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Many algorithms have been developed to ensure the safety and accuracy of cardiac implantable electric devices (CIED). A specific algorithm designed to prevent pacemaker induced tachycardia (PMT) after a premature ventricular complex (PVC response) is available in all Abbott (former St. Jude Medical) CIED. However, a few case reports suggest that this algorithm may be proarrhythmic when programmed to Atrial Pace (A-Pace on PVC).We analyzed the data of all (n = 333) Abbot implantable cardioverter defibrillator (ICD) and cardiac resynchronization defibrillator (CRT-D) devices followed remote using the Merlin.net Patient Care Network in our institute in 2020. Status of the PVC response algorithm A-Pace on PVC or Off was collected, and all atrial mode switch (AMS) episodes longer than 30 s were thoroughly evaluated. Data on clinical characteristics of the patients was collect from the electronic patient records.A total of 173 patients had A-Pace on PVC and twenty-five of them (14%) had at least one atrial high rate episode (AHRE)30 s (AHRE) triggered by the action of this algorithm. The median PVC count was higher in patients who had algorithm triggered AHRE than in those with no algorithm-triggered AHRE (1.7% [IQR 0-3.2] vs. 0% [IQR 0-1.1], p .0001). The major clinical characteristics were comparable in the two groups.The A-Pace on PVC setting was frequently used in our patients. Our study shows that a considerable number of patients had at least one AHRE triggered by the algorithm. The use of this algorithm should be carefully reconsidered.

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.

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

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.

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.

Funding Acknowledgements Type of funding sources: None. Introduction Up to 50% of ischemic strokes in adults aged between 18 and 50 are cryptogenic by nature. Heart has been a hypothesised source. Purpose: Purpose of the study was to investigate the wash in and wash out of gadolinium based contrast agent in the left atrial appendage, and cardiac chambers in first pass cardiac magnetic resonance imaging. Methods The study comprised 30 patients with first-ever cryptogenic ischemic stroke and 30 age and gender matched stroke-free controls included in the prospective multicenter study Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers and Outcome (SECRETO; NCT01934725). Cardiac magnetic resonance imaging was performed on all participants with a 1.5T magnetic resonance system. Dynamic contrast enhanced T1 weighted first pass perfusion images were acquired in the superior vena cava, the left atrial appendage (Fig. 1), and the left ventricle. The images were analyzed for time-intensity curves (Fig. 2), and results were normalised to individual heart rate. Arrival times, peak times, areas under the curves, relative blood flows (defined as area under the curve/full width at half maximum), and maximum and minimum rates of bolus wash in / wash out were calculated. Results The wash in of the contrast agent bolus was similar in patients and controls. Arrival times and peak timings showed similar characteristics in patients and controls in the left atrial appendage (arrival time: 12.4 [2.3] vs. 13.5 [3.6] cardiac cycles, p = 0.657; peak time: 19.6 [5.1] vs. 19.8 [6.9] cardiac cycles, p = 0.929) and the left atrium (arrival time: 12.2 [2.8] vs. 13.0 [3.6] cardiac cycles, p = 0.535; peak time: 18.7 [5.5] vs. 18.1 [5.2] cardiac cycles, p = 0.790). Areas under under the curves and relative blood flows were similar in patients and controls. A significant difference between patients and controls was found in the wash out rate of gadolinium in the left ventricle (-28 [11] vs. -36 [13] 1/cardiac cycles, p = 0.012), indicating slightly slower wash out in the patients. Conclusions Cryptogenic ischemic stroke in the young is not associated with prolonged blood flow in the left atrial appendage or left atrium. There were no significant differences in the first pass perfusion between subjects and healthy controls. However, there might be a slight tendency for stagnation of blood flow in the left ventricles of cryptogenic stroke patients.

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/).

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.

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.

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.

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.

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.

normal LVEF, NT-proBNP values before CV were above the reference normal values ( 280 pg/ml) in all but one patient. Nine patients (33%) had an early atrial fibrillation recurrence (within 3 weeks). Persistence of sinus rhythm was associated with a significant reduction in NT-proBNP values (from 672 280 to 337 230 pg/ml; p 0.001). No significant differences were instead observed in the subjects with an early recurrence . No correlation was found between NT-proBNP values and, respectively, duration of AF, ejection fraction, left atrial diameter and HRV parameters. A strong correlation was found instead with left appendage emptying velocity (r -0.73; p 0.001). Conclusions: These data indicate that in patients with persistent AF, abnormal atrial dynamics are strongly associated with NT-proBNP levels. Recovery of sinus rhythm is accompanied by a rapid reduction of NTproBNP values likely to be due to the restoration of a more physiological hemodynamic function in the atria.