Validation of 3D echocardiographic volume detection of left atrium by human cadaveric casts

Background: Left atrial volume is a prognostic factor in cardiac pathologies. We aimed to validate left atrial volume detection with 3D and 2D echocardiography (3DE and 2DE) by human cadaveric casts. 3DE facilitates measurement of atrial volume without geometrical assumptions or dependence on imaging angle in contrast to 2DE methods. Methods: For method validation, six water-filled balloons were submerged in a 20-l water tank and their volumes were measured with 3DE. Seven human cadaveric left atrial casts were prepared of silicone and were transformed into ultrasound-permeable casts. Casts were imaged in the same setting, so that 3DE and 2DE of casts represented transthoracic apical view. Left ventricle analysis softwares GE 4D Auto LVQ and TomTec 4D LV-Function were used for 3DE volumetry. Results; Balloon volumes ranged 37 to 255ml (mean 126 ml). 3DE resulted in an excellent volumetric agreement with balloon volumes, absolute bias was -3.7 ml (95% CI -5.9 to -1.4). Atrial cast volumes were 38 to 94 ml (mean 56.6 ml). 3DE and 2DE volumes were excellently correlated with cast volumes (r = 0.96 to 0.99). Biases were for GE 4D LVQ - 0.7 ml (95% CI -6.1 to 4.6), TomTec 4D LV-Function 3.3 ml (-1.9 to 8.5) and 2DE 2.9 ml (-4.0 to 9.9). 3DE resulted in lower limits of agreement and showed no volume-related bias in contrast to area-length method. Conclusions: We conclude that measurement of human cadaveric left atrial cast volumes by 3DE is in excellent agreement with true cast volumes.Peer reviewe

Medication adherence/persistence among patients with active multiple sclerosis in Finland

Objectives To explore adherence, persistence, and treatment patterns in patients with multiple sclerosis (MS) in Finland treated with disease-modifying therapies (DMTs) for active MS in 2005-2018. Materials and Methods The study cohort was identified using the Drug Prescription Register of Social Insurance Institute, Finland. All patients had at least one prescription of glatiramer acetate (GA), beta-interferons, teriflunomide, or delayed-release dimethyl fumarate (DMF). Adherence was calculated using proportion of days covered (PDC) (cutoff >= 0.8). Time to non-persistence was calculated by the number of days on index DMT treatment before the first treatment gap (>= 90 days) or switch and analyzed with time-to-event methodology. Results The cohort included 7474 MS patients (72.2% female; mean age 38.9 years). Treatment switches were steady over 2005-2012, peaked in 2015. PDC means (standard deviations) were GA, 0.87 (0.17); beta-interferons, 0.88 (0.15); DMF, 0.89 (0.14); teriflunomide, 0.93 (0.10). Adherence frequencies were GA, 78.4%; beta-interferons, 81.3%; DMF, 86.9%; teriflunomide, 91.7%. Logistic regression showed that age group, DMT and the starting year, sex, and hospital district independently affected adherence. Patients receiving teriflunomide and DMF, males, and older patients were more likely to persist on treatment. There was no difference in persistence between patients prescribed teriflunomide and DMF, or between GA and beta-interferons. Conclusions Oral DMTs had greater adherence and persistence than injectable DMTs.Peer reviewe

MRI-derived cardiac washout is slowed in the left ventricle and associated with left ventricular non-compaction in young patients with cryptogenic ischemic stroke

To elucidate underlying disease mechanisms, we compared transition of gadolinium-based contrast agent bolus in cardiac chambers in magnetic resonance imaging between young patents with cryptogenic ischemic stroke and stroke-free controls. We included 30 patients aged 18-50 years with cryptogenic ischemic stroke from the prospective Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers and Outcome (NCT01934725) study and 30 age- and gender-matched stroke-free controls. Dynamic contrast-enhanced T1-weighted first-pass perfusion images were acquired at 1.5 T and analyzed for transit time variables, area under curves, relative blood flow, and maximum and minimum enhancement rates in left atrial appendage, left atrium, and left ventricle. These data were compared with previously published left ventricular non-compaction data of the same study population. Arrival time of contrast agent bolus in superior vena cava was similar in patients and controls (6.7[2.0] vs. 7.1[2.5] cardiac cycles, P = 0.626). Arrival and peak times showed comparable characteristics in patients and controls (P > 0.535). The minimum enhancement rate of the left ventricle was lower in patients than in controls (- 28 +/- 11 vs. - 36 +/- 13 1/(cardiac cycle), P = 0.012). Area under curves, relative blood flow, and other enhancement rates showed no significant differences between patients and controls (P > 0.107). Relative blood flow of cardiac chambers correlated with non-compacted left ventricular volume ratio (P < 0.011). Our results indicate slower washout of contrast agent and blood flow stagnation in the left ventricle of young patients with cryptogenic ischemic stroke. The washout was associated with left ventricular non-compaction, suggesting conditions favoring formation of intraventricular thrombosis.Peer reviewe

Evidence of subtle left ventricular systolic dysfunction in cryptogenic stroke in the young

Introduction: Ischemic stroke in young patients often remains cryptogenic, that is, no underlying reason can be found. Some of these strokes may originate in the heart. Left ventricular (LV) dynamic volumetry and strain analysis are relatively new and promising methods for evaluating LV function. Methods: In this pilot study, we recruited 30 young (18-50 years) patients with cryptogenic ischemic stroke and 30 age- and sex-matched controls from the SECRETO study (NCT01934725). The LV systolic function was assessed by LV volumetry (ejection fraction, peak emptying rate, and time to peak emptying rate). The longitudinal systolic function was assessed by speckle tracking strain and strain rate imaging, and by tissue velocity imaging derived MAD (mitral annular displacement) and septal S'. Results: Stroke patients had less vigorous global longitudinal strain (median -18.9, interquartile range 3.3), compared to healthy controls (median -20.0, interquartile range 2.8), P = .010. There was no statistically significant differences in septal S', MAD, global longitudinal strain rate, or dynamic volumetry-derived parameters between the two groups. Conclusions: Young cryptogenic stroke patients have subtly altered systolic function compared to healthy controls, found merely with longitudinal strain analysis. This infers that the heart may play a role in the pathogenesis of cryptogenic ischemic stroke.Peer reviewe

Diastolic function in young patients with cryptogenic stroke : A case-control pilot study

Background Ischaemic stroke in young individuals often remains cryptogenic. In this pilot study, we investigated, whether advanced echocardiography methods could find differences in the diastolic function between young cryptogenic stroke patients and stroke-free controls. Methods We recruited 30 cryptogenic ischaemic stroke patients aged 18-49 and 30 age- and sex-matched stroke-free controls among participants of the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study (NCT01934725). We measured diastolic function parameters derived from speckle tracking strain rate, Doppler techniques and 4D volumetry. We also performed statistical analyses comparing only the highest and lowest tertile of cases and controls for each parameter. Results None of our patients or controls had diastolic dysfunction according to ASE/EACVI criteria. However, compared to stroke-free controls, the stroke patient group had lower E/A ratio of mitral inflow, lower lateral and mean e', lower A/a' ratio, lower strain rate in early diastole and lower speckle tracking-derived e/a ratio. When comparing the lowest tertiles, patients also had a lower peak filling rate by 4D volumetry, a lower peak early filling fraction (fraction of left ventricular filling during early diastole), and lower velocities in a series of the tissue Doppler-derived diastolic parameters and blood flow/tissue velocity ratios. Conclusion Our study displayed subtle differences in diastolic function between patients and stroke-free controls, which may play a role in early-onset cryptogenic stroke. The differences were clearer when the lowest tertiles were compared, suggesting that there is a subgroup of young cryptogenic stroke patients with subclinical heart disease.Peer reviewe

Left ventricular non-compaction as a potential source for cryptogenic ischemic stroke in the young : A case-control study

Background Up to 50% of ischemic strokes in the young after thorough diagnostic work-up remain cryptogenic or associated with low-risk sources of cardioembolism such as patent foramen ovale (PFO). We studied with cardiac magnetic resonance (CMR) imaging, whether left ventricular (LV) non-compaction-a possible source for embolic stroke due to sluggish blood flow in deep intertrabecular recesses-is associated with cryptogenic strokes in the young. Methods Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is an international prospective multicenter case-control study of young adults (aged 18-49 years) presenting with an imaging-positive first-ever ischemic stroke of undetermined etiology. In this pilot substudy, 30 cases and 30 age- and sex-matched stroke-free controls were examined with CMR. Transcranial Doppler (TCD) bubble test was performed to evaluate the presence and magnitude of right-to-left shunt (RLS). Results There were no significant differences in LV volumes, masses or systolic function between cases and controls; none of the participants had non-compaction cardiomyopathy. Semi-automated assessment of LV non-compaction was highly reproducible. Non-compacted LV mass (median 14.0 [interquartile range 12.6-16.0] g/m(2)vs. 12.7 [10.4-16.6] g/m(2), p = 0.045), the ratio of non-compacted to compacted LV mass (mean 25.6 +/- 4.2% vs. 22.8 +/- 6.0%, p = 0.015) and the percentage of non-compacted LV volume (mean 17.6 +/- 2.9% vs. 15.7 +/- 3.8%, p = 0.004) were higher in cases compared to controls. In a multivariate conditional logistic regression model including non-compacted LV volume, RLS and body mass index, the percentage of non-compacted LV volume (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.10-2.18, p = 0.011) and the presence of RLS (OR 11.94, 95% CI 1.14-124.94, p = 0.038) were independently associated with cryptogenic ischemic stroke. Conclusions LV non-compaction is associated with a heightened risk of cryptogenic ischemic stroke in young adults, independent of concomitant RLS and in the absence of cardiomyopathy.Peer reviewe

Right atrium and cryptogenic ischaemic stroke in the young : A case-control study

Publisher Copyright: © 2021 BMJ Publishing Group. All rights reserved.Background Recent studies suggest left atrial (LA) dysfunction in cryptogenic stroke. We studied the dynamics of right atrium (RA) and right atrial appendage (RAA) in young adults with cryptogenic stroke. We hypothesised that bi-atrial dysfunction and blood stagnation might contribute to thrombosis formation in patients with patent foramen ovale (PFO), as deep venous thrombosis is detected only in the minority of patients. Methods Thirty patients (aged 18-49) with a first-ever cryptogenic stroke and 30 age-matched and sex-matched stroke-free controls underwent cardiac magnetic resonance (CMR) imaging. An approach to estimate the RAA volume was developed, using crista terminalis and pectinate muscles as anatomical landmarks. Atrial expansion indices were calculated as (maximal volume - minimal volume) ×100%/minimal volume. Total pulmonary to systemic blood flow ratio (Qp/Qs) was based on phase contrast CMR. Right-to-left shunt (RLS) was evaluated with transoesophageal echocardiography in 29 patients and transcranial Doppler in 30 controls, moderate-to-severe RLS considered as clinically significant. Results We found that RA and RAA volumes were similar between patients and controls. Also, RA expansion index was similar, but RAA (95.6%±21.6% vs 108.7%±25.8%, p=0.026) and LA (126.2%±28% vs 144.9%±36.3%, p=0.023) expansion indices were lower in patients compared with controls. Seven (24%) of 29 patients had an RLS compared with 1 (3%) of 30 controls (p=0.012). Among 59 study subjects, RLS was associated with lower RA (81.9%±15.9% vs 98.5%±29.5%, p=0.030), RAA (84.7%±18% vs 105.6%±24.1%, p=0.022), LA (109.8%±18.6% vs 140.1%±33.7%, p=0.017) and LAA (median 102.9% (IQR 65.6%-121.7%) vs 229.1% (151.8%-337.5%], p=0.002) expansion indices and lower Qp/Qs ratio (0.91±0.06 vs 0.98±0.07, p=0.027). Conclusions This study suggests bi-atrial dysfunction in young adults with cryptogenic stroke, associated with moderate-to-severe RLS. Dysfunction of the atria and atrial appendages may be an additional mechanism for PFO-related stroke. Trial registration number NCT01934725.Peer reviewe

Medication adherence/persistence among patients with active multiple sclerosis in Finland

Objectives To explore adherence, persistence, and treatment patterns in patients with multiple sclerosis (MS) in Finland treated with disease-modifying therapies (DMTs) for active MS in 2005-2018. Materials and Methods The study cohort was identified using the Drug Prescription Register of Social Insurance Institute, Finland. All patients had at least one prescription of glatiramer acetate (GA), beta-interferons, teriflunomide, or delayed-release dimethyl fumarate (DMF). Adherence was calculated using proportion of days covered (PDC) (cutoff >= 0.8). Time to non-persistence was calculated by the number of days on index DMT treatment before the first treatment gap (>= 90 days) or switch and analyzed with time-to-event methodology. Results The cohort included 7474 MS patients (72.2% female; mean age 38.9 years). Treatment switches were steady over 2005-2012, peaked in 2015. PDC means (standard deviations) were GA, 0.87 (0.17); beta-interferons, 0.88 (0.15); DMF, 0.89 (0.14); teriflunomide, 0.93 (0.10). Adherence frequencies were GA, 78.4%; beta-interferons, 81.3%; DMF, 86.9%; teriflunomide, 91.7%. Logistic regression showed that age group, DMT and the starting year, sex, and hospital district independently affected adherence. Patients receiving teriflunomide and DMF, males, and older patients were more likely to persist on treatment. There was no difference in persistence between patients prescribed teriflunomide and DMF, or between GA and beta-interferons. Conclusions Oral DMTs had greater adherence and persistence than injectable DMTs.</div

Revisiting left atrial volumetry by magnetic resonance imaging : the role of atrial shape and 3D angle between left ventricular and left atrial axis

Background Accurate measurement of left atrial (LA) volumes is needed in cardiac diagnostics and the follow up of heart and valvular diseases. Geometrical assumptions with 2D methods for LA volume estimation contribute to volume misestimation. In this study, we test agreement of 3D and 2D methods of LA volume detection and explore contribution of 3D LA axis orientation and LA shape in introducing error in 2D methods by cardiovascular magnetic resonance imaging. Methods 30 patients with prior first-ever ischemic stroke and no known heart disease, and 30 healthy controls were enrolled (age 18-49) in a substudy of a prospective case-control study. All study subjects underwent cardiac magnetic resonance imaging and were pooled for this methodological study. LA volumes were calculated by biplane area-length method from both conventional long axis (LAV(AL-LV)) and LA long axis-oriented images (LAV(AL-LA)) and were compared to 3D segmented LA volume (LAV(SAX)) to assess accuracy of volume detection. 3D orientation of LA long axis to left ventricular (LV) long axis and to four-chamber plane were determined, and LA 3D sphericity indices were calculated to assess sources of error in LA volume calculation. Shapiro-Wilk test, Bland-Altman analysis, intraclass and Pearson correlation, and Spearman's rho were used for statistical analysis. Results Biases were - 9.9 mL (- 12.5 to - 7.2) for LAV(AL-LV) and 13.4 (10.0-16.9) for LAV(AL-LA) [mean difference to LAV(SAX) (95% confidence interval)]. End-diastolic LA long axis 3D deviation angle to LV long axis was 28.3 +/- 6.2 degrees [mean +/- SD] and LA long axis 3D rotation angle to four-chamber plane 20.5 +/- 18.0 degrees. 3D orientation of LA axis or 3D sphericity were not correlated to error in LA volume calculation. Conclusions Calculated LA volume accuracy did not improve by using LA long axis-oriented images for volume calculation in comparison to conventional method. We present novel data on LA axis orientation and a novel metric of LA sphericity and conclude that these measures cannot be utilized to assess error in LA volume calculation.Peer reviewe

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

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 in-terruption 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 myocar-dial infarction. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe