A method for measuring the angle between left atrial and left ventricular long axes using 3D echocardiography.

BACKGROUND: Left ventricle (LV) optimized views are routinely used for left atrial (LA) volume and strain measurements on 2D echocardiography. This might be a source of the error because of the variation of the angle between the left atrial and left ventricle long axes (LA-LV angle), leading to foreshortening of the LA. METHODS: We investigated two novel parameters: the angle between the left atrial and left ventricle long axes (LA-LV angle) and its deviation from the 4-chamber plane. To accurately measure the angles in 3D space, these measurements were performed using 3D echocardiography. We developed a method for the measurement based on marking anatomic points of reference in the 3D echocardiogram and measuring the angles between these points. We used three types of phantoms made of wood and agar-agar to investigate the repeatability and reproducibility of these measurements and performed measurements on human subjects. RESULTS: The ultrasound measurements were in excellent agreement with the true angles of the phantoms: LA-LV angle bias was .5 degrees (95% CI -1.8 to +2.7) in the wooden phantoms and 1.2 degrees (-.7 to +3.1) in the agar-agar phantoms, while the angle deviation from the 4-chamber plane was -.9 degrees (-4.3 to +4.1) in the wooden phantoms and .0 degrees (-3.3 to +3.3) in the agar-agar phantoms. The measurements demonstrated good repeatability and reproducibility (Pearson correlation coefficients ranging from .91 to .99). The measurements from human hearts showed good repeatability (Pearson correlation was .81 for repeated LA-LV angle measurements and .97 for repeated measurements of the deviation from the 4-chamber plane). CONCLUSION: The measurement of the LA-LV angle is a feasible tool to investigate one eventual error of 2D echocardiography.

Orientation of the Atrial Septum to the Inferior Vena Cava May Contribute to the Persistent Patency of the Foramen Ovale.

PURPOSE: There is growing evidence that paradoxical embolism through patent foramen ovale (PFO) is a cause for cryptogenic stroke. However, it is still unclear why the foramen ovale fails to close after birth. We studied whether the 3D relations between the atrial septum (AS) and the inferior vena cava (IVC) are associated with PFO. METHODS: We recruited 30 patients (18-49 years) with a first-ever cryptogenic stroke and 30 age- and sex-matched stroke-free controls. Using cardiac magnetic resonance, an approach to evaluate the 3D relations between the AS and the IVC was developed. The presence of interatrial right-to-left shunt was evaluated with transesophageal echocardiography (TEE) in patients and transcranial Doppler in controls. RESULTS: Of 30 patients, 29 underwent successful TEE, of which 12 (41%) had a shunt. Patients with a shunt had a greater mean 3D angle (γ) between the atrial septal plane and the vector from the orifice of the IVC to the middle of the AS compared with patients without a shunt (45 ± 9° vs. 36 ± 8°, p = 0.017). Of 30 controls, 12 (40%) had a shunt and a greater mean γ compared with controls without a shunt (47 ± 8° vs. 37 ± 10°, p = 0.007). In a pooled analysis, 24 (41%) of 59 subjects with a shunt had a mean γ of 46 ± 9° compared with subjects without a shunt of 37 ± 9° (p < 0.001). CONCLUSIONS: More perpendicular orientation of the atrial septal plane to the orifice of the IVC is associated with PFO, possibly by directing the IVC flow to PFO.

Markers of early vascular aging are not associated with cryptogenic ischemic stroke in the young: A case-control study.

BACKGROUND AND PURPOSE: We aimed to assess the association between covert atherosclerosis, arterial stiffness, and early-onset cryptogenic ischemic stroke (CIS) in a prospective case-control study. METHODS: We enrolled 123 young CIS patients (median age 41 years; 42% women) and 123 age- and sex-matched controls. Carotid intima-media thickness (CIMT), Augmentation Index (AIx), central pulse wave velocity (PWV), and subendocardial viability ratio (SEVR) were compared between patients and controls. Conditional logistic regression was used adjusting for age, systolic blood pressure, diastolic blood pressure, current smoking, total cholesterol/high-density lipoprotein cholesterol (Total-C/HDL-C) ratio, and glycated albumin to assess the independent association between CIMT, arterial stiffness and CIS. RESULTS: Patients with higher CIMT and PWV were older, more often men and they had more frequently well-documented risk factors, lower HDL and higher Total-C/HDL-C ratio compared to other tertiles. In univariate comparisons, we found no differences between patients and controls regarding CIMT, AIx, or PWV. In the entire cohort, patients had a significantly lower SEVR compared to controls (146.3%, interquartile range [IQR] 125.7-170.3 vs. 158.0%, IQR 141.3-181.0, P=0.010). SEVR was lower also in women compared to their controls (132.0%, IQR 119.4-156.1 vs. 158.7%, IQR 142.0-182.8, P=0.001) but no significant difference appeared between male patients and male controls. However, after adjusting for comorbidities and laboratory values these significant differences were lost (odds ratio [OR] 1.52, 95% confidence interval [CI] 0.47-4.91) in the entire cohort and OR 3.89, 95% CI 0.30-50.80 in women). CONCLUSIONS: Higher CIMT and PWV were associated to higher age, male sex, and several well-documented cardiovascular risk factors. However, in this study we could not prove that either covert atherosclerosis or arterial stiffness contribute to pathogenesis of early-onset CIS.

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 (LAVAL-LV) and LA long axis-oriented images (LAVAL-LA) and were compared to 3D segmented LA volume (LAVSAX) 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 LAVAL-LV and 13.4 (10.0-16.9) for LAVAL-LA [mean difference to LAVSAX (95% confidence interval)]. End-diastolic LA long axis 3D deviation angle to LV long axis was 28.3 ± 6.2° [mean ± SD] and LA long axis 3D rotation angle to four-chamber plane 20.5 ± 18.0°. 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. TRIAL REGISTRATION: Main study Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) has been registered previously.

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.

Prolonged ECG with a novel recorder utilizing electrode belt and mobile device in patients with recent embolic stroke of undetermined source: A pilot study.

BACKGROUND: Paroxysmal atrial fibrillation (pAF) is a major risk factor for ischemic stroke, but challenging to detect with routine short-term monitoring methods. In this pilot study, we present a novel method for prolonged ECG and screening for pAF in patients with a recent embolic stroke of unknown source (ESUS). METHODS: Fifteen patients aged ≥ 50 years with a recent ESUS were assigned to wear an external electrode belt-based 1-lead ECG device (Beat2Phone) continuously for 2 weeks (wear time). The device was operated via a mobile phone application in nonhospital conditions. The primary outcome was patient adherence to monitoring. Secondary outcomes were incidence of new pAF, quality-wise comparison to Holter, and usability of the novel ECG monitoring method with Systems Usability Scale (SUS). We also performed a 24- to 48-hr comparison between simultaneous Beat2Phone ECG and a standard Holter in 6 patients. RESULTS: Wear time of Beat2Phone device was over 80% in 5 (33.3%) patients, 50%-80% in 7 (46.6%) patients, and less than 50% in 3 (20%) patients. We detected pAF ≥ 30 s in 1 patient (6.7%). In the simultaneous monitoring with Beat2Phone and Holter, there were a total of 817 (out of 1979) analyzable periods of sinus rhythm or premature atrial or ventricular beats (Cohen's Kappa coefficient 0.92 ± 0.02 between Beat2Phone and Holter), and no pAF events. Beat2Phone ECG showed remarkable SUS scores in user evaluations (average score: 81.4 out of 100 on SUS). CONCLUSIONS: Beat2Phone device was easy to use among ESUS patients and in optimal conditions provided high-quality 1-lead ECG signal for diagnosing pAF. CLINICAL TRIAL REGISTRATION: The study was not registered, as it was a nonrandomized single-arm pilot study.

Use of Statins After Ischemic Stroke in Young Adults and Its Association With Long-Term Outcome.

Background and Purpose- Knowledge of the use of secondary preventive medication in young adults is limited. We studied the use of statins and its association with subsequent vascular events in young adults with ischemic stroke-a patient group with a known low burden of atherosclerosis. Methods- The study population included 935 first-ever 30-day ischemic stroke survivors aged 15 to 49 years from the Helsinki Young Stroke Registry, 1994 to 2007. Follow-up data until 2012 were obtained from the Social Insurance Institution of Finland (Drug Prescription Register), the Finnish Care Register, and Statistics Finland. The association of the use of statins (defined as at least 2 purchases) with all-cause mortality, recurrent stroke, and other recurrent vascular events was assessed through adjusted Cox regression analyses. We further compared propensity score-matched statin users with nonusers. Results- Of our 935 patients, 46.8% used statins at some point during follow-up. Higher age, dyslipidemia, heavy alcohol use, and hypertension were significantly associated with purchasing statins. Statin users exhibited lower risk of all-cause mortality (hazard ratio, 0.38 [95% CI, 0.25-0.58]) and recurrent stroke (hazard ratio, 0.29 [95% CI, 0.19-0.44]) than nonusers, after adjustment for dyslipidemia, stroke subtype, and other confounders. These results remained unchanged after propensity score-matched comparison. Conclusions- Less than half of young ischemic stroke patients used statins; use was affected by age and risk factor profile. Statin use was independently associated with lower risk of all-cause mortality and recurrent stroke.

Continuous 4-week ECG monitoring with adhesive electrodes reveals AF in patients with recent embolic stroke of undetermined source.

BACKGROUND: Atrial fibrillation (AF) frequently escapes routine stroke workup due to its unpredictable and often asymptomatic nature, leaving a significant portion of patients at high risk of recurrent stroke. Recent trials emphasized continuous electrocardiogram (ECG) monitoring in the detection of occult AF. We screened AF in patients meeting the embolic stroke of unknown source (ESUS) criteria using an external miniaturized recorder with an adhesive electrode. METHODS: Patients aged ≥50 with recent ESUS were prospectively screened and assigned to wear a 1-lead ECG device capable to record continuous ECG for up to 4 weeks. Electrodes were replaced every 3-4 days. Primary outcome was proportion of patients completing at least 80% of monitoring. Secondary outcome measures included incidence of AF and initiation of oral anticoagulation therapy after AF detection. RESULTS: Fifty-seven patients were monitored (mean age 64.5 ± 8.2 years, median delay from stroke to the start of monitoring 8 days, IQR 4-44). Of these, 51 patients (89.5%) completed at least 80% of the desired monitoring period. We detected AF ≥30 s in seven patients (12.3%), all of whom initiated anticoagulation therapy. Atrial fibrillation was revealed in six patients (85.7%) within the first week of monitoring. Compared to patients without AF, patients with AF were older (70.6 ± 5.1 vs. 63.6 ± 8.3 years, p < 0.011) and more obese (body mass index 30.0 ± 3.4 vs. 26.6 ± 4.6, p < 0.039). CONCLUSIONS: Prolonged ECG monitoring with an external device using adhesive electrodes is feasible in ESUS patients, since nine out of ten patients used the device appropriately and AF was detected in one out of eight patients.

Time has not passed for the tilt table test.

INTRODUCTION: The tilt table test is used for determining the loss of consciousness, and in the case of reflex syncope, for gaining insight into the circulatory mechanism. In 2015, all tilt tests within the Hospital District of Helsinki and Uusimaa (HUS) were performed in the clinical physiology unit of the HUS Medical Imaging Center at Peijas Hospital. METHODS: The patients' medical history, circulation monitor printouts, and medical reports were recorded from all tilt tests carried out during 2015. Positive tilt tests were classified according to the VASIS classification and the elapsed time to loss of consciousness was observed. RESULTS: Among a total of 133 patients, abnormal upright tolerance was found in 30 per cent of the patients. The average time to loss of consciousness was 35.2 minutes. The most common mechanism of syncope was mixed reaction (60.0%), whereas vasovagal reaction (22.5%), cardioinhibitory reaction (10.0%), and lacking stroke volume response (7.5%) were less common. CONCLUSIONS: Practices of referral for the tilt table test vary among the different units of HUS. In our material, the cardioinhibitory reaction was less common than in previous studies.

Acute-Phase Blood Pressure Levels Correlate With a High Risk of Recurrent Strokes in Young-Onset Ischemic Stroke.

BACKGROUND AND PURPOSE: High blood pressure (BP) in acute stroke has been associated with a poor outcome; however, this has not been evaluated in young adults. METHODS: The relationship between BP and long-term outcome was assessed in 1004 consecutive young, first-ever ischemic stroke patients aged 15 to 49 years enrolled in the Helsinki Young Stroke Registry. BP parameters included systolic (SBP) and diastolic BP, pulse pressure, and mean arterial pressure at admission and 24 hours. The primary outcome measure was recurrent stroke in the long-term follow-up. Adjusted for demographics and preexisting comorbidities, Cox regression models were used to assess independent BP parameters associated with outcome. RESULTS: Of our patients (63% male), 393 patients (39%) had prestroke hypertension and 358 (36%) used antihypertensive treatment. The median follow-up period was 8.9 years (interquartile range 5.7-13.2). Patients with a recurrent stroke (n=142, 14%) had significantly higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure (P<0.001) and 24-h SBP, diastolic BP, and mean arterial pressure compared with patients without the recurrent stroke. Patients with SBP ≥160 mm Hg compared with those with SBP <160 mm Hg had significantly more recurrent strokes (hazard ratio 3.3 [95% confidence interval, 2.05-4.55]; P<0.001) occurring earlier (13.9 years [13.0-14.6] versus 16.2 [15.8-16.6]; P<0.001) within the follow-up period. In multivariable analyses, higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure were independently associated with the risk of recurrent stroke, while the 24-hour BP levels were not. CONCLUSIONS: In young ischemic stroke patients, high acute phase BP levels are independently associated with a high risk of recurrent strokes.

24-hour ambulatory blood pressure and cryptogenic ischemic stroke in young adults.

BACKGROUND: In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls. PATIENTS AND METHODS: In this substudy of the international multicenter case-control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18-49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status. RESULTS: 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20-12.42), in participants without antihypertensives (4.86; 1.07-22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47-36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37-17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged. CONCLUSIONS: Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

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.

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

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.

Endothelial Dysfunction is Associated With Early-Onset Cryptogenic Ischemic Stroke in Men and With Increasing Age.

Background The aim of this study was to assess the association between endothelial function and early-onset cryptogenic ischemic stroke (CIS), with subgroup analyses stratified by sex and age groups. Methods and Results We prospectively enrolled 136 consecutive patients aged 18 to 49 years (median age, 41 years; 44% women) with a recent CIS and 136 age- and sex-matched (±5 years) stroke-free controls. Endothelial function was measured with an EndoPAT 2000 device and analyzed as tertiles of natural logarithm of reactive hyperemia index with lower values reflecting dysfunction. We used conditional logistic regression adjusting for age, education, hypertension, diabetes mellitus, dyslipidemia, current smoking, heavy drinking, obesity, and diet score to assess the independent association between endothelial function and CIS. Patients in the lowest tertile of natural logarithm of reactive hyperemia index were more often men and they more frequently had a history of dyslipidemia; they were also more often obese, had a lower diet score, and lower high-density lipoprotein cholesterol. In the entire cohort, we found no association in patients with endothelial function and CIS compared with stroke-free controls. In sex- and age-specific analyses, endothelial dysfunction was associated with CIS in men (adjusted odds ratio [OR], 3.50 for lowest versus highest natural logarithm of reactive hyperemia index tertile; 95% CI, 1.22-10.07) and in patients ≥41 years (OR, 5.78; 95% CI, 1.52-21.95). These associations remained significant when dyslipidemia was replaced with the ratio of total to high-density lipoprotein cholesterol. Conclusions Endothelial dysfunction appears to be an independent player in early-onset CIS in men and patients approaching middle age.

Left Atrial Dynamics Is Altered in Young Adults With Cryptogenic Ischemic Stroke: A Case-Control Study Utilizing Advanced Echocardiography.

Background Ischemic stroke in young individuals often remains cryptogenic. Some of these strokes likely originate from the heart, and atrial fibrosis might be one of the etiological mechanisms. In this pilot study, we investigated whether advanced echocardiography findings of the left atrium (LA) of young cryptogenic stroke patients differ from those of stroke-free controls. Methods and Results We recruited 30 cryptogenic ischemic stroke patients aged 18 to 49 years and 30 age- and sex-matched stroke-free controls among participants of the SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study (NCT01934725). We measured basic left ventricular parameters and detailed measures of the LA, including 4-dimensional volumetry, speckle tracking epsilon, strain rate, and LA appendix orifice variation. Data were compared as continuous parameters and by tertiles. Compared with controls, stroke patients had smaller LA reservoir volumes (10.2 [interquartile range, 5.4] versus 13.2 [5.4] mL; P=0.030) and smaller positive epsilon values (17.8 [8.5] versus 20.8 [10.1]; P=0.023). In the tertile analysis, stroke patients had significantly lower left atrial appendage orifice variation (3.88 [0.75] versus 4.35 [0.90] mm; P=0.043), lower LA cyclic volume change (9.2 [2.8] versus 12.8 [3.5] mL; P=0.023), and lower LA contraction peak strain rate (-1.8 [0.6] versus -2.3 [0.6]; P=0.021). We found no statistically significant differences in left ventricular measures. Conclusions This preliminary comparison suggests altered LA dynamics in young patients with cryptogenic ischemic stroke, and thus that LA wall pathology might contribute to these strokes. Our results await confirmation in a larger sample.

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/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.

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.

Use of antihypertensive medication after ischemic stroke in young adults and its association with long-term outcome.

BACKGROUND: Knowledge on the use of secondary preventive medication in young adults is limited. METHODS: We included 936 first-ever ischemic stroke 30-day survivors aged 15-49, enrolled in the Helsinki Young Stroke Registry, 1994-2007. Follow-up data until 2012 came from Finnish Care Register, Statistics Finland, and Social Insurance Institution of Finland. Usage thresholds were defined as non-users, low (prescription coverage <30%), intermediate (30-80%) and high users (>80%). Adjusted Cox regression allowed assessing the association of usage with all-cause mortality and recurrent vascular events. RESULTS: Of our patients, 40.5% were non-users, 7.8% had low usage, 11.8% intermediate usage and 40.0% high usage. Median follow-up was 8.3 years. Compared to non-users, risk of mortality and recurrent stroke or TIA was lower for patients with low-intermediate (HR 0.40, 95% CI 0.22-0.65; HR 0.31, 95% CI 0.18-0.53) and high usage (HR 0.25, 95% CI 0.15-0.42; HR 0.30, 95% CI 0.19-0.46), after adjustment for confounders. CONCLUSIONS: Use of antihypertensives was suboptimal in one-third of patients in whom antihypertensives were initially prescribed. Users were at lower risk of mortality and recurrent stroke or TIA compared to non-users. Key Messages The use of antihypertensive medication is suboptimal in one-third of patients in whom antihypertensive medication was initially prescribed after ischemic stroke at young age. The risk of mortality and recurrent stroke or TIA is lower for users of antihypertensive medication after ischemic stroke at young age compared to non-users, after adjustment for relevant confounders including pre-existing hypertension and prior use of antihypertensive medication. Specific guidelines on antihypertensive medication use after ischemic stroke at young age are lacking. However, our results may motivate doctors and patients in gaining better usage of antihypertensive medication, since better usage was associated with more favorable outcome in this study.

Twelve-lead electrocardiogram and mortality in young adults after ischaemic stroke.

INTRODUCTION: Ischaemic stroke at young age carries an increased risk for mortality in comparison to the general population, but factors associated with mortality have been poorly studied. We studied the role of electrocardiogram in mortality risk stratification in young stroke patients. PATIENTS AND METHODS: The Helsinki Young Stroke Registry encompasses 1008 patients aged <50 years with ischaemic stroke. We included 690 patients for this electrocardiogram substudy. Our endpoints were all-cause and cardiovascular mortality. Cox regression models - adjusted for clinical and demographic characteristics - were used to identify the electrocardiogram parameters associated with these endpoints. RESULTS: At a mean follow-up of 8.8 years, cumulative all-cause and cardiovascular mortality were 16.1 and 9.1%, respectively. Factors associated with both endpoints included diabetes (type 1 for all-cause, type 2 for cardiovascular mortality), heavy drinking, malignancy, as well as stroke severity and aetiology. Of the electrocardiogram parameters, higher heart rate (hazard ratio 1.35 per 10/min, 95% confidence interval 1.21-1.49), a shorter P-wave (hazard ratio 0.78 per 10 ms decrement, 0.64-0.92) and longer QTc interval (1.09 per 10 ms, 1.03-1.16) were associated with increased all-cause mortality. Only a higher heart rate (1.42 per 10/min, 1.24-1.60) was associated with death from cardiovascular causes. CONCLUSIONS: A higher heart rate during the subacute phase after stroke is associated with an elevated risk of all-cause and cardiovascular mortality in young adults. A longer QTc interval is associated only with higher all-cause mortality. P-wave characteristics and their possible association with mortality need further studies.

ECG markers associated with ischemic stroke at young age - a case-control study.

INTRODUCTION: Certain electrocardiographic (ECG) abnormalities are associated with ischemic stroke (IS), especially cardioembolic subtype. Besides atrial fibrillation, markers of left ventricular hypertrophy (LVH) or atrial pathology also reflect elevated risk. We studied the association of ECG markers with IS in young adults. METHODS: We performed a case-control study including 567 consecutive IS patients aged 15-49 years (inclusion period: 1994-2007) and one or two age- and sex-matched control subjects enrolled during 1978-1980 (n = 1033), and investigated also the stroke aetiologic subgroups. We studied ECGs of all participants for markers of atrial abnormality, i.e. P-terminal force (PTF) on lead V1, interatrial blocks (IAB; P-wave duration ≥110 ms), and LVH. Conditional logistic regression analyses were used. RESULTS: IAB (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.16-2.13) and PTF combined with LVH (HR: 6.83, 95% CI: 1.65-28.31), were independently associated with IS. LVH, abnormal P-wave (HR: 6.87, 95% CI: 1.97-135.29), PTF, IAB, and combinations of these P-wave abnormalities with LVH - were associated with cardioembolic subtype. Abnormal P-wave and IAB were associated with cryptogenic stroke subtype. In unadjusted analysis, LVH was associated with small-vessel disease subtype. CONCLUSION: P-wave abnormalities on ECG were associated with cardioembolic but also with a cryptogenic subtype of IS. Key messages ECG patterns associated with atrial pathology are markers of increased risk of ischemic stroke in young adults. The ECG markers reflecting atrial pathology were seen in patients with cardioembolic and cryptogenic subtypes of ischemic stroke.