Publications by authors named "Jouni Kuusisto"

8 Publications

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

Open Heart 2021 05;8(1)

Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center, Helsinki, Finland.

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.
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http://dx.doi.org/10.1136/openhrt-2021-001596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137166PMC
May 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

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

Echocardiography 2021 02 23;38(2):271-279. Epub 2021 Jan 23.

HUS Medical Imaging Center, Clinical Physiology and Nuclear Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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.
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http://dx.doi.org/10.1111/echo.14978DOI Listing
February 2021

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

PLoS One 2020 14;15(8):e0237228. Epub 2020 Aug 14.

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

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/m2 vs. 12.7 [10.4-16.6] g/m2, 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.

Clinical Trial Registration: SECRETO; NCT01934725. Registered 4th September 2013. https://clinicaltrials.gov/ct2/show/NCT01934725.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237228PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428175PMC
October 2020

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

Clin Physiol Funct Imaging 2020 Sep 4;40(5):336-342. Epub 2020 Jun 4.

Clinical Neurosciences, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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.
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http://dx.doi.org/10.1111/cpf.12640DOI Listing
September 2020

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

BMC Med Imaging 2018 11 15;18(1):43. Epub 2018 Nov 15.

Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Meilahti Tower Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki, Finland.

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 255 ml (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.
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http://dx.doi.org/10.1186/s12880-018-0282-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238356PMC
November 2018

The Accuracy of Left Ventricular and Left Atrial Volumetry Using 64-Slice Computed Tomography: In Vitro Validation Study With Human Cardiac Cadaveric Casts.

J Comput Assist Tomogr 2018 Sep/Oct;42(5):754-759

Division of Cardiology, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki.

Objective: We aimed to validate the accuracy of imaging of left atrial and ventricular volumes using cardiac cadaveric silicone casts.

Methods: Left atrial (n = 14) and ventricular (n = 15) casts were imaged using 64-slice computed tomography (CT). Water displacement (WD) of cardiac casts was used as the gold standard for volume measurements.

Results: Compared with WD, CT resulted in slightly higher left atrial and ventricular volumes (54 ± 25 vs 56 ± 26 mL [P = 0.003] and 57 ± 47 vs 66 ± 47 mL [P = 0.0001]). Variability between left atrial and ventricular volumes by CT and WD was low (coefficients of variation [CVs], 4% [intraclass correlation coefficient {ICC}, 0.99] and 12% [ICC, 0.97]). Intraobserver variability of CT was low for both the left atrium and the left ventricle (CVs, 1% [ICC, 1.00] and 4% [ICC, 1.00]).

Conclusions: Cardiac CT is both accurate and reproducible in assessment of left ventricular and atrial chamber volumes.
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http://dx.doi.org/10.1097/RCT.0000000000000773DOI Listing
September 2018

High-resolution signal-averaged analysis of atrial electromagnetic characteristics in patients with paroxysmal lone atrial fibrillation.

Ann Noninvasive Electrocardiol 2008 Oct;13(4):378-85

Department of Cardiology, Helsinki University Central Hospital, Department of Cardiology, Helsinki, Finland.

Background: Abnormalities in the electromagnetic signal of the atria during sinus rhythm could serve as markers of triggering foci or substrate for atrial fibrillation (AF). We examined atrial electrophysiologic properties noninvasively by using magnetocardiographic mapping (MCG) in patients with paroxysmal lone AF to find whether any difference exists between those who have frequent triggers of AF and who don't.

Methods: MCG was recorded over anterior chest during sinus rhythm in 80 patients with paroxysmal lone AF (44 +/- 12 years, 61 males) and 80 matched controls. Atrial wave duration (Pd) and root mean square amplitudes of the last 40 ms (RMS40) of the averaged filtered atrial complex were determined automatically. Patients expressing atrial arrhythmias triggering AF episodes were classified as focal AF.

Results: The Pd was 109 ms in patients and 104 ms in controls (P = 0.007). In focal AF (72%) the Pd was slightly prolonged and its proportion of the PR interval was larger, but RMS40 was normal compared to controls. In other patients, the Pd was close to controls, but the RMS40 was reduced (59 +/- 17 vs74 +/- 36 fT, P = 0.006). Pd and atrial RMS amplitudes were unrelated to duration of AF history or frequency of recurrences.

Conclusion: Clinical subclasses of lone AF seem to possess distinct signal profiles of atrial depolarization. Differences in electrophysiological properties between these subclasses may reflect pathogenetic variation and could have implications on diagnostics and therapy.
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http://dx.doi.org/10.1111/j.1542-474X.2008.00255.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932534PMC
October 2008
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