging Group, Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, Kuopio, Finland.

Dry immersion (DI) is acknowledged as a reliable space flight analog condition. At DI, subject is immersed in water being wrapped in a waterproof film to imitate microgravity (μG). Microgravity is known to decrease muscle tone due to deprivation of the sensory stimuli that activate the reflexes that keep up the muscle tone. In contrary, parkinsonian patients are characterized by elevated muscle tone, or rigidity, along with rest tremor and akinesia. We hypothesized that DI can diminish the elevated muscle tone and/or the tremor in parkinsonian patients. Fourteen patients with Parkinson's disease (PD, 10 males, 4 females, 47-73 years) and 5 patients with vascular parkinsonism (VP, 1 male, 4 females, 65-72 years) participated in the study. To evaluate the effect of DI on muscles' functioning, we compared parameters of surface electromyogram (sEMG) measured before and after a single 45-min long immersion session. The sEMG recordings were made from the biceps brachii muscle, bilaterally. Each recording was repeated with the following loading conditions: with arms hanging freely down, and with 0, 1, and 2 kg loading on each hand with elbows flexed to 90°. The sEMG parameters comprised of amplitude, median frequency, time of decay of mutual information, sample entropy, correlation dimension, recurrence rate, and determinism of sEMG. These parameters have earlier been proved to be sensitive to PD severity. We used the Wilcoxon test to decide which parameters were statistically significantly different before and after the dry immersion. Accepting the < 0.05 significance level, amplitude, time of decay of mutual information, recurrence rate, and determinism tended to decrease, while median frequency and sample entropy of sEMG tended to increase after the DI. The most statistically significant change was for the determinism of sEMG from the left biceps with 1 kg loading, which decreased for 84% of the patients. The results suggest that DI can promptly relieve motor symptoms of parkinsonism. We conclude that DI has strong potential as a rehabilitation method for parkinsonian patients.
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http://dx.doi.org/10.3389/fnins.2018.00667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168649PMC
September 2018

Performance of CHADS-VASc score for stroke prediction after surgical aortic valve replacement.

J Thorac Cardiovasc Surg 2019 Mar 29;157(3):896-904. Epub 2018 Jul 29.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland; Department of Surgery, Oulu University Hospital, Oulu, Finland.

Objective: Stroke is a frequent complication occurring early and late after surgical aortic valve replacement. There is an unmet clinical need for simple tools to assess postoperative stroke risk. We sought to assess the predictive performance of Congestive heart failure; Hypertension; Age ≥75 (doubled); Diabetes mellitus; prior Stroke, transient ischemic attack or thromboembolism (doubled); Vascular disease; Age 65 to 74; Sex category (female) (CHADS-VASc) score in patients undergoing surgical aortic valve replacement with a bioprosthesis.

Methods: Seven hundred fourteen patients undergoing isolated surgical aortic valve replacement with a bioprosthesis at 4 university hospitals were included. Data were collected retrospectively from patient records and monitored by an independent party.

Results: Median follow-up time was 4.8 years. Mean CHADS-VASc score was 4.1 ± 1.6. Low (scores, 0-1), high (scores, 2-4), and very high (scores, 5-9) CHADS-VASc scores were observed in 39 (5.5%), 400 (56.0%), and 262 (38.5%) patients, respectively. Incidences of stroke or transient ischemic attack at 1 year were 2.6%, 4.8%, and 10.7%; at 5 years incidences were 5.2%, 14.0%, and 21.9%; and at 10 years incidence were 5.2%, 20.7%, and 37.9% for patients in low, high, and very high scores, respectively. Incidences of major bleeds at 1 year were 0%, 1.8%, and 2.7%; at 5 years incidences were 0%, 5.4%, and 8.7%; and at 10 years incidences were 0%, 9.0%, and 27.1%, respectively. Competing risk analysis showed that patients with CHADS-VASc score of 5 through 9 had a significantly increased risk of stroke or transient ischemic attack (hazard ratio, 4.75; 95% confidence interval, 1.09-20.6; P = .037) irrespective of preoperative or new-onset in-hospital atrial fibrillation compared with low-risk patients.

Conclusions: CHADS-VASc is a valuable tool to identify patients with increased risk of stroke and major bleeding, and for whom alternative strategies for prevention of late neurologic complications should be adopted.
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http://dx.doi.org/10.1016/j.jtcvs.2018.06.096DOI Listing
March 2019

Autonomic responses to tooth clenching in migraineurs-augmented trigeminocardiac reflex?

J Oral Rehabil 2018 Oct 3;45(10):764-769. Epub 2018 Aug 3.

Institute of Dentistry, University of Eastern Finland, Kuopio, Finland.

Background: Systemic autonomic changes are well known in migraineurs. Also, masticatory disorders are reported to be associated with migraine. However, if those phenomena are interrelated, and how, is unclear. Moreover, the knowledge on the autonomic responses to masticatory stimuli in migraineurs is limited.

Objective: To investigate tooth clenching-related cardiac autonomic regulation in migraineurs.

Methods: We compared maximal tooth clenching-induced systemic autonomic responses, indicated by heart rate variability and blood pressure changes, in headache-free migraineurs (n = 17) and control subjects (n = 22).

Results: Levels of high-frequency power, reflecting vagal activity, were lower in migraineurs at baseline but increased after tooth clenching whereas in controls they returned to baseline (P < 0.05, mixed model analysis). In multivariate regression model, the presence of migraine predicted the baseline levels of low- and high-frequency power and sympathovagal balance, and the post-test increase in high-frequency power, with the attack frequency and side of headache as the modifiers of the measured changes in migraineurs. The painful signs of temporomandibular disorders, found in clinical oral examination, enhanced both maximal changes in RR intervals and post-test vagal responses to tooth clenching only in migraineurs.

Conclusion: The enhanced post-clenching vagal activation may represent a marker of the augmented trigeminocardiac reflex to stimulation of trigeminal area, sensitised in migraineurs. Our results support an involvement of autonomic mechanisms in migraine pathophysiology and are interesting in terms of interactions between migraine and masticatory disorders, elucidating one potential way how masticatory disorders may aggravate migraine.
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http://dx.doi.org/10.1111/joor.12693DOI Listing
October 2018

In vivo morphologic comparison of saphenous vein grafts and native coronary arteries following non-ST elevation myocardial infarction.

Cardiovasc Revasc Med 2019 01 16;20(1):16-21. Epub 2018 Apr 16.

Sydney Medical School, Faculty of Medicine, The University of Sydney, Camperdown, NSW, Australia; Department of Cardiology, Royal North Shore Hospital, Sydney, Australia. Electronic address:

Objective: This study aimed to assess the pathophysiological differences between saphenous vein grafts (SVG) and native coronary arteries (NCA) following presentation with non-ST elevated myocardial infarction (NSTEMI).

Background: There is accelerated pathogenesis of de novo coronary disease in harvested SVG following coronary artery bypass (CABG) surgery, which contributes to both early and late graft failure, and is also causal in adverse outcomes following vein graft PCI. However in vivo assessment, with OCT imaging, comparing the differences between vein grafts and NCAs has not previously been performed.

Methods: We performed a retrospective, observational, analysis in patients who underwent PCI with adjunctive OCT imaging following presentation with NSTEMI, where the infarct-related artery (IRA) was either in an SVG or NCA.

Results: A total of 1550 OCT segments was analysed from thirty patients with a mean age of 66.3 (±9.0) years were included. The mean graft age of 13.9 (±5.6) years in the SVG group. OCT imaging showed that the SVG group had evidence of increased lipid pool burden (lipid pool quadrants, 2.1 vs 2.7; p = 0.021), with a reduced fibro-atheroma cap-thickness in the SVG group (45.0 μm vs 38.5 μm; p = 0.05) and increased burden of calcification (calcified lesion length = 0.4 mm vs 1.8 mm; p = 0.007; calcified quadrants = 0.2 vs 0.9; p = 0.001; arc of superficial calcium deposits = 11.6° vs 50.9°; p = 0.007) when compared to NCA.

Conclusion: This OCT study has demonstrated that vein grafts have a uniquely atherogenic environment which leads to the development of calcified, lipogenic, thin-capped fibro-atheroma's, which may be pivotal in the increased, acute and chronic graft failure rate, and may underpin the increased adverse outcomes following vein graft PCI.
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http://dx.doi.org/10.1016/j.carrev.2018.04.010DOI Listing
January 2019

Levodopa-Induced Changes in Electromyographic Patterns in Patients with Advanced Parkinson's Disease.

Front Neurol 2018 5;9:35. Epub 2018 Feb 5.

Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.

Levodopa medication is the most efficient treatment for motor symptoms of Parkinson's disease (PD). Levodopa significantly alleviates rigidity, rest tremor, and bradykinesia in PD. The severity of motor symptoms can be graded with UPDRS-III scale. Levodopa challenge test is routinely used to assess patients' eligibility to deep-brain stimulation (DBS) in PD. Feasible and objective measurements to assess motor symptoms of PD during levodopa challenge test would be helpful in unifying the treatment. Twelve patients with advanced PD who were candidates for DBS treatment were recruited to the study. Measurements were done in four phases before and after levodopa challenge test. Rest tremor and rigidity were evaluated using UPDRS-III score. Electromyographic (EMG) signals from biceps brachii and kinematic signals from forearm were recorded with wireless measurement setup. The patients performed two different tasks: arm isometric tension and arm passive flexion-extension. The electromyographic and the kinematic signals were analyzed with parametric, principal component, and spectrum-based approaches. The principal component approach for isometric tension EMG signals showed significant decline in characteristics related to PD during levodopa challenge test. The spectral approach on passive flexion-extension EMG signals showed a significant decrease on involuntary muscle activity during the levodopa challenge test. Both effects were stronger during the levodopa challenge test compared to that of patients' personal medication. There were no significant changes in the parametric approach for EMG and kinematic signals during the measurement. The results show that a wireless and wearable measurement and analysis can be used to study the effect of levodopa medication in advanced Parkinson's disease.
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http://dx.doi.org/10.3389/fneur.2018.00035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807331PMC
February 2018

Value of DAPT score to predict adverse outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention: A post-hoc analysis from the AFCAS registry.

Int J Cardiol 2018 02;253:35-39

Heart Center, Turku University Hospital, University of Turku, Turku, Finland. Electronic address:

Background: The DAPT score identifies patients with expected benefit from extended dual antiplatelet therapy beyond 1year after percutaneous coronary intervention (PCI). In a post-hoc analysis from the AFCAS registry, we explored the value of DAPT score to predict outcome in patients with atrial fibrillation (AF) undergoing PCI.

Methods And Results: Outcome measures included major adverse cardiac/cerebrovascular events (MACCE) [all-cause death, myocardial infarction, repeat revascularization, stent thrombosis, or stroke/transient ischemic attack] and bleeding events. At 12-month follow-up, patients with a DAPT score≥1 had a higher incidence of MACCE, all-cause death, myocardial infarction (p=0.004, p=0.006, and p=0.013, respectively), but a similar bleeding rate (p=0.66), versus those with a DAPT score <1. In a subgroup of patients at high risk of stroke who received triple therapy for 1month only, DAPT score ≥1 was associated with a higher incidence of MACCE, all-cause death, myocardial infarction (p=0.002, p=0.015, and p=0.039, respectively), but a similar bleeding rate (p=0.81).

Conclusions: In AF patients undergoing PCI, a DAPT score ≥1 was associated with a higher incidence of thrombotic events, and a similar incidence of bleeding events, compared with a DAPT score <1. These results were consistent in patients at high risk of stroke who received triple therapy for 1month.
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http://dx.doi.org/10.1016/j.ijcard.2017.07.074DOI Listing
February 2018

Outcome of octogenarians with atrial fibrillation undergoing percutaneous coronary intervention: insights from the AFCAS registry.

Clin Cardiol 2017 Dec 15;40(12):1264-1270. Epub 2017 Dec 15.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Background: More evidence is needed on the optimal antithrombotic regimen in elderly patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).

Hypothesis: Octogenarian patients (aged ≥80 years) with AF who underwent PCI have worse 12-month clinical outcome, compared with younger patients.

Methods: We performed a post-hoc analysis of data from the prospective, multicenter AFCAS registry, which enrolled consecutive patients with AF who underwent PCI and stenting. Outcome measures included major adverse cardiac/cerebrovascular events (MACCE; all-cause death, myocardial infarction, repeat revascularization, stent thrombosis, or stroke/transient ischemic attack) and bleeding events at 12-month follow-up.

Results: Out of 925 AF patients enrolled in AFCAS registry, 195 (21.1%) were ≥80 years. Mean age was 82.9 ± 2.6 years; 41.5% were women; 32.3% had diabetes mellitus. Compared with patients aged <80 years, there were more females among the octogenarians (P < 0.001). Compared with younger patients, octogenarians smoked and had dyslipidemia less often, and presented more frequently with acute coronary syndrome. The frequency and duration of antithrombotic regimens prescribed at discharge were comparable. At 12-month follow-up, overall MACCE rate was higher in octogenarians compared with younger patients (27.7% vs 20.1%, P = 0.02). The rate of acute myocardial infarction was higher in octogenarians (9.2% vs 4.9%, P = 0.02), but the rates of all bleeds and BARC >2 bleeds were similar (P = 0.13, P = 0.29, respectively).

Conclusions: In real-world patients with AF undergoing PCI, patients aged ≥80 years had higher incidence of MACCE at 12-month follow-up compared with younger patients, although they received comparable antithrombotic treatment. The rates of bleeding events were similar.
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http://dx.doi.org/10.1002/clc.22821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490386PMC
December 2017

Evaluation of the Effect of Bariatric Surgery-Induced Weight Loss on Knee Gait and Cartilage Degeneration.

J Biomech Eng 2018 04;140(4)

Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, Finland; Diagnostic Imaging Centre, Kuopio University Hospital, P.O. Box 100, Kuopio FI-70029, Finland e-mail: .

The objective of the study was to investigate the effects of bariatric surgery-induced weight loss on knee gait and cartilage degeneration in osteoarthritis (OA) by combining magnetic resonance imaging (MRI), gait analysis, finite element (FE) modeling, and cartilage degeneration algorithm. Gait analyses were performed for obese subjects before and one-year after the bariatric surgery. FE models were created before and after weight loss for those subjects who did not have severe tibio-femoral knee cartilage loss. Knee cartilage degenerations were predicted using an adaptive cartilage degeneration algorithm which is based on cumulative overloading of cartilage, leading to iteratively altered cartilage properties during OA. The average weight loss was 25.7±11.0 kg corresponding to a 9.2±3.9 kg/m2 decrease in body mass index (BMI). External knee rotation moment increased, and minimum knee flexion angle decreased significantly (p < 0.05) after weight loss. Moreover, weight loss decreased maximum cartilage degeneration by 5±23% and 13±11% on the medial and lateral tibial cartilage surfaces, respectively. Average degenerated volumes in the medial and lateral tibial cartilage decreased by 3±31% and 7±32%, respectively, after weight loss. However, increased degeneration levels could also be observed due to altered knee kinetics. The present results suggest that moderate weight loss changes knee kinetics and kinematics and can slow-down cartilage degeneration for certain patients. Simulation results also suggest that prediction of cartilage degeneration is subject-specific and highly depend on the altered gait loading, not just the patient's weight.
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http://dx.doi.org/10.1115/1.4038330DOI Listing
April 2018

Rapid cardiothoracic ultrasound protocol for diagnosis of acute heart failure in the emergency department.

Eur J Emerg Med 2019 Apr;26(2):112-117

Department of Cardiology, Pori Central Hospital, Pori, Finland.

Objectives: The aim of this study was to evaluate the performance of a rapid cardiothoracic ultrasound protocol (CaTUS), combining echocardiographically derived E/e' and lung ultrasound (LUS), for diagnosing acute heart failure (AHF) in patients with undifferentiated dyspnea in an emergency department (ED).

Patients And Results: We enrolled 100 patients with undifferentiated dyspnea from a tertiary care ED, who all had CaTUS done immediately upon arrival in the ED. CaTUS was positive for AHF with an E/e' > 15 and congestion, that is bilateral B-lines or bilateral pleural fluid, on LUS. In addition, an inferior vena cava index was also recorded to analyze whether including a central venous pressure estimate would add diagnostic benefit to the CaTUS protocol. All 100 patients had a brain natriuretic peptide (BNP) sample withdrawn, and 96 patients underwent chest radiography in the ED, which was analyzed later by a blinded radiologist. The reference diagnosis of AHF consisted of either a BNP of more than 400 ng/l or a BNP of less than 100 ng/l in combination with congestion on chest radiography and structural heart disease on conventional echocardiography.CaTUS had a sensitivity of 100% (95% confidence interval: 91.4-100%), a specificity of 95.8% (95% confidence interval: 84.6-99.3%), and an area under the curve of 0.979 for diagnosing AHF (P<0.001). The diagnostic accuracy of CaTUS was higher than of either E/e' or LUS alone. Adding the inferior vena cava index to CaTUS did not improve diagnostic accuracy. CaTUS seemed helpful also for differential diagnostics of dyspnea, mainly regarding pneumonias and pulmonary embolisms.

Conclusion: CaTUS, combining E/e' and LUS, provided excellent accuracy for diagnosing AHF.
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http://dx.doi.org/10.1097/MEJ.0000000000000499DOI Listing
April 2019

Focused echocardiography and lung ultrasound protocol for guiding treatment in acute heart failure.

ESC Heart Fail 2018 02 28;5(1):120-128. Epub 2017 Sep 28.

Heart and Lung Center, Helsinki University Hospital, Turku, Finland.

Aims: There is little evidence-based therapy existing for acute heart failure (AHF), hospitalizations are lengthy and expensive, and optimal monitoring of AHF patients during in-hospital treatment is poorly defined. We evaluated a rapid cardiothoracic ultrasound (CaTUS) protocol, combining focused echocardiographic evaluation of cardiac filling pressures, that is, medial E/e' and inferior vena cava index, with lung ultrasound (LUS) for guiding treatment in hospitalized AHF patients.

Methods And Results: We enrolled 20 consecutive patients hospitalized for AHF, whose in-hospital treatment was guided using the CaTUS protocol according to a pre-specified treatment protocol targeting resolution of pulmonary congestion on LUS and lowering cardiac filling pressures. Treatment results of these 20 patients were compared with those of a standard care sample of 100 patients, enrolled previously for follow-up purposes. The standard care sample had CaTUS performed daily for follow-up and received standard in-hospital treatment without ultrasound guidance. All CaTUS exams were performed by a single experienced sonographer. The CaTUS-guided therapy resulted in significantly larger decongestion as defined by reduction in symptoms, cardiac filling pressures, natriuretic peptides, cumulative fluid loss, and resolution of pulmonary congestion (P < 0.05 for all) despite a shorter mean length of hospitalization. Congestion parameters were significantly lower also at discharge (P < 0.05 for all), without any significant difference in these parameters on admission. The treatment arm displayed better survival regarding the combined endpoint of 6 month all-cause death or AHF re-hospitalization (log rank P = 0.017). No significant difference in adverse events occurred between the groups.

Conclusions: The CaTUS-guided therapy for AHF resulted in greater decongestion during shorter hospitalization without increased adverse events in this small pilot study and might be associated with a better post-discharge prognosis.
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http://dx.doi.org/10.1002/ehf2.12208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793966PMC
February 2018

Time in therapeutic range and major adverse outcomes in atrial fibrillation patients undergoing percutaneous coronary intervention: The Atrial Fibrillation Undergoing Coronary Artery Stenting (AFCAS) registry.

Am Heart J 2017 Aug 3;190:86-93. Epub 2017 Jun 3.

Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address:

Background: Combination of oral anticoagulation (OAC) and antiplatelets is used in atrial fibrillation (AF) patients undergoing percutaneous coronary intervention and stent (PCI-S) procedure but is associated with increased bleeding when triple antithrombotic therapy (TAT) is used. Our aim was to analyze the impact of time in therapeutic range (TTR) on outcomes, in patients prescribed with TAT.

Methods: Ancillary analysis from the AFCAS registry in patients assigned to TAT. TTR was calculated with Rosendaal method. Outcomes were analyzed according to TTR tertiles (T1 [≤56.8%] vs. T2 [56.9-93.8%] vs. T3 [≥93.9%]). Major bleeding was the primary outcome.

Results: Of 963 patients enrolled, 470(48.8%) were prescribed with TAT at discharge and qualified for this analysis. Median [IQR] TTR was 80.0% [45.3-100%]. After 359 [341-370] days, major bleeding rates were progressively lower with increasing TTR tertiles (T1 vs. T2 vs. T3: 10.3% vs. 4.7% vs. 2.3%, P=.006). Kaplan-Meier analysis demonstrated a progressively lower risk for major bleeding across tertiles (P=.006). Patients in the highest TTR tertile had a non-significant lower risk for major adverse coronary and cerebrovascular events (MACCE) (log-rank: 4.905, P=.086). Cox regression analysis showed that T2 and T3 were inversely associated with major bleeding (hazard ratio [HR]:0.39, P=.050 and HR: 0.21, P=.005). Continuous TTR was inversely associated with major bleeding (HR: 0.98, P<.001). For MACCE, adjusted Cox analysis found a non-significant lower risk for T3 (HR: 0.64, P=.128).

Conclusions: In AF patients undergoing PCI-S prescribed TAT, good quality anticoagulation control (as reflected by TTR) was closely related to bleeding outcomes during follow-up. Despite some suggestive trends for an inverse relationship between TTR and MACCE, no definitive conclusions can be drawn, and further large studies are needed.
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http://dx.doi.org/10.1016/j.ahj.2017.05.016DOI Listing
August 2017

Outcome of poor initial TIMI flow in patients presenting with acute coronary syndrome.

Scand Cardiovasc J 2017 Oct 30;51(5):248-254. Epub 2017 Jun 30.

a Heart Center , Satakunta Central Hospital , Pori , Finland.

Objectives: We explored the predictors and outcome of poor, versus good, initial TIMI flow in patients with acute coronary syndrome (ACS).

Design: We performed post-hoc analysis of a randomized trial of patients presenting with ACS who received 2 comparative stents. Poor initial TIMI flow was defined as baseline TIMI flow grade 0/1 at the initial coronary angiography. The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, non-fatal myocardial infarction or ischemia-driven target lesion revascularization. Stent thrombosis (ST) was adjudicated according to the criteria of definite ST described by the Academic Research Consortium. Propensity score-matched analysis was performed. We report data after 5-year follow-up.

Results: Of 827 patients enrolled, 279 (33.7%) had initial TIMI 0/1 flow. Median follow-up duration was 5.0 years. Presentation by ST-elevation myocardial infarction and target vessel other than left anterior descending artery predicted initial TIMI 0/1 flow. MACE rate was comparable between the 2 subgroups (14% versus 15.9%, in patients with poor versus good initial TIMI flow, respectively, p = .46). Individual endpoints were comparable (p > .05 for all). Definite ST was more frequent in patients with initial TIMI 0/1 flow (3.6% versus 1.5%, respectively, p = .048). This was driven by more frequent early events (30 days) (p = .036); late/very late events were comparable (p = 1.0).

Conclusions: Predictors of poor initial TIMI flow included presentation by ST-elevation myocardial infarction, and target vessel other than left anterior descending artery. Definite ST occurred more in patients with poor, versus good, initial TIMI flow, mainly driven by difference in early events.
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http://dx.doi.org/10.1080/14017431.2017.1346278DOI Listing
October 2017

Assessment of early treatment response by rapid cardiothoracic ultrasound in acute heart failure: Cardiac filling pressures, pulmonary congestion and mortality.

Eur Heart J Acute Cardiovasc Care 2018 Jun 9;7(4):311-320. Epub 2017 May 9.

4 Cardiology, University of Helsinki, Helsinki, Finland.

Background: It is unclear how to optimally monitor acute heart failure (AHF) patients. We evaluated the timely interplay of cardiac filling pressures, brain natriuretic peptides (BNPs), lung ultrasound (LUS) and symptoms during AHF treatment.

Methods: We enrolled 60 patients who had been hospitalised for AHF. Patients were examined with a rapid cardiothoracic ultrasound (CaTUS) protocol, combining LUS and focused echocardiographic evaluation of cardiac filling pressures (i.e. medial E/e' and inferior vena cava index [IVCi]). CaTUS was done at 0, 12, 24 and 48 hours (±3 hours) and on the day of discharge, alongside clinical evaluation and laboratory samples. Patients free of congestion (B lines or pleural fluid) on LUS at discharge were categorised as responders, whereas the rest were categorised as non-responders. Improvement in congestion parameters was evaluated separately in these groups. The effect of congestion parameters on prognosis was also analysed.

Results: Responders experienced a significantly larger decline in E/e' (2.58 vs. 0.38, p = 0.037) and dyspnoea visual analogue scale (1-10) score (7.68 vs. 3.57, p = 0.007) during the first 12 hours of treatment, while IVCi and BNPs declined later without no such rapid initial decline. Among patients experiencing a >3 U decline in E/e' during the first 12 hours of treatment, 18/21 were to become responders ( p < 0.001). LUS response was the only congestion parameter independently predicting both 6-month survival regarding all-cause mortality and the composite endpoint of all-cause mortality or rehospitalisation for AHF.

Conclusion: E/e' seemed like the most useful congestion parameter for monitoring early treatment response, predicting prognostically beneficial resolution of pulmonary congestion.
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http://dx.doi.org/10.1177/2048872617708974DOI Listing
June 2018

Neointimal Healing Evaluated by Optical Coherence Tomography after Drug-Eluting Absorbable Metal Scaffold Implantation in de novo Native Coronary Lesions: Rationale and Design of the Magmaris-OCT Study.

Cardiology 2017;137(4):225-230. Epub 2017 May 4.

Heart Center, Satakunta Central Hospital, Pori, Finland.

Objectives: We sought to explore neointimal healing assessed by optical coherence tomography (OCT) following implantation of the Magmaris sirolimus-eluting absorbable metal scaffold.

Methods: The Magmaris-OCT is a prospective, multicenter, single-arm observational clinical study, intended to enrol 60 consecutive patients with up to 2 de novo native coronary lesions, each located in different major epicardial vessels, with a reference vessel diameter of 2.5-3.5 mm, and a maximum lesion length of 20 mm. Patients will undergo Magmaris scaffold implantation in the target lesion, according to the standard practice. Clinical follow-up will take place at 30 days, and at 3, 6, 9, and 12 months. For invasive-imaging follow-up, patients will be classified into 3 groups: cohort A will be scheduled for follow-up at 3 months, cohort B at 6 months, and cohort C at 12 months. Invasive imaging will include quantitative coronary angiography, OCT evaluation, and coronary flow reserve measurement. The primary end point will be the percentage of uncovered scaffold struts assessed by OCT at the prespecified follow-up.

Conclusions: This study will provide insight into the short- and mid-term healing properties following Magmaris scaffold implantation, with special emphasis on the neointimal coverage of scaffold struts.
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http://dx.doi.org/10.1159/000468979DOI Listing
August 2018

Percutaneous revascularization of coronary chronic total occlusion: Toward a reappraisal of the available evidence.

J Cardiol 2017 Jun 18;69(6):799-807. Epub 2017 Mar 18.

Heart Center, Satakunta Central Hospital, Pori, Finland.

Chronic total occlusion (CTO) is a challenging subset of coronary artery disease that is commonly encountered in real-world practice; it is associated with worse long-term prognosis. Observational studies suggest that percutaneous coronary intervention (PCI) for CTO is associated with reduction in myocardial ischemia and improvement in quality of life and left ventricular function. Some observational studies suggested that CTO-PCI is associated with improvement of the 'hard' clinical endpoints; others did not. Nearly all these studies compared the clinical outcome of successful versus failed PCI, rather than comparing the outcome of a whole CTO-PCI cohort versus a 'true' control group. Interestingly, in observational studies that compared the outcome of CTO-PCI versus optimal medical treatment, long-term mortality was comparable between the two strategies. In patients with multi-vessel disease and CTO, complete revascularization is more often achieved by coronary artery bypass grafting than by PCI; the SYNTAX score of these patients often favors surgical revascularization according to the current guidelines. The current guidelines reflect the divergence of opinion on the usefulness/benefit of CTO-PCI, mainly due to the lack of randomized trials. Evidence is awaited from three ongoing randomized controlled trials comparing PCI versus optimal medical treatment in the setting of CTO.
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http://dx.doi.org/10.1016/j.jjcc.2016.12.006DOI Listing
June 2017

The REMEDEE-OCT Study: An Evaluation of the Bioengineered COMBO Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Coronary Stent Compared With a Cobalt-Chromium Everolimus-Eluting Stent in Patients With Acute Coronary Syndromes: Insights From Optical Coherence Tomography Imaging Analysis.

JACC Cardiovasc Interv 2017 03;10(5):489-499

Department of Cardiology, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany; Deutsches Zentrum für Herz- und Kreislaufforschung (DZHK), Berlin, Germany. Electronic address:

Objectives: The aim of the present study was to evaluate vascular healing of the bioengineered COMBO Dual Therapy Stent compared with a cobalt-chromium (CoCr) everolimus-eluting stent (EES) as assessed by optical coherence tomography in patients with acute coronary syndromes.

Background: CD34+ cells promote endothelial repair after vascular injury. The bioengineered COMBO Dual Therapy Stent combines CD34+ cell-capturing technology with abluminal sirolimus release, but more data from clinical studies evaluating the vascular response are needed.

Methods: In a prospective randomized multicenter clinical trial, 60 patients with acute coronary syndromes were randomized 1:1 to COMBO or CoCr EES implantation. The primary endpoint was the percentage of uncovered stent struts per stent. Stent assessment by optical coherence tomography was performed at baseline and at 60 days, followed by independent core laboratory analysis.

Results: The percentage of uncovered struts per stent was higher with the COMBO than the CoCr EES at 60 days (median 14.7% vs. 7.7%; p = 0.04). However, no significant difference in uncovered stent struts was observed in the strut level-based analysis at 60 days, which also accounted for clustering (COMBO vs. CoCr EES; 13.6% vs. 6.9%; p = 0.09; generalized linear mixed models-adjusted analysis). Neointimal thickness at 60 days was lower with the COMBO compared with the CoCr EES (median 30.17 vs. 50.26 μm; p = 0.02; stent-level analysis). There were no significant differences in the frequency of major adverse cardiac events and each component of major adverse cardiac events within the study population between the 2 groups at 30, 60, 180, 360, and 540 days post-procedure. No target vessel stent thrombosis has been documented within 540 days.

Conclusions: The present multicenter, prospective clinical study for the first time compared the vascular response of the bioengineered COMBO Dual Therapy Stent with a CoCr EES in patients early after acute coronary syndrome by using intracoronary optical coherence tomographic analysis. The percentage of uncovered stent struts per stent was somewhat higher after COMBO versus CoCr EES implantation as detected by optical coherence tomography, associated with reduced neointimal thickness.
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http://dx.doi.org/10.1016/j.jcin.2016.11.040DOI Listing
March 2017

Renal sympathetic denervation for treatment of patients with heart failure: summary of the available evidence.

Ann Med 2017 08 10;49(5):384-395. Epub 2017 Feb 10.

a Heart Center, Satakunta Central Hospital , Pori , Finland.

Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF. This provided the rationale for trials that demonstrated survival benefit associated with the use of beta adrenergic blockers in heart failure with reduced ejection fraction. Nevertheless, the MOXCON trial demonstrated that rapid uptitration of moxonidine (inhibitor of central sympathetic outflow) in patients with heart failure was associated with excess mortality and morbidity, despite reduction of plasma norepinephrine. Interestingly, renal norepinephrine spillover was the only independent predictor of adverse outcome in patients with heart failure, in multivariable analysis. Recently, renal sympathetic denervation has emerged as a novel approach for control of blood pressure in patients with treatment-resistant hypertension. This article summarizes the available evidence for the effect of renal sympathetic denervation in the setting of heart failure. Key messages Experimental studies supported a beneficial effect of renal sympathetic denervation in heart failure with reduced ejection fraction. Clinical studies demonstrated improvement of symptoms, and left ventricular function. In heart failure and preserved ejection fraction, renal sympathetic denervation is associated with improvement of surrogate endpoints.
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http://dx.doi.org/10.1080/07853890.2017.1282168DOI Listing
August 2017

Synergic impact of oral anticoagulation control and renal function in determining major adverse events in atrial fibrillation patients undergoing percutaneous coronary intervention: insights from the AFCAS registry.

Clin Res Cardiol 2017 Jun 11;106(6):420-427. Epub 2017 Jan 11.

University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Dudley Road, Birmingham, B18 7QH, UK.

Background: In patients with atrial fibrillation (AF), quality of oral anticoagulation control as well as impaired renal function are associated with adverse outcomes. Our objective was to analyze if there was a synergistic impact of these factors in determining adverse outcomes in AF patients undergoing percutaneous coronary intervention and stent (PCI-S).

Methods: Post-hoc analysis from the Atrial Fibrillation Undergoing Coronary Artery Stenting (AFCAS) registry. Poor oral anticoagulation control was defined as time in therapeutic range (TTR) <65%, while impaired renal function as creatinine clearance (CrCl) <60 ml/min.

Results: Of the whole cohort, 448 were eligible for this post-hoc analysis. Of these, 27.9% had TTR <65%only (Group I), 19.2% had CrCl <60 ml/min only (Group II), while 13.8% had both conditions (Group III). At follow-up, patients in Group III had a higher rate of major adverse cardiovascular and cerebrovascular events (MACCE) (p = 0.007), while patients in Groups I and III had higher rates of major bleeding. Kaplan-Meier analyses showed that patients in Group III had higher risk for MACCE (LogRank: 14.406, p = 0.003), while Group I and Group III patients had higher risk for major bleeding (LogRank: 12.290, p = 0.006). On Cox regression, presence of both conditions independently increased MACCE risk (p = 0.001), while TTR <65% alone and the presence of both conditions were independently associated with major bleeding (p = 0.004 and p = 0.028, respectively).

Conclusions: There was a synergic impact of oral anticoagulation control and renal function in determining major adverse events in AF patients undergoing PCI-S. Use of poor anticoagulation control and impaired renal function in combination would help identify AF patients undergoing PCI-S at risk for MACCE and/or major bleeding.
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http://dx.doi.org/10.1007/s00392-016-1071-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442242PMC
June 2017
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