Project no. NVKP 16-1&#8211;2016-0017 (&#8217;National Heart Program&#8217;) has been implemented with the support provided by the National Research, Development, and Innovation Fund of Hungary, financed under the NVKP 16 funding scheme. The research was financed by the Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development and Bioimaging thematic programs of the Semmelweis University.&#160;

In the following part we describe the protocol steps of clinical and imaging evaluation of atrial communications before transcatheter closure based on international clinical guidelines. These protocols follow the guidelines of the Semmelweis University Regional and Institutional Committee of Science and Research Ethics. Informed written patient consent is needed.
1. Clinical evaluation and workflow of cryptogen stroke and PFO for transcatheter closure
<ol>
	<li>For the diagnostic work-up of stroke, determine whether the stroke is ischemic or hemorrhagic in origin using computed tomography scan (CT) or magnetic resonance brain imaging (MRI).&#160;</li>
	<li>In case of ischemic etiology, perform subsequent CT- or MR-angiography of the head and neck to exclude any intracranial- and cerebral- or extracerebral vascular pathology, which would warrant specific therapy.&#160;</li>
	<li>Perform blood work to test for a hypercoagulable state, most importantly an antiphospholipid syndrome or other genetic alterations leading to a coagulation disorder.&#160;A patient with hypercoagulability is not a good candidate for closure, as thrombus formation could occur on the surface or near the implanted device in these cases4,5.</li>
	<li>Use inpatient ECG monitoring to rule out atrial fibrillation. 
	NOTE: Further extended outpatient rhythm monitoring with an ambulatory 24-36-hour Holter, with an external event recorder or even with an insertable monitoring device, should be considered to detect the occurrence of atrial fibrillation, which is silent in a considerable proportion of stroke patients.</li>
	<li>Perform a TTE scan to exclude cardioembolic sources other than atrial fibrillation, such as non-compaction cardiomyopathy, dilated cardiomyopathy with severely depressed left ventricular ejection fraction, any intracardiac mass, vegetation or intracavitary thrombus and to assess the morphology of the interatrial septum for the presence of septal aneurysm. 
	NOTE: The latter can raise the suspicion for the presence of PFO.</li>
	<li>For the final work-up step in patient selection for PFO closure, make a multidisciplinary team decision involving the neurologist, the cardiologist and the cerebral imaging specialist.</li>
</ol>
2. Clinical evaluation and workflow of ASD for transcatheter closure
<ol>
	<li>Perform preprocedural cardiac MR (CMR) and right heart catheterisation (RHC) to diagnose complex congenital heart disease, where an ASD is only one element of a complex case. In these cases, closure of the ASD is usually part of a complex surgical repair procedure, rather than a transcatheter one.&#160; 
	NOTE: Simple, secundum type ASDs with a volume-overloaded RV due to a pulmonary/systemic flow (Qp/Qs) ratio of &#62;1.5 and not elevated RV pressure are suitable for a single-step transcatheter closure if surrounded by a minimum rim of 5 mm6. Multi-fenestrated defects are often amenable for closure with multiple devices.&#160;</li>
	<li>Measure pulmonary vascular resistance (PVR) at baseline by RHC when shunting is excessive and there is elevated RV systolic pressure.
	<ol>
		<li>In case of moderately elevated PVR (4-8 Wood units), perform a staged transcatheter closure by implanting a fenestrated closure device first to reduce the amount of initial shunting. Perform full closure after improvement of RV function and a decrease in PVR a couple of months later in a second step. Markedly elevated baseline PVR values above 8 Wood units usually form a contraindication for closure, as this would deteriorate RV function even further.</li>
	</ol>
	</li>
</ol>
3. 2D transthoracic echocardiography imaging for the interatrial septum
NOTE: The assessment of interatrial septum is recommended according to the 2015 ASE guidelines2. The patient is lying in the left decubitus position with the left arm placed under the head. Standard parasternal, apical and subcostal views are obtained.
<ol>
	<li>Use the subxiphoid frontal four-chamber view; it provides good axial resolution to measure the diameter of the defect along its long axis.&#160;</li>
	<li>Use the subxiphoid sagittal view to visualize the atrial septum along its superior&#8211;inferior axis.</li>
	<li>Use the apical four-chamber view to estimate haemodinamic consequencies of interatrial left to right shunting including RA, RV dilation and RV pressure.</li>
	<li>Use the parasternal short-axis view to measure the aortic and posterior rim of the septal defect.</li>
</ol>
4. 2D/3D Transthoracic Echocardiography Imaging for the anatomical and functional quantification of heart chambers
NOTE: Assessment of atria is recommended according to the consensus statement from the ASE and EACVI on chamber quantification7.
<ol>
	<li>Perform conventional volumetric and functional LA measurement.</li>
	<li>Perform advanced echocardiography techniques using speckle tracking. Optimize acquisition frame rates for speckle tracking to provide the highest frame rate per cardiac cycle without significantly decreasing spatial resolution.
	<ol>
		<li>In the 2D LA strain curve, set the zero strain reference at the left ventricular end-diastole. Calculate the LA strain values of each phase as the difference of two of these measurements8. LA function is divided into reservoir, conduit and contraction phase.&#160;All considerations made for LA measurements can be applied for RA assessment as well.</li>
	</ol>
	</li>
	<li>Measure the tricuspid annular plane systolic excursion, the RV fractional area change, the Doppler tissue imaging (DTI) S&#8217; velocity, and the RV ejection fraction from 3D volumetric evaluation. Perform 2D speckle tracking analysis with RV strain parameters for the evaluation of RV systolic function9.&#160; 
	NOTE: RV measurements are highly important in case of hemodynamically significant ASD, when RV function can be impaired and significant pulmonary hypertension can occur.</li>
	<li>Obtain electrocardiographically gated full-volume 3D data sets from apical four chamber view for 3D LA, LV and RV volume and function measurement, representing parameters of incremental prognostic value over 2D LA parameters10,11.</li>
	<li>Perform conventional volumetric and functional LV measurements, including LV diastolic function assessment using mitral inflow and annular tissue Doppler imaging. 
	NOTE: In case of diastolic dysfunction, acute heart failure may develope after ASD closure due to LV volume overload.</li>
	<li>Assess LV global longitudinal strain due to its prognostic value. 
	NOTE: However, circumferential and radial strain can be also assessed12,13.</li>
</ol>
5. Transesophageal echocardiography imaging for the interatrial septum
<ol>
	<li>Perform TEE examination in patients clinically suitable for potential percutaneous device closure to assess technical feasibility of the closure as well. Otherwise, perform TTE examination or transcranial doppler (TCD) using agitated saline to prove the presence of an interatrial shunt2,14,15,16. Informed written patient consent is mandatory before TEE examination.</li>
	<li>Position the patient on the left lateralis decubitus in case of preoperative screening TEE and on the back position in case of intraoperative TEE. Ensure that patients fast for at least 4 h and remove dental fixtures.</li>
	<li>Use topical oropharyngeal anesthesia (such as lidocaine) and intravenous sedatives (such as midazolam, typical dose 1-5mg) before screening TEE. The intraoperative guiding TEE is performed usually under general anaesthesia.</li>
	<li>Monitor ECG, blood pressure and oxygen saturation. Furthermore, availability and experience with resuscitation equipment is mandatory.</li>
	<li>Define the number, size and location of defects as well as the surrounding atrial septal tissue (rims) and the presence of atrial septal aneurysm. Determine the hemodynamic consequences of atrial septal defects using conventional 2D TEE views, of which midesophageal bicaval and aortic valve short axis view are the most important (Figure 2).</li>
	<li>Verify communication through the foramen using agitated saline contrast during the Valsalva maneuver, when the right atrial pressure temporarily increases, the overlapping septum primum and secundum opens, and the bubbles can cross the canal of PFO from the right atria to the left atria within 3 cardiac cycles. 
	NOTE: The amount of crossing bubbles depends on the size of PFO. A large (grade III) shunt is defined when the number of bubbles exceeds 20.</li>
	<li>Use 3D TEE acquisition methods mainly from the midesophageal short axis view or the bicaval view. Use the narrow-angled (zoomed) and wide-angled (full volume) mode to obtain additional information on the complex and dynamic anatomy of interatrial septum. Measure the size of atrial septal defect at the atrial end-diastole and end-systole in en face views from either the RA or LA (Figure 3).</li>
	<li>Use intraoperative transesophageal echocardiography to guide all steps of the procedure mainly from midesophageal bicaval and short axis view, including advancing the guidewire through the PFO tunnel or ASD and closure device delivery (Figure 1, Figure 4, Figure 5).</li>
	<li>Perform balloon sizing of the stretched diameter of ASD using fluoroscopy and TEE as well. 
	NOTE: The maximum size of the closure device is 90% of the atrial septal length; nevertheless, the ratio of the device to defect should not exceed 2:1 (Figure 6).</li>
	<li>Before the delivery system detachment, evaluate the presence of the residual shunt evaluation and measure the atrial septal tissue rim and atrial roof to closure device distance using a four chamber, short axis and bicaval TEE view.</li>
</ol>
6. Postoperative follow-up
<ol>
	<li>Perform the TTE study before hospital discharge and repeat within 1 month to assess device position, residual shunt and pericardial effusion due to device errosion.</li>
	<li>Perform TTE examination and 12-lead electrocardiography follow up studies at 6, and 12 months, with a subsequent evaluation every year.
	<ol>
		<li>Measure conventional Doppler parameters to evaluate the effect of transcatheter ASD closure on left-sided chambers.</li>
		<li>Measure atrial and ventricular volumetric changes and longitudinal strain parameters are measured in order to track cardiac remodelling (Figure 7, Figure 8). Atrial arrhythmias occur mainly within 1 month after device deployment17.</li>
	</ol>
	</li>
</ol>

<ol>
	<li>Meier, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Percutaneous+closure+of+patent+foramen+ovale+in+cryptogenic+embolism.">Percutaneous closure of patent foramen ovale in cryptogenic embolism.</a> New England Journal of Medicine. 368 (12), 1083-1091 (2013).</li><li>Silvestry, F. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=et+al.Guidelines+for+the+Echocardiographic+Assessment+of+Atrial+Septal+Defect+and+Patent+Foramen+Ovale:+From+the+American+Society+of+Echocardiography+and+Society+for+Cardiac+Angiography+and+Interventions.">et al.Guidelines for the Echocardiographic Assessment of Atrial Septal Defect and Patent Foramen Ovale: From the American Society of Echocardiography and Society for Cardiac Angiography and Interventions.</a> Journal of the American Society of Echocardiography. 28 (8), 910-958 (2015).</li><li>Saric, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+the+Use+of+Echocardiography+in+the+Evaluation+of+a+Cardiac+Source+of+Embolism.">Guidelines for the Use of Echocardiography in the Evaluation of a Cardiac Source of Embolism.</a> Journal of the American Society of Echocardiography. 29 (1), 1-42 (2016).</li><li>Krumsdorf, U., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incidence+and+clinical+course+of+thrombus+formation+on+atrial+septal+defect+and+patient+foramen+ovale+closure+devices+in+1,000+consecutive+patients.">Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in 1,000 consecutive patients.</a> Journal of the American College of Cardiology. 43 (2), 302-309 (2004).</li><li>Canpolat, U., G&#252;rses, K. M., Sunman, H., Kaya, E. B., Aytemir, K., Oto, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Embolic+stroke+due+to+left+atrial+thrombus+2+years+after+PFO+closure.">Embolic stroke due to left atrial thrombus 2 years after PFO closure.</a> Herz. 39 (1), 161-162 (2014).</li><li>Butera, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+isolated+secundum+atrial+septal+defects:+impact+of+age+and+defect+morphology+in+1,013+consecutive+patients.">Treatment of isolated secundum atrial septal defects: impact of age and defect morphology in 1,013 consecutive patients.</a> American Heart Journal. 156 (4), 706-712 (2008).</li><li>Badano, L. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardization+of+left+atrial,+right+ventricular,+and+right+atrial+deformation+imaging+using+two-dimensional+speckle+tracking+echocardiography:+a+consensus+document+of+the+EACVI/ASE/Industry+Task+Force+to+standardize+deformation+imaging.">Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: a consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging.</a> European Heart Journal of Cardiovascular Imaging. 19 (6), 591-600 (2018).</li><li>Hayashi, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimal+Analysis+of+Left+Atrial+Strain+by+Speckle+Tracking+Echocardiography:+P-wave+versus+R-wave+Trigger.">Optimal Analysis of Left Atrial Strain by Speckle Tracking Echocardiography: P-wave versus R-wave Trigger.</a> Echocardiography. 32 (8), 1241-1249 (2015).</li><li>Rudski, L. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+the+echocardiographic+assessment+of+the+right+heart+in+adults:+a+report+from+the+American+Society+of+Echocardiography+endorsed+by+the+European+Association+of+Echocardiography,+a+registered+branch+of+the+European+Society+of+Cardiology,+and+the+Canadian+Society+of+Echocardiography.">Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography.</a> Journal of the American Society of Echocardiography. 23 (7), 685-713 (2010).</li><li>Wu, V. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prognostic+value+of+LA+volumes+assessed+by+transthoracic+3D+echocardiography:+comparison+with+2D+echocardiography.">Prognostic value of LA volumes assessed by transthoracic 3D echocardiography: comparison with 2D echocardiography.</a> Journal of the American College of Cardiology: Cardiovascular Imaging. 6 (10), 1025-1035 (2013).</li><li>Badano, L. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Left+Atrial+Volumes+and+Function+by+Three-Dimensional+Echocardiography:+Reference+Values,+Accuracy,+Reproducibility,+and+Comparison+With+Two-Dimensional+Echocardiographic+Measurements.">Left Atrial Volumes and Function by Three-Dimensional Echocardiography: Reference Values, Accuracy, Reproducibility, and Comparison With Two-Dimensional Echocardiographic Measurements.</a> Circulation: Cardiovascular Imaging. 9 (7), (2016).</li><li>Edvardsen, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+year+2015-16+in+the+European+Heart+Journal-Cardiovascular+Imaging.+Part+II.">The year 2015-16 in the European Heart Journal-Cardiovascular Imaging. Part II.</a> European Heart Journal: Cardiovascular Imaging. 18 (12), 1322-1330 (2017).</li><li>Galderisi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardization+of+adult+transthoracic+echocardiography+reporting+in+agreement+with+recent+chamber+quantification,+diastolic+function,+and+heart+valve+disease+recommendations:+an+expert+consensus+document+of+the+European+Association+of+Cardiovascular+Imaging.">Standardization of adult transthoracic echocardiography reporting in agreement with recent chamber quantification, diastolic function, and heart valve disease recommendations: an expert consensus document of the European Association of Cardiovascular Imaging.</a> Europen Heart Journal: Cardiovascular Imaging. 18 (12), 1301-1310 (2017).</li><li>Marriott, K., Manins, V., Forshaw, A., Wright, J., Pascoe, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detection+of+right-to-left+atrial+communication+using+agitated+saline+contrast+imaging:+experience+with+1162+patients+and+recommendations+for+echocardiography.">Detection of right-to-left atrial communication using agitated saline contrast imaging: experience with 1162 patients and recommendations for echocardiography.</a> Journal of the American Society of Echocardiography. 26 (1), 96-102 (2013).</li><li>Mojadidi, M. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=et+al+Accuracy+of+conventional+transthoracic+echocardiography+for+the+diagnosis+of+intracardiac+right-to-left+shunt:+a+meta-analysis+of+prospective+studies.">et al Accuracy of conventional transthoracic echocardiography for the diagnosis of intracardiac right-to-left shunt: a meta-analysis of prospective studies.</a> Echocardiography. 31 (9), 1036-1048 (2014).</li><li>Mojadidi, M. K., Bogush, N., Caceres, J. D., Msaouel, P., Tobis, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+accuracy+of+transesophageal+echocardiogram+for+the+detection+of+patent+foramen+ovale:+a+meta-analysis.">Diagnostic accuracy of transesophageal echocardiogram for the detection of patent foramen ovale: a meta-analysis.</a> Echocardiography. 31 (6), 752-758 (2014).</li><li>Staubach, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+onset+atrial+fibrillation+after+patent+foramen+ovale+closure.">New onset atrial fibrillation after patent foramen ovale closure.</a> Catheter and Cardiovascular Interventions. 74 (6), 889-895 (2009).</li><li>Singh, H. S., Katchi, F., Naidu, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PFO+Closure+for+Cryptogenic+Stroke:+A+Review+and+Clinical+Treatment+Algorithm.">PFO Closure for Cryptogenic Stroke: A Review and Clinical Treatment Algorithm.</a> Cardiology in Review. 25 (4), 147-157 (2017).</li><li>Sanna, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cryptogenic+stroke+and+underlying+atrial+fibrillation.">Cryptogenic stroke and underlying atrial fibrillation.</a> New England Journal of Medicine. 370 (26), 2478-2486 (2014).</li><li>Prefasi, D., Mart&#237;nez-S&#225;nchez, P., Fuentes, B., D&#237;ez-Tejedor, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+utility+of+the+RoPE+score+in+cryptogenic+stroke+patients+&#8804;50+years+in+predicting+a+stroke-related+patent+foramen+ovale.">The utility of the RoPE score in cryptogenic stroke patients &#8804;50 years in predicting a stroke-related patent foramen ovale.</a> International Journal of Stroke. 11 (1), 7-8 (2016).</li><li>Yamano, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=et+al+Appropriate+selection+of+echocardiographic+guidance+for+transcatheter+atrial+septal+defect+closure.">et al Appropriate selection of echocardiographic guidance for transcatheter atrial septal defect closure.</a> International Journal of Cardiovascular Imaging. 36 (5), 855-863 (2020).</li><li>Oto, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transthoracic+echocardiography+guidance+during+percutaneous+closure+of+patent+foramen+ovale.">Transthoracic echocardiography guidance during percutaneous closure of patent foramen ovale.</a> Echocardiography. 28 (10), 1074-1080 (2011).</li></ol>

Authors declare no conflict of interest.&#160;

Careful patient selection for transcatheter PFO closure represents one of the most challanging steps of the clinical evaluation, as ruling out atrial fibrillation can be difficult. Several trials in the past few years have suggested greater yield with longer term monitoring to detect atrial fibrillation.18 The Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL-AF) trial detected increased atrial fibrillation rate in the insertable cardiac monitor group (8,9%) compared with standard mon...

Patent Foramen Ovale (PFO) is not a true tissue deficiency of atrial septum; it is present in about 20-25% of&#160;the adult population, and in most cases it does not have any clinical significance (Figure 1). Cryptogenic stroke accounts for ~30% of ischemic strokes and is defined as a&#160;condition without an apparent cause at the early inpatient work-up. Patients under 45 years of age represent 10% of stroke burden with as much as 40% defined as cryptogenic. Secondary prevention of stroke using transcatheter closure technique remains paramount in reducing morbidity and mortality1.
Atrial septal defects (ASDs) include different lesions on different atrial septum locations, resulting in shunting. The most common form is ostium secundum ASD, usually optimal for percutan devise closure. ASDs are generally discovered during the workup of right ventricular (RV) dysfunction and/or dilatation, and rarely after a suspected paradoxical embolism or cryptogenic stroke2,3.
Transthoracic (TTE) and transesophageal (TEE) echocardiography is performed for qualitative and quantitative assessment of atrial septum deficiencies. Three dimensional (3D) TEE provides more in depth information of the interatrial septum, and it gives more precise imaging of catheters and the closure device during intraoperative guiding. Postoperative follow up evaluations with TTE should be performed at 1, 6, and 12 months after the procedure, with a subsequent evaluation every year to assess device position, residual shunts, pericardial effusion, changes in size and function of the cardiac chambers and pulmonary circulation. Further advanced echocardiography techniques using speckle tracking echocardiography may help to understand potential functional left atrial remodeling following percutaneous closure and its impact on atrial arrhythmias2.

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		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:219px;">TomTec Imaging workstation</td>
			<td style="width:242px;">TomTec Imaging, Unterschleissheim, Germany</td>
			<td style="width:151px;"></td>
			<td style="width:206px;">4D LALV Function analysing software</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:219px;">Ultrasound machine</td>
			<td style="width:242px;">Philips Epiq CvX</td>
			<td style="width:151px;">serial number US81881251</td>
			<td style="width:206px;">X5-1 and X7 transducers</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:219px;">Wiwe external ECG single chanel recorder</td>
			<td style="width:242px;">Sanat Metal</td>
			<td style="width:151px;">5-810-200-1611</td>
			<td style="width:206px;">external ECG single chanel recorder</td>
		</tr>
	</tbody>
</table>

echocardiographic evaluation of atrial communications before transcatheter closure

Transthoracic (TTE) and transesophageal echocardiography (TEE) is the standard imaging method for atrial septal defect (ASD) and patent foramen ovale (PFO) detection, for patient selection for transcatheter ASD/PFO closure,&#160;for intraoperative guidance and for long-term follow-up. The size, shape, location and the number of the atrial communications schould be determined. The accuracy of PFO detection can be improved by using agitated saline together with maneuvers to transiently increase the right atrial (RA) pressure. The appearance of microbubbles in the left atrium (LA) within 3 cardiac cycles after opacification of the RA is considered positive for the presence of an intracardiac shunt. Three dimensional TEE identifies further septal fenestrations and describes the dynamic morphology of ASD/PFO and atrial septal aneurysm. Follow-up evaluations with TTE is recommended at 1, 6, and 12 months after the procedure, with a subsequent evaluation every year. Previous studies showed an increased incidence of atrial arrhythmias early after device closure. Speckle tracking analysis may help to understand functional left atrial remodeling following percutaneous closure and its impact on atrial arrhythmias.

Clinical evaluation of symptomatic, 41 years old female patient revealed ostium secundum type ASD and floppy atrial septum using TTE and TEE examination 
TTE examination showed right ventricular and biatrial enlargement with elevated pulmonary artery systolic pressure. TEE examination was used to estimate the size and shape of ASD using 2D and 3D methods. 2D, 3D native and balloon sizing TEE measurements were compared (Figure 4, Figure 5, <...

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Echocardiographic Evaluation of Atrial Communications before Transcatheter Closure

Transthoracic (TTE) and transesophageal (TEE) echocardiography represent the basic imaging tools for interatrial septum examination. Three dimensional (3D) TEE provides incremental information in the assessment of the interatrial septum. Further advanced echocardiography techniques using speckle tracking echocardiography are applied for sensitive volumetric and functional assessment of the heart chambers.&#160;

Transthoracic (TTE) and transesophageal echocardiography (TEE) is the standard imaging method for atrial septal defect (ASD) and patent foramen ovale ...

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3.5K Views.  Semmelweis University. Transthoracic (TTE) and transesophageal (TEE) echocardiography represent the basic imaging tools for interatrial septum examination. Three dimensional (3D) TEE provides incremental information in the assessment of the interatrial septum. Further advanced echocardiography techniques using speckle tracking echocardiography are applied for sensitive volumetric and functional assessment of the heart chambers. 

Video: Echocardiographic Evaluation of Atrial Communications before Transcatheter Closure

The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States 1. Since AF affects primarily elderly people, its prevalence increases parallel with age. As such, it is expected that 15.9 million Americans will be affected by the year 2050 2. Ischemic stroke occurs in 5% of non-anticoagulated AF patients each year. Current treatments for AF include rate control, rhythm control and prevention of stroke 3.
The American College of Cardiology, American Heart Association, and European Society of Cardiology currently recommended rate control as the first course of therapy for AF 3. Rate control is achieved by administration of pharmacological agents, such as &beta;-blockers, that lower the heart rate until it reaches a less symptomatic state 3. Rhythm control aims to return the heart to its normal sinus rhythm and is typically achieved through administration of antiarrhythmic drugs such as amiodarone, electrical cardioversion or ablation therapy. Rhythm control methods, however, have not been demonstrated to be superior to rate-control methods 4-6. In fact, certain antiarrhythmic drugs have been shown to be associated with higher hospitalization rates, serious adverse effects 3, or even increases in mortality in patients with structural heart defects 7. Thus, treatment with antiarrhythmics is more often used when rate-control drugs are ineffective or contraindicated. Rate-control and antiarrhythmic agents relieve the symptoms of AF, including palpitations, shortness of breath, and fatigue 8, but don't reliably prevent thromboembolic events 6.
Treatment with the anticoagulant drug warfarin significantly reduces the rate of stroke or embolism 9,10. However, because of problems associated with its use, fewer than 50% of patients are treated with it. The therapeutic dose is affected by drug, dietary, and metabolic interactions, and thus requires detailed monitoring. In addition, warfarin has the potential to cause severe, sometimes lethal, bleeding 2. As an alternative, aspirin is commonly prescribed. While aspirin is typically well tolerated, it is far less effective at preventing stroke 10. Other alternatives to warfarin, such as dabigatran 11 or rivaroxaban 12 demonstrate non-inferiority to warfarin with respect to thromboembolic events (in fact, dabigatran given as a high dose of 150 mg twice a day has shown superiority). While these drugs have the advantage of eliminating dietary concerns and eliminating the need for regular blood monitoring, major bleeding and associated complications, while somewhat less so than with warfarin, remain an issue 13-15.
Since 90% of AF-associated strokes result from emboli that arise from the left atrial appendage (LAA) 2, one alternative approach to warfarin therapy has been to exclude the LAA using an implanted device to trap blood clots before they exit. Here, we demonstrate a procedure for implanting the WATCHMAN Left Atrial Appendage Closure Device. A transseptal cannula is inserted through the femoral vein, and under fluoroscopic guidance, inter-atrial septum is crossed. Once access to the left atrium has been achieved, a guidewire is placed in the upper pulmonary vein and the WATCHMAN Access Sheath and dilator are advanced over the wire into the left atrium. The guidewire is removed, and the access sheath is carefully advanced into the distal portion of the LAA over a pigtail catheter. The WATCHMAN Delivery System is prepped, inserted into the access sheath, and slowly advanced. The WATCHMAN device is then deployed into the LAA. The device release criteria are confirmed via fluoroscopy and transesophageal echocardiography (TEE) and the device is released.

The accompanying video describes a procedure for percutaneous placement of the WATCHMAN Left Atrial Appendage (LAA) Device. The WATCHMAN is a nitinol device designed to be permanently implanted at, or slightly distal to, the opening of the left atrial appendage (LAA) to trap blood clots before they exit the LAA, preventing thromboembolic stroke.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States 1. Since AF affects primarily ...

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope 4, 5. Patients with AF have a five-fold higher risk of stroke 6.
Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% 7. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range 8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug 8.
The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF 12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers 4. CA is a well-established treatment for AF symptoms 14, 15, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy 16.
Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation 17, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) 18. This device received the Conformit&eacute; Europ&eacute;enne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy 19.
Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding 20 or other warfarin-associated problems.
The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1 21. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Catheter ablation is combined with placement of the WATCHMAN Left Atrial Appendage Closure Device to prevent ischemic stroke in a patient with non-valvular atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and ...

Echocardiographic Assessment of the Right Heart in Mice

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential therapies. Given the expense and time involved in creating animal models of disease, it is critical that researchers have tools to accurately assess phenotypic expression of disease. Right ventricular dysfunction is the major manifestation of pulmonary hypertension. Echocardiography is the mainstay of the noninvasive assessment of right ventricular function in rodent models and has the advantage of clear translation to humans in whom the same tool is used. Published echocardiography protocols in murine models of PAH are lacking.
In this article, we describe a protocol for assessing RV and pulmonary vascular function in a mouse model of PAH with a dominant negative BMPRII mutation; however, this protocol is applicable to any diseases affecting the pulmonary vasculature or right heart. We provide a detailed description of animal preparation, image acquisition and hemodynamic calculation of stroke volume, cardiac output and an estimate of pulmonary artery pressure.

This article provides a protocol for the echocardiographic assessment of right ventricular size and pulmonary hypertension in mice. Applications include phenotype determination and serial assessment in transgenic and toxin-induced mouse models of cardiomyopathy and pulmonary vascular disease.

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential ...

Robotic Ablation of Atrial Fibrillation

Background: Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). During PVI an electrical conduction block between pulmonary vein (PV) and left atrium (LA) is created. This conduction block prevents AF, which is triggered by irregular electric activity originating from the PV. However, transmural atrial lesions are required which can be challenging. Re-conduction and AF recurrence occur in 20 - 40% of the cases. Robotic catheter systems aim to improve catheter steerability. Here, a procedure with a new remote catheter system (RCS), is presented. Objective of this article is to show feasibility of robotic AF ablation with a novel system. Materials and Methods: After interatrial trans-septal puncture is performed using a long sheath and needle under fluoroscopic guidance. The needle is removed and a guide wire is placed in the left superior PV. Then an ablation catheter is positioned in the LA, using the sheath and wire as guide to the LA. LA angiography is performed over the sheath. A circular mapping catheter is positioned via the long sheath into the LA and a three-dimensional (3-D) anatomical reconstruction of the LA is performed. The handle of the ablation catheter is positioned in the robotic arm of the Amigo system and the ablation procedure begins. During the ablation procedure, the operator manipulates the ablation catheter via the robotic arm with the use of a remote control. The ablation is performed by creating point-by-point lesions around the left and right PV ostia. Contact force is measured at the catheter tip to provide feedback of catheter-tissue contact. Conduction block is confirmed by recording the PV potentials on the circular mapping catheter and by pacing maneuvers. The operator stays out of the radiationfield during ablation. Conclusion: The novel catheter system allows ablation with high stability on low operator fluoroscopy exposure.

Pulmonary vein isolation (PVI) with an ablation catheter is a curative treatment for atrial fibrillation (AF). Robotic catheter systems aim to improve catheter steerability. Here, a procedure with a new robotic catheter system is presented. The goal of the procedure is electrical block between pulmonary vein and left atrium.

Background: Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). During PVI an electrical conduction block between ...

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed in mice is high. Phenotypic characterization of these mouse models also requires the examination of cardiac function and morphology. Echocardiography and magnetic resonance imaging (MRI) are commonly used approaches to characterize cardiac function and morphology in mice. Echocardiographic and MRI equipment specialized for use in small rodents is&#160;expensive and requires a dedicated space. This protocol describes cardiac measurements in mice using a clinical echocardiographic system with a 15 MHz human vascular probe. Measurements are performed on anesthetized adult mice. At least three image sequences are recorded and analyzed for each animal in M-mode in the parasternal short-axis view. Afterwards, cardiac histological examination is performed, and cardiomyocyte diameters are determined on hematoxylin-eosin- or wheat germ agglutinin (WGA)-stained paraffin sections. Vessel density is determined morphometrically after Pecam-1 immunostaining. The protocol has been applied successfully to pharmacological studies and different genetic animal models under baseline conditions, as well as after experimental myocardial infarction by the permanent ligation of the left anterior descending coronary artery (LAD). In our experience, echocardiographic investigation is limited to anesthetized animals and is feasible in adult mice weighing at least 25 g.

Echocardiographic examination is frequently used in mice. Expensive high-resolution ultrasound devices have been developed for this purpose. This protocol describes an affordable echocardiographic procedure combined with histological morphometric analyses to determine cardiac morphology.

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed ...

Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV diastolic function is rarely quantified in experimental studies. This might be due to technical difficulties in the visualization of the RV in the apical four-chamber view in rodents. Here we describe two positions facilitating the visualization of the apical four-chamber view in mice to assess the RV diastolic function.
The apical four-chamber view is enabled by tilting the mouse fixation platform to the left and caudally (LeCa) or to the right and cranially (RiCr). Both positions provide images of comparable quality. The results of the RV diastolic function obtained from two positions are not significantly different. Both positions are comparably easy to perform. This protocol can be incorporated into published protocols and enables detailed investigations of the RV function.

Here we describe and compare two positions for obtaining the apical four-chamber view in mice. These positions enable the quantification of the right ventricular function, provide comparable results, and can be used interchangeably.

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV ...

Transthoracic Echocardiographic Examination in the Rabbit Model

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to that of humans and that of other large animal models such as dogs and pigs. However, the rabbit model has the additional advantage of lower maintenance costs compared to other large animal models. The longitudinal evaluation of cardiac function using echocardiography, when appropriately implemented, is a useful methodology for preclinical assessment of novel therapies for heart failure with reduced ejection fraction (e.g. cardiac regeneration). The correct use of this non-invasive tool requires the implementation of a standardized examination protocol following international guidelines. Here we describe, step by step, a detailed protocol supervised by veterinary cardiologists for performing echocardiography in the rabbit model, and demonstrate how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Here we describe, step by step, a detailed protocol for performing echocardiography in the rabbit model. We show how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to ...

Echocardiographic Assessment of Cardiac Anatomy and Function in Adult Rats

The use of experimental animal models has become crucial in cardiovascular science. Most studies using rodent models are focused on two-dimensional imaging to study the cardiac anatomy of the left ventricle and M-mode echo to assess its dimensions. However, this could limit a comprehensive study. Herein, we describe a protocol that allows an assessment of the heart chamber size, left ventricular function (systolic and diastolic) and valvular function. A conventional medical ultrasound machine was used in this protocol and different echo views were obtained through left parasternal, apical and suprasternal windows. In the left parasternal window, the long and short axis were acquired to analyze left chamber dimensions, right ventricle and pulmonary artery dimensions, and mitral, pulmonary and aortic valve function. The apical window allows the measurement of heart chamber dimensions and evaluation of systolic and diastolic parameters. It also allows Doppler assessment with detection and quantification of heart valve disturbances (regurgitation or stenosis). Different segments and walls of the left ventricle are visualized throughout all views. Finally, the ascending aorta, aortic arch, and descending aorta can be imaged through the suprasternal window. A combination of ultrasound imaging, Doppler flow and tissue Doppler assessment have been obtained to study cardiac morphology and function. This represents an important contribution to improve the assessment of cardiac function in adult rats with impact for research using these animal models.

A non-invasive protocol for transthoracic echocardiography assessment of cardiac anatomy and function for adult rats is presented in the current study. The heart valves, all four cardiac chambers and the ascending aorta, aortic arch and descending aorta are studied in detail.

The use of experimental animal models has become crucial in cardiovascular science. Most studies using rodent models are focused on two-dimensional ...

Evaluation of Capnography Sampling Line Compatibility and Accuracy when Used with a Portable Capnography Monitor

Capnography is commonly used to monitor patient&#8217;s ventilatory status. While sidestream capnography has been shown to provide a reliable assessment of end-tidal CO2 (ETCO2), its accuracy is commonly validated using commercial kits composed of a capnography monitor and its matching disposable nasal cannula sampling lines. The purpose of this study was to assess the compatibility and accuracy of cross-paired capnography sampling lines with a single portable bedside capnography monitor. A series of 4 bench tests were performed to evaluate the tensile strength, rise time, ETCO2 accuracy as a function of respiratory rate, and ETCO2 accuracy in the presence of supplemental O2. Each bench test was performed using specialized, validated equipment to allow for a full evaluation of sampling line performance. The 4 bench tests successfully differentiated between sampling lines from different commercial sources and suggested that due to increased rise time and decreased ETCO2 accuracy, not all nasal cannula sampling lines provide reliable clinical data when cross-paired with a commercial capnography monitor. Care should be taken to ensure that any cross-pairing of capnography monitors and disposable sampling lines is fully validated for use across respiratory rates and supplemental O2 flow rates commonly encountered in clinical settings.

The goal of this study was to evaluate the accuracy of capnography sampling lines used in conjunction with a portable bedside capnography monitor. Sampling lines from 7 manufacturers were evaluated for tensile strength, rise time, and ETCO2 accuracy as a function of respiratory rate or supplemental oxygen flow rate.

Capnography is commonly used to monitor patient&#8217;s ventilatory status. While sidestream capnography has been shown to provide a reliable assessment ...

Repetitive Blood Sampling from the Subclavian Vein of Conscious Rat

Rats are widely used in pharmacokinetics (PK) and toxicokinetic (TK) studies that need to collect a certain amount of blood at specific time points to detect drug exposure. The rat blood sampling method determines the quality of the plasma and further affects the precision of the test results. The subclavian vein blood collection method described in this protocol collects blood samples repeatedly in the conscious state of animals to meet the needs of PK and TK tests. The skills of restraint handling and appropriate procedure of needle incision ensure the success rate of blood collection. It is easy to operate while ensuring the quality of plasma and at the same time catering to animal welfare. However, this method requires skilled operation, and an improper one may cause animal weakness, pain, lameness, and even mortality. The current method has been used in the testing facility for a 4-week oral toxicity study in Sprague Dawley (SD) rats with TK. The maximum amount of blood collected within 24 h did not exceed 20% of the animal's total blood. The animals' body weight was more than 200 g for males and females. The data showed that the animals' bodyweight increased steadily every week, and the clinical observation was normal after repetitive sample collection.

The present protocol describes a simple and efficient method for collecting blood from the subclavian vein in rats. It enables rapid, timely, and easily identifiable sampling without anesthesia and obtains high-quality blood through repetitive sample collection.

Rats are widely used in pharmacokinetics (PK) and toxicokinetic (TK) studies that need to collect a certain amount of blood at specific time points to ...