ORIGINAL RESEARCH ARTICLE Assessment of short forms of recurrent atrial extra systoles by echocardiography with left atrial strain in ambulatory patients without organic cardiopathy Evaluación de formas cortas de extrasístoles auriculares recurrentes mediante ecocardiografía con deformación auricular izquierda en pacientes ambulatorios sin cardiopatía orgánica José M. Soler1*, Gemma García-Parés2, Oliver Valero3, Antonio Berruezo4, Victor J. Yuste5, and María Antonia Baltrons5* 1 Cardiology Department, Hospital Nostra Senyora de Meritxell, Andorra la Vella, Andorra; 2Psychiatrist Mental Health Department, Hospital Nostra Senyora de Meritxell. Andorra la Vella, Andorra; 3Statistical Department, Universitat Autònoma de Barcelona Barcelona, Spain; 4Cardiology Department, Heart Institute, Centro Médico Teknon, Barcelona, Spain; 5Cell Death, Senescence and Survival Group, Departament de Bioquímica i Biologia Molecular Universitat Autònoma de Barcelona, Barcelona, Spain; 6Institut de Neurociències, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Abstract Aim: To analyse the potential usefulness and clinical relevance of the assessment by echocardiography with left atrial strain, based on the myocardial atrial deformation curves with speckle-tracking velocity vector imaging (VVI), in the analysis of short- form recurrent atrial extra systoles in ambulatory patients not suffering from organic cardiopathy. Methods: We designed a descriptive, prospective, and observational study including 270 patients between the ages of 18 and 75 assessed during an outpatient cardiology consultation attended due to palpitations over a period of two years. Using ambulatory electrocardio- graphic monitoring, we selected cases with short forms of repetitive atrial extrasystole, isolated or recurrentatrial fibrillation and a control group formed by those patients without repetitive ectopia. All patients underwent a thorough echocardiograph- ic study during their first cardiological visit. Results: The analysis of the dynamic curves segmental deformation generated after an atrial extrasystole can reveal different points of origin of the extrasystole and detect specific anatomical alterations in the interatrial conduction at the level of the Bachmann’s fascicle showing different models of electro anatomical activation possibly involved in the appearance of repetitive forms. Higher values of dyssynchrony between the septal and lateral wall and elongation in the time of interatrial electromechanical conduction could also be related to the existence of repetitive ec- topic beats. Conclusions: Our ambulatory study employing the left atrial longitudinal strain, particularly in its segmental analysis, provides new insights into its the usefulness and potential clinical relevance. Keywords: Premature atrial contractions. Short atrial runs. Paroxysmal atrial fibrillation. Left atrial strain. Left atrial dyssyn- chrony. *Correspondence: Date of reception: 22-11-2021 Available online: 26-10-2022 José Miguel Soler Date of acceptance: 05-05-2022 Arch Cardiol Mex. 2023;93(2):172-182 E-mail: josepmiquel.soler@gmail.com DOI: 10.24875/ACM.21000368 www.archivoscardiologia.com 1405-9940 / © 2022 Instituto Nacional de Cardiología Ignacio Chávez. Published by Permanyer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 172 J.M. Soler et al. New left atrial strain utilities Resumen Objetivo: Analizar la utilidad y relevancia clínica de la evaluación mediante ecocardiografía basada en las curvas de deformación auricular miocárdica con imágenes vectoriales de velocidad (VVI) de speckle-tracking, en el análisis de las extrasístoles auricu- lares recurrentes de corta duración en pacientes ambulatorios sin cardiopatía orgánica. Métodos: Se diseñó un estudio descrip- tivo, prospectivo y observacional que incluyó a 270 pacientes de entre 18 y 75 años evaluados durante una consulta externa de cardiología a la que acudieron por palpitaciones durante un periodo de dos años. Mediante el uso de monitorización electrocar- diográfica ambulatoria, se seleccionaron casos con formas cortas de extrasistolia auricular repetitiva, fibrilación auricular aislada o repetitiva y un grupo control formado por aquellos pacientes sin ectopia repetitiva. Todos los pacientes se sometieron a un estudio ecocardiográfico exhaustivo durante su primera visita cardiológica. Resultados: El análisis de las curvas dinámicas de deformación segmentaria generadas tras un extrasístole auricular diferentes modelos de activación electroanatómica posiblemen- te implicados en la aparición de formas repetitivas. Valores mayores de disincronía entre la pared septal y lateral y el alarga- miento en el tiempo de conducción electromecánica intraauricular pudieran también relacionarse con la existencia de latidos ectópicos repetitivos. Conclusiones: Nuestro estudio ambulatorio empleando la deformación longitudinal auricular izquierda, particularmente en su análisis segmentario, proporciona nuevas perspectivas sobre su utilidad y potencial relevancia clínica. Palabras clave: Extrasístoles auriculares. Salvas de extrasistolia auricular. Fibrilación auricular paroxística. Curvas de de- formación auricular izquierda. Disincronía auricular izquierda. Introduction in various population groups although this seems to be an independent risk factor similar to high-density extra- Palpitations are one of the most common reasons for systoles5 with similar prognostic implications in the gen- consulting a cardiologist, together with chest pain, dys- eral population6. However, study of left and right atrial pnea and side effects of medication. The psychosomatic function has continued to advance, fundamentally at the etiology is usually the most common in the absence of expense of the echography-doppler with myocardial de- structural heart damage and anxiety is probably the most formation technology (Strain), and new electrophysiologi- common non-cardiac cause1. The presence of any type cal mapping systems usually used in tertiary hospitals of tachyarrhythmia is the most common form in patients and for mainly investigational and therapeutic purposes. with heart disease, highlighting in importance the per- Classic concepts related to left atrial function based sistent forms mostly of ventricular origin and some atrial on the electrocardiography and the basic echocardiog- forms, particularly atrial fibrillation and atrial flutter due to their frequency, possible complications and different raphy-doppler were developed, with the aim of quanti- treatment alternatives. An echocardiography is essential tatively defining the adaptive responses to “stress” for proper initial diagnosis stratification, together with an factors of the wall, promoters of a series of reactions accurate clinical history, electrocardiographic analysis to variations in pressure and/or volume leading to struc- and outpatient monitoring systems, while the availability tural, functional, electrical, metabolic and neurohor- of state-of-the-art equipment should make an additional monal remodeling7. The atrial extra systole interferes contribution to this first diagnostic and prognostic ap- with the atrial-ventricular filling sequence and its dura- proach and subsequent therapeutic decisions2. tion and frequency determine changes to the intra-au- In recent decades, significant advances have been ricular pressure/volume promoting this remodeling and made in the knowledge and treatment options for atrial its consequences. Strain values in the atrial reservoir fibrillation and flutter given its associated morbidity and phase during the left ventricular systole have proven mortality in certain risk groups. Various physio patholog- useful for the study of the left ventricular diastolic func- ical mechanisms involved in the triggering, maintenance tion, and its early dysfunction8. Short forms of recurrent and concluding of the arrhythmia have been checked, atrial arrhythmias could either alter it directly or act as and the risk factors involved in the genesis including a marker of any type of disorder affecting diastolic frequent atrial extra systoles appear to significantly influ- function. In addition, their possible association as an ence the apparently healthy general population3,4. independent factor of cardiovascular mortality or for We know less about the presence of recurrent atrial any reason in the long-term follow-up9, the frequently bursts, frequently excluded in Holter analyses that are asymptomatic presence, and the close association with more focused on the quantification of supraventricular hypertension, enhance the value of advanced echocar- extra systoles and the appearance of atrial fibrillation (AF) diography in primary cardiology. 173 Arch Cardiol Mex. 2023;93(2) Our study recruited patients with low comorbidity and follow-up). We studied 270 patients divided into the no evidence of structural heart disease that strength- following groups: ens the independent role of atrial extra systoles and Without repetitive atrial forms (control group) (78 pa- forms of short atrial tachyarrhythmia in relation to left tients), RUNs (162 patients), Isolated PAF (7 patients) atrial function parameters. Through the analysis of the and Recurrent PAF (23 patients). left atrial strain using 2D technology we try to obtain All patients received antihypertensive therapy if nec- useful parameters to identify patients with greater risk essary, with ACE inhibitors or ARA II adding flecainide of suffering more severe forms of atrial arrhythmia. and/or beta-blockers at intermediate doses in RUNs cases or PAF cases. 77% of patients with PAF relapsed Materials and methods and underwent selective ablation of pulmonary veins. Only 13% of patients were controlled with medication Patient selection during the follow-up period. None of the patients with RUNs had clinical worsening or the appearance of PAF Patients between 18-75 (mean age of 60) years old in the follow-up holters. The programming of the fol- with palpitations from an outpatient cardiology unit over low-up three-day holters was carried out according to a period covering July 2019 to September 2021, who had the symptomatic and ambulatory electrocardiographic attended on their own decision or were referred by their evolution. referring family doctor or by our hospital. All individuals were subject to a complete medical history review, as well as an examination including a psychological assess- Clinical history ment questionnaire, electrocardiogram, 3-day Holter and The usual face to face medical history data was ob- echocardiogram. Structural heart disease was ruled out tained at each in-person medical appointment including in all subjects following the necessary complementary demographic data and a simple psychiatric question- tests required by the clinic and patients were excluded naire: The Hospital Anxiety and Depression Scale if they had previously been diagnosed with any of the (HADS) provides fourteen multiple-choice questions re- following atrial flutter and/or fibrillation, fulguration or lating to states of anxiety and depression with subscales atrial ablation, ventricular arrhythmias in bursts or more, based on different scores, considering values over 11 basal electrocardiograph alterations as well as any de- as anxiety or depression. These subscales have also gree of atrial-ventricular blocking, complete blocking of proven useful as a measure of the severity of emotional the left branch, coronary heart disease, myocardiopa- disorders in medical research, enabling more compre- thies, any type of stenotic valve disease or valve regur- hensive care for the patient. The blood pressure mea- gitation more significant than mild, pericardium diseases, pacemakers, atrial surgery renal failure, known neoplas- surement was taken at least twice during the consultation tic disease and patients with a psychiatric disorder. In after five minutes of rest in the decubitus position with this study, we selected patients who were not suffering a manual cuff sensing the left brachial artery and vari- from organic heart disease, while avoiding the effects of ous measurements taken on an outpatient basis or by immaturity and aging on left atrial function that would the family doctor. We use the classification from the result in a less homogeneous study group and less re- American Heart Association (AHA) from 2018, which producible results10. In addition, with more advanced considers normal values less than 120/80 mmHg, ele- ages we assume a greater comorbidity, fundamentally vated blood pressure as values between 120-129 and in relation to a more developed hypertension and diabe- below 80 mmHg, stage 1 hypertension with values 130- tes with greater impairment of diastolic function. 139/80-89 mmHg, stage 2 hypertension with values of The study population comprised those patients who 140 or over/90 or over, retaining the values of presented palpitations with no repetitive ectopic atrial 140/90 mmHg as a cut-off point for the classification of forms, patients with short-form recurrent attacks (RUNs) embolic and cardiovascular risk CHA2DS2-VASc. Pa- as well as at least four beats of less than thirty seconds tients were considered diabetic if they presented limit in duration and forms of paroxysmal atrial fibrillation values after fasting of 126 mg/dl (7 mmol/l) and no sub- (PAF) with a duration greater than thirty seconds and jects were being treated with insulin. Body surface area less than seven days, isolated (a single episode) or values were considered normal up to 1.9 m2 in men and repetitive (more than one episode during subsequent 1.6 m2 in women. 174 J.M. Soler et al. New left atrial strain utilities Electrocardiogram dimensions, volumes and mass. The diastolic function study focused on the septal E/e’ values obtained with An electrocardiogram was performed on all patients, the tissue doppler with a cut-off value > 15 associated Schiller AT-10 plus with 12 leads with automatic analysis with an increase in left ventricular filling pressure and including P wave duration (ms), S wave in V1 (mV) re- the attainment of indexed left atrium volumes. The max- sulting from the correlation between the amplitude of imum and minimum 2D volumes were determined using terminal deflection multiplied by its duration (10) and Simpson’s biplane method. The 3D volumes were ob- Sokolov-Lyon criteria (mV). The electromechanical dis- tained using the real-time phased array probe with a persion is calculated manually by subtracting the min- sequence of two beats in apical four-chamber projection imum P wave duration value from its maximum value. focused on the left atrium tracing the contours manually Patients with bursts of atrial extrasystoles or atrial fibril- during the diastole before and after the atrial contraction lation were reported. Recordings were taken at a ve- (A wave) and in the systole just before the opening of locity of 25 mm/s and a voltage of 10 mm/mV by the the mitral valve. No geometric assumptions were made. same investigator. Finally, maximum tricuspid regurgitation velocity values were recorded using a continuous doppler. Outpatient electrocardiographic recording For the study of the longitudinal myocardial defor- (Holter) mity of the left atrial wall we used the Siemens e Sie VVI Velocity Vector Imaging Technology 2D speckle At the outset, all patients underwent continuous tracking software using two consecutive beats be- Holter monitoring over 3 days with DMS CardioScan II tween 30 and 90 frames per cycle in the apical Premier and NorthEast Monitoring Inc HE/LX analysis four-chamber projection, making a single contour of 6.0C Enhanced devices with all the recordings being the endocardium and avoiding the entry of the pulmo- checked manually. This was followed in the consultan- nary veins and the left appendage. We preselected cy with clinical and electrocardiographic tests, and fur- the division of the atrium into three zones: septal, ther Holter monitoring was carried out as decided by lateral and posterior eliminating the latter from the the cardiologist. Short forms of atrial extra systole were analysis thus automatically obtaining the segmental considered as the existence of four or more beats with strain curves in percentage/time, the global strain, a duration of less than thirty seconds and paroxysmal global reservoir strain and the maximum longitudinal atrial fibrillation with periods of greater arrhythmia of up strain peaks of the segmental reservoir (PLAS). We to seven days. The existence or lack of atrial and/or also recording the average value of the walls and the ventricular extra systoles was noted, considering a lateral wall independently, the left ventricular ejection slight incidence to be less than 1% of the beats. A check fraction (emptying), the time dispersion asynchrony was performed on whether the arrhythmia appeared on from the start of the electrocardiograph R wave and one, two or three days. We included mean frequency the maximum longitudinal strain peaks and the maxi- values and SDANN in the study in relation to the mum and minimum volumes. The percentage values time-related variability of the RR intervals with param- of the active atrial contraction were obtained manually eters related to the function of the autonomic nervous from the graphs of the strain curves. We also calcu- system. lated the electromechanical conduction interval of the atrium (PA-DTI) measuring the time in milliseconds between the start of the electrocardiograph P wave Echocardiography and the displacement of the lateral wall just below the The recordings were taken by the same expert cardi- posterior mitral annulus in the maximum peak of the ologist with an official qualification in advanced echocar- A wave for atrial contraction. Finally, we established diography and having performed more than three the wall stiffness index based on the coefficient ob- thousand atrial myocardial deformation studies (atrial tained between the value of E/e’ with respect to the strain). A Siemens SC 2000ultrasound was used, soft- reservoir strain (LAst). To obtain atrial strain images, ware version 5.1, year 2018, with sensors 4V1c (1.25-4.5 we tried to achieve an apical four-chamber plane fo- Mhz for 2D-doppler-transthoracic strain study) and 4Z1c cused on the left atrium while avoiding errors involving (1.5-3.5 Mhz for real-time 3D volumetric study). The cutting the posterior wall and overlapping of the start guidelines of the American Society of Echocardiography of the aortic outflow tract. The qualitative image tried (ASE) were followed to obtain the indexed left ventricular from the start to obtain a subjective harmony 175 Arch Cardiol Mex. 2023;93(2) recording two atrial strain results in all patients select- P-wave duration were relevant between the recurrent ing the results that offered the greatest global strain forms with respect to the isolated forms and the RUNs. and lower asynchrony. The studies used a Radiant Likewise, the dispersion of the P wave was greater in DICOM Viewer device for their subsequent review and the recurrent forms with respect to the RUNs (Ta- were repeated in case of doubt within a maximum of ble 3 Supplementary) but its significance is debatable one month after the first recording. All the studies to power only a marker of electrical dispersion without were performed before ablation therapy. functional translation. In addition, the left atrial global strain, peak longitudinal average atrial strain, peak atrial contraction strain and left Statistical analysis atrial ejection fraction are significantly reduced in the To compare clinical and demographic characteristics, RUNs group and recurrent forms of PAF in comparison electrocardiographic variables, Holter variables and with the control group only in the bivariate statistical mod- echocardiographic variables between groups we used el. The same thing happened in the percentage of dys- X2 tests for categorical variables and ANOVA for quan- synchrony and electromechanical left atrial conduction. titative variables (or Kruskal-Wallis test for variables Intriguingly, in our study, we observed in a non-proto- with non-normal distribution). Post-hoc pairwise com- colized way some models of basal dyssynchrony and parisons were computed using Bonferroni’s correction. dynamic image sequences after an atrial extra systole Two multivariate logistic regression models were ad- that suggest different pathogenesis at the beginning of justed to compare cases with controls and recurrent repetitive forms. Figure 1 suggest the origin of extra PAF with controls. All variables with a p-value < 0.1 in systole at the level of the pulmonary veins whose ar- the bivariate analysis were included as covariates. The rhythmogenic potential is classically defined and in ad- final model was obtained using a backward variable dition, there is an anatomical alteration in intratrial selection method. Odds ratio with their respective 95% conduction involving in some way the Bachmann’s fas- confidence intervals were obtained. Statistical analyses ciculus. This patient presented atrial fibrillation just be- were performed with the SAS system version 9.4 (SAS fore the ablation, during catheter manipulation and Institute Inc., Cary, North Carolina, USA). Statistical showed RUNs, and PAF in the follow-up Holters not significance level was set at α = 0.05. seen in the initial analysis. Figure 2 show the initial se- All patients signed a statement of informed consent and quences of extra systoles with changes in longitudinal the study respected the Declaration of Helsinki and was and segmentary strain that guide on the functional state approved by with the ethic local hospital committee. of the left atrium and its adaptation mechanisms. Results Discussion The clinical and socio-demographic characteristics of Initial electrocardiographic analysis by a specialist the 270 patients are shown in Table 1 and the echo- can also provide relevant data even when anxiety ap- cardiographic variables in Table 2. As previously de- pears to be the single cause of palpitations11 specially scribed in methods section, the RUNs group included the values of duration and dispersion of the p wave. the largest number of patients (n = 162) and the first In our study, we selected patients were not displaying aim of our study was to compare this group with de organic cardiopathy with short forms of atrial arrhyth- control group. Although apparently significant differenc- mia that could raise other arrhythmia-inducing causal es were observed between RUNs and control group, in factors such as anatomical abnormalities and presence the multivariate study only older age, greater left atrial of focal areas of fibrosis undetectable with traditional volume and higher CHAD2DS2-VASc score were sta- imaging methods. Our results show that left atrial diam- tistically significant (Table 1 Supplementary). Although eter and volumes are the most significative variables, only marginally statistically significant, anxiety was in suggesting transitory and reversible changes during the greater percentage in control versus RUNs. In the mul- short left atrial arrythmias, indicating the potential pres- tivariate analysis between the controls and recurrent ence of sustained hidden atrial arrythmias, frequently PAF, only the age was significant (Table 2 Supplemen- undetectable by traditional Holter recordings. tary). Regard to the electrocardiogram, no significant In our work, higher values of dyssynchrony at 57 ms differences were observed between the control group and 6.5% with respect to the RR interval in atrial strain and the RUNs. However, the increased values in were associated with a higher risk of recurrent PAF. Other 176 J.M. Soler et al. New left atrial strain utilities Table 1. Patient characteristics and clinical evaluation Variable Control (n = 78) Runs (n = 162) Isolated PAF (n = 7) Recurrent PAF (n = 23) Age 53.9 ± 10.6* 63.0 ± 9.5 42.7 ± 18.0* 64.0 ± 8.5 I Gender – Female 60 (76.9%) 112 (69.1%) 2 (28.6%)* 10 (43.5%)* Married 68 (87.2%) 140 (86.4%) 4 (57.1%) 18 (78.3%) Secondary education 33 (42.3%)* 46 (28.4%) 1 (14.3%) 5 (21.7%) Active 65 (83.3%)* 90 (55.6%) 6 (85.7%) 9 (39.1%) * Immigrant 45 (57.7%) 100 (61.7%) 5 (71.4%) 19 (82.6%)* Anxiety 8.83 ± 3.95* 7.79 ± 3.89 9.43 ± 3.15 7.48 ± 3.75 Depression 5.08 ± 3.92 4.20 ± 3.49 4.14 ± 2.67 3.96 ± 2.90 Previous history of palpitations 31 (39.7%) 85 (52.5%) 3 (42.9%) 22 (95.7%)* I Complementary cardiac test 44 (56.4%)* 114 (70.4%) 4 (57.1%) 21 (91.3%)* Treatments 1.39 ± 0.84 1.51 ± 0.97 1.29 ± 1.38 2.26 ± 1.05* Intense sport 2 (2.6%) 4 (2.5%) 0 (0%) 2 (8.7%) Diabetes 6 (7.7%) 14 (8.6%) 1 (14.3%) 2 (8.7%) Thyroid 11 (14.1%) 28 (17.3%) 0 (0%) 3 (13.0%) OSAS 4 (5.1%) 16 (9.9%) 1 (10.7%) 3 (13.0%) Chronic obstructive bronchopathy 0 (0%)* 9 (5.6%) 0 (0%) 3 (13.0%)* No HT 43 (55.1%)* 48 (29.6%) 2 (28.6%) 3 (13.0%)* Elevated BP 12 (15.4%) 41 (25.3%) 1 (14.3%) 5 (21.7%) Hypertension Stage I 22 (28.2%)* 68 (42.0%) 3 (42.9%) 13 (56.5%)* Hypertension Stage II 1 (1.3%) 5 (3.1%) 1 (14.3%) 2 (8.7%) Ambulatory control BP 76 (97.4%) 154 (95.1%) 6 (85.7%) 20 (87.0%) Corporal surface 1.77 ± 0.21 1.79 ± 0.18 1.90 ± 0.23 1.85 ± 0.20 CHA 2‑ DS2‑VASc score 1.14 ± 0.66* 1.69 ± 0.88 0.86 ± 0.90* 2.13 ± 1.18* I Heredity 11 (14.1%) 36 (22.2%) 0 (0%) 3 (13.0%) Mean ± standard deviation for quantitative variables and n (percentage) for categorical variables. *Indicates statistically significant differences between the different groups and RUNs; Iindicates statistically significant differences between ISOLATED and RECURRENT PAF. RUNs: repetitive ectopi catrial forms; PAF: paroxysmal atrial fibrillation; OSAS: sleep apnea; BP: blood pressure; HT: hypertension. recent studies with population groups and methodology conduction time in reference to the electrocardiograph similar to ours, show the importance of left intra-atrial P wave in selected patients for pulmonary vein ablation dyssynchrony as a predictor of initial or recurrent atrial and a control group without a history of atrial fibrillation16. fibrillation proposing it as a first-line echocardiographic All patients underwent electro-anatomical mapping with variable even in patients without structural heart disease and the Carto system performing circumferential pulmonary in silent forms12-14. Recently, its use has also been con- vein insertion according to the standard protocol of the sidered by transesophageal echocardiography at the level center with additional ablation lines in areas of low volt- of the left atrial appendage in the assessment of emboli age (< 0.5mV). Compared to the control group, patients genic risk of patients with PAF15. with PAF had significantly lengthened conduction inter- Dinov and cols., showed different models of left atrial vals at the septal, lateral, anterior and posterior levels of activation after electromechanical mapping with tissue the left atrium while this not being the case at the level doppler at five different points, also including the lateral of the tricuspid annulus. With cut-off values of 55 ms, segment of the tricuspid annulus by measuring they were able to discriminate between the control group 177 Arch Cardiol Mex. 2023;93(2) Table 2. Echocardiographic variables Variable Control (n = 78) Runs (n = 162) Isolated PAF (n = 7) Recurrent PAF (n = 23) E/e’’ 7.97 ± 2.37* 9.12 ± 2.71 7.74 ± 2.32 8.72 ± 2.60 VRT 1.95 ± 0.50* 2.15 ± 0.57 1.87 ± 0.68 2.30 ± 0.48* Left atrial diameter 3.44 ± 0.66* 3.65 ± 0.66 3.87 ± 0.91 4.02 ± 0.64* LA vol min 8.59 ± 2.90* 10.58 ± 4.44 12.7 ± 7.70* 12.3 ± 5.89* LA vol max 2D 22.8 ± 5.37* 26.7 ± 8.13 31.3 ± 11.34* 32.0 ± 7.19* LA vol max 3D 25.4 ± 6.08* 30.9 ± 9.28 32.7 ± 10.0* 36.8 ± 9.42* Peak longitudinal averaged atrial strain (in %) 51.4 ± 23.9* 43.5 ± 21.7 51.7 ± 17.2 37.4 ± 15.3* Peak longitudinal lateral atrial strain (in %) 55.9 ± 28.7 50.2 ± 29.7 48.4 ± 13.2 41.9 ± 21.0* Peak atrial contraction strain (in %) –23.6 ± 11.0* –21.0 ± 7.55 –21.7 ± 9.46 –17.4 ± 6.13* Left atrial global strain (in %) 54.4 ± 25.0* 44.8 ± 20.4 41.0 ± 16.3 37.7 ± 15.8* Electromechanical left atrial conduction 125.8 ± 14.9 127.6 ± 16.6 134.0 ± 11.3* 149.7 ± 19.7* I Parietal stiffness (LAst) 0.19 ± 0.14* 0.25 ± 0.15 0.26 ± 0.20 0.28 ± 0.20* Dyssynchrony (in ms) 31.6 ± 29.3 46.2 ± 44.4 25.8 ± 32.0* 57.4 ± 36.8 Dyssynchrony (in %) 3.69 ± 3.54* 4.80 ± 4.08 2.71 ± 3.15 6.57 ± 5.15* I LV mass indexed 82.5 ± 23.6* 93.0 ± 28.2 91.1 ± 19.4 106.4 ± 24.9* Global longitudinal ventricular strain (in %) –21.5 ± 2.86 –21.9 ± 2.95 –20.9 ± 3.13 –21.7 ± 2.93 Left ventricular ejection fraction (in %) 62.6 ± 3.68 63.0 ± 3.81 60.0 ± 2.94 62.0 ± 3.84 The values are mean ± standard deviation. * Indicates statistically significant differences in the comparison with RUNs; Iindicates statistically significant differences between ISOLATED and RECURRENT PAF. RUNs: repetitive ectopic atrial forms; PAF: paroxysmal atrial fibrillation; VRT: velocity tricuspid regurgitation; LA: left atrial; Vol: volume; Max: maximum; 2D: two dimensional; 3D: three dimensional; LV: left ventricle. and PAF patients with 81.5% sensitivity and 82.8% spec- everyday cardiological practice19. Another recent article ificity, showing activation onset in the upper area of the using 3D speckle-tracking correlates these electro-ana- left atrium with delayed activation at the level of the mitral tomical concepts, dyssynchrony and delay in atrial con- annulus, suggesting a blockage in the Bachmann bundle duction in patients with PAF, verifying dyssynchrony in that connects the right atrium with the anterior-superior the early stages of atrial remodeling20. Values among the part of the left atrium, although genetically mediated normal population recorded a mean of 42 ms and 2% electrical and structural family variants may also promote relative to the RR intervals with negative prognostic im- these different behaviors17. A recent work also using plications in terms of the greater risk of global mortality, tissue Doppler in 98 patients with electrocardiographic atrial fibrillation and stroke mostly in females21. In sum- signs of to the existence of blockade of the Bachmann´s mary, changes in the sequence of electro-anatomi- fasciculus among whom many displayed hypertension cal-physiological mechanical activation can be suspected and some ischemic disease, obtained assynchrony val- with techniques based on the left atrial strain and can ues in relation by comparing the activation of the septal occur anywhere in the left atrium facilitating the re-entry and lateral wall thus obtaining cut-off values of 39+/-16 and appearance of repetitive forms22. ms18. Seven days Holter recordings were carried out Some studies have also shown the usefulness of left during the follow-up in symptomatic patients, resulting in atrial segmental longitudinal strain23, although with current 10% of patients with PAF, a similar result to that obtained software it requires offline expert analysis. Figures 1 and by us (11%). On the other hand, the works that have 2 show two examples of an extrasystole and the changes studied the electro-mechanical conduction times of the caused in the segmental left atrial deformation curves. atria with tissue Doppler techniques support the con- The relationship between the place of origin of PACs and cepts obtained by catheter mapping techniques helping the initiation of atrial fibrillation is well known24, but is not to establish cut-off values easily reproducible in usually taken into account in the routine assessment in 178 J.M. Soler et al. New left atrial strain utilities A B C D Figure 1. Global and segmental atrial strain with “gating” in the electrocardiograph R wave. Correlative frames that include an atrial extra systole and the different behavior of its longitudinal segmental deformation curves that suggest different points of origin of the arrhythmia and probably different pathogenesis. 55-Year-old female patient with elevated blood pressure treated with Angiotensin Converting Enzyme inhibitors, family history of ablated atrial fibrillation and atrial extra systole of moderate density, that was documented for the last two years not showing repetitive forms (control group) with clinical limitation to effort without obvious structural heart disease. The basal electrocardiogram showed no alterations to the P wave and the and the extrasystole was positive on the lower side and V1 with negativity in a VL suggestive of an origin in the posterior left superior pulmonary vein. (A) The basal echocardiogram showed no significant alterations or signs of delay in electro-mechanical activation or asynchrony. (B) shows the deformation curves of the septal, posterior and lateral walls during sinus rhythm, showing a maximum peak of positive longitudinal elongation. very predominant posterior aspect with slight asynchrony as regards the activation of the septal and lateral walls (18 ms) with reservoir strain values within normal ranges. During extra systole (C) we saw a decrease in global and segmental strain values with a reduction in the activation time of the posterior wall and a significant increase in asynchrony with respect to the septal and lateral walls. This suggests anisotropic conditions and a type of left intra- atrial block with delay in the activity of the basal segments possibly involving the Bachmann’s fascicle. In (D) we observe beats after the extra systole with a tendency to recover the initial global and segmental strain values. primary care. To our knowledge, these images are a new to the adverse remodeling of the left atrium. Several contribution to an understanding of the dynamic behavior studies with transthoracic and trans esophageal echo- of the curves of the segmental left atrial longitudinal cardiography have shown transitory alterations in the strain before, during and after a PAC. As they are not mechanical function of the left atrium and the append- cinematic sequences, there is a short time lag between age, with reversed atrial fibrillation even spontaneously the acquisition of each image that prevents rigorous with reduced Doppler velocity values fundamentally in quantitative evaluations. Dyssynchrony studies in the the atrial appendage. The duration of these alterations comparison of this type of curve based on the segmental depends on the length of the arrhythmia, the atrial diam- atrial strain peak show no significant differences in rela- eter, its wall stiffness in relation to structural changes of tion to the number of segments assessed (at least two). the atrial connective tissue and the underlying structural Another important aspect derived from our graphs is the heart disease25. stunning effect observed after PACs. Although we only At present, the software used in the atrial deforma- show two cases in a qualitative way, it could be related tion study is not specifically developed for it and 179 Arch Cardiol Mex. 2023;93(2) A B C Figure 2. 75-year-old patient, hypertensive with atrial extrasystole bursts and no evidence of atrial fibrillation with an electrocardiograph P wave of 122 ms and an electrocardiogram which showed slight left atrial dilation (35 ml/m2) and no increase in the electromechanical conduction time with asynchrony in the longitudinal tension between the septal and lateral walls (54 ms, 5% relative to the RR). (A) shows the basal recording; (B) is during the extrasystole with a slight increase in the asynchrony and the global strain initiating a sequence of several recurrent beats; (C) shows an increase in the global and segmental reservoir causing the disappearance of the asynchrony and equalising the wall tension values without active contraction. This suggests a homogeneous activation front without anatomical obstacle, with increased atrial pressure and adaptive stretching of the atrial wall. 180 J.M. Soler et al. New left atrial strain utilities adaptations are made to the model used in the left better understanding of the left atrial adaptation ventricle. Manufacturers should take into account the mechanisms. significant usefulness of studying dyssynchrony be- fore, during and after atrial arrhythmia, as well as the Acknowledgements stunning time, by creating cineloop sequences with easy-to-use quantitative values, as well as automati- The authors thanks to the medical secretaries, Liliana cally setting the study segment. Parietal muscles Santos and Svitlana Yiakoumpiv in database elabora- adapted to the anatomy of each patient through three-di- tion work, and the English editing performed by Patricia mensional echocardiography with tracking velocities Nally. adapted to the atrium, would all contribute to a great improvement in the study of these and other atrial Funding arrhythmias. This research has not received any specific grant from public, commercial, or non-profit sector agencies. Limitations of the study First, the control group is not really a healthy popula- Conflicts of interest tion because they felt some palpitations and the results are not extrapolatable for the asymptomatic general The authors declare that they have no conflicts of people. Moreover, it was also impossible to persuade interest. the volunteers for wearing the Holter for three days. Second, the software specially designed for exclusive Ethical disclosures use in the left atrium planned, based on the three-di- mensional anatomical analysis combining cine se- Protection of human and animal subjects. The quences and quantitative velocity-time analysis of the authors declare that no experiments were performed on maximum peaks of longitudinal deformation may be humans or animals for this study. useful for establishing earlier prognostic stratification in Confidentiality of data. The authors declare that these arrhythmias and their more appropriate clinical they have followed the protocols of their work center on management groups with long-term follow-up. The the publication of patient data. graphs only represent functional and qualitative value, Right to privacy and informed consent. The au- and their validity remains to be confirmed in subsequent thors have obtained the written informed consent of the studies carried out with programs developed for this patients or subjects mentioned in the article. The corre- purpose. Third, the echocardiograph study was carried sponding author is in possession of this document. out by only one expert, although intra-observer variabil- ity studies performed in the EACVI NORRE study and References in the BEFRI study reported an excellent intra-class 1. Barsky AJ, Cleary PD, Coeytaux RR, Ruskin JN. Psychiatric disorders in correlation coefficient26. Fourth, the electrocardiograph medical outpatients complaining of palpitations. J Gen Intern Med. values of the terminal forces of the P wave in V1 were 1994;96:306-13. 2. Wexler RK, Pleister A, Raman SV. Palpitations: Evaluation in the Primary carried out automatically by the equipment, which may Care Setting. Am Fam Physician. 2017;15:784-89. 3. Binici Z, Intzilakis T, Nielsen OW, Køber L, Sajadieh A. Excessive supra- result in greater interpretation errors than with the man- ventricular ectopic activity and increased risk of atrial fibrillation and ual analysis. Fifth, the low number of patients showing stroke. Circulation. 2010; 121:1904-11. 4. Patel A, Anugula D, Kanmanthareddy A, Urja P, Haddad TM, Alla V. atrial fibrillation does not permit to stablish a threshold Prognostic impact of premature atrial complexes in the general population: in the basal dyssynchrony analysis between control and A meta-analysis of observational studies. J Am Coll Cardiol. 2017;69:333. 5. Perez MV, Dewey FE, Marcus R, Ashley EA, Al-Ahmad AA, Wang PJ, et al. repetitive-PAF individuals. Electrocardiographic predictors of atrial fibrillation. Am Heart J. 2009;158:622-8. 6. Yamada S, Lin CY, Chang SL, Chao TF, Lin YJ, Lo LW, et al. Risk of Stroke in Patients With Short-Run Atrial Tachyarrhythmia. Stroke. 2017;48:3232-38. Conclusions 7. Casaclang-Verzosa G, Gersh BJ, Tsang TS. Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation. J Am Coll Cardiol. 2008;51:1-11. The dynamic curves of left atrial strain generated 8. Singh A, Addetia K, Maffessanti F, Mor-Avi V, Lang RM. LA Strain for after an extra systole allow to observe activation se- Categorization of LV Diastolic Dysfunction. JACC Cardiovasc Imaging. 2017; 10:735-43. quences that suggest their origin around the pulmonary 9. Murakoshi N, Xu D, Sairenchi T, Igarashi M, Irie F, Tomizawa T, et al. veins and in addition, they can show anatomical disor- Prognostic impact of supraventricular premature complexes in communi- ty-based health checkups: the Ibaraki Prefectural Health Study. Eur Heart ders in the interauricular conduction and an aid in the J. 2015;36:170-8. 181 Arch Cardiol Mex. 2023;93(2) 10. Lin K-K, Chen K-K, Li S, Cai MK, Yuan MJ, Wang YP, et al. Impaired 18. Seewöster T, Marinov K, Löbe S, Knopp H, Nedios S, Bollmann A, et al. Left Atrial Performance Resulting From Age. Related Atrial Fibrillation Is Abnormal pattern of left atrial activation and asynchronous conduction Associated With Increased Fibrosis Burden: Insights From a Clinical predicted the occurrence of new atrial fibrillation: evidences for Study Combining With an in vivo Experiment. Front. Cardiovasc. Med. Bachmann´s bundle block in atrial fibrillation pathophysiology. Europace. 2021;7:1-12. 2021;00:1-8. 11. O’Neal WT, Hammadah M, Sandesara PB, Almuwaqqat Z, Samman-Ta- 19. den Uijl DW, Gawrysiak M, Tops LF, Trines SA, Zeppenfeld K, hhan A, Gafeer MM, et al. The association between acute mental stress Schalij MJ, et al. Prognostic value of total atrial conduction time estima- and abnormal left atrial electrophysiology. J Cardiovasc Electrophysiol. ted with tissue Doppler imaging to predict the recurrence of atrial fibrilla- 2017;28:1151-57. tion after radiofrequency catheter ablation. Europace. 2011;13:1533-40. 12. Sebastian I. Sarvari, Kristina H. Haugaa, Thomas M. Stokke, Hamza Z. 20. Watanabe Y, Nakano Y, Hidaka T, Oda N, Kajihara K, Tokuyama T, et al. Ansari, Ida S. Leren, Finn Hegbom, et al. Strain echocardiographic as- Mechanical and substrate abnormalities of the left atrium assessed by sessment of atrial function predicts recurrence of atrial fibrillation. Eur 3-dimensional speckle-tracking echocardiography and electroanatomic Heart J. 2016;17:660-7. mapping system in patients with paroxysmal atrial fibrillation. Heart 13. Kawakami H, Ramkumar S, Nolan M, Wright L, Yang H, Negishi K, et al. Rhythm. 2015;12:490-97. Left atrial mechanical dispersion assessed by strain echocardiography 21. Karsum EH, Andersen DM, Modin D, Biering-Sørensen SR, Mogelvang R, as an independent predictor of new-onset atrial fibrillation: A case-control Jensen G, et al. The prognostic value of left atrial dyssynchrony measured study. J Am Soc Echocardiogr. 2019;32:1268-1276. by speckle tracking echocardiography in the general population. Int J 14. Solberg MG, Aagaard ES, Berge T, Roenningen PS, Enger S, Nygaard Cardiovasc Imaging. 2021;37:1679-88. S, et al. Left atrial dysfunction and dyssyncrony in paroxysmal atrial fi- 22. Van Campenhout M, Yaksh A, Kik Ch, de Jaegere PP, Yen Ho SY, brillation: data from the akershus cardiac examination 1950 study. Eur Maurits A, et al. Bachmann’s bundle: a key player in the development of Heart J. 2020;41. Supplement 2,79. atrial fibrillation? Circ Arrhythm Electrophysiol. 2013;6:1041-46. 15. Mao Y, Ma M, Yang Y, Yu Ch, Wang Y, Jiang R, et al. Left atrial appen- 23. Todaro MC, Choudhuri I, Belohlavek M, Jahangir A, Carerj S, Oreto L, dage mechanical dispersion provides incremental value for thromboem- et al. New echocardiographic techniques for evaluation of left atrial me- bolic risk stratification over CHA2DS2-VASc Score in nonvalvular atrial chanics. Eur Heart J Cardiovasc Imaging. 2012;13:973-84. fibrillation. Int J Cardiol. 2020;15:41-47. 24. Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, 16. Dinov B, Knopp H, Löbe S, Nedios S, Bode K, Schönbauer R, et al. et al. Spontaneous initiation of atrial fibrillation by ectopic beats origina- Patterns of left atrial activation and evaluation of atrial dyssynchrony in ting in the pulmonary veins. N Engl J Med. 1998;339:659-66. patients with atrial fibrillation and normal controls: Factors beyond the left 25. Khan IA, Atrial stunning basics and clinical considerations. Int J Cardiol. atrial dimensions. Heart Rhythm. 2016;13:1829-36. 2003;92:113-28. 17. Kalsto SM, Siland JE, Rienstra M, Christophersen IE. Atrial Fibrillation 26. Americo C, Pécora M, Janssen B, Parma G, Boggia J, Florio L. Left Genetics Update: Toward Clinical Implementation. Front Cardiovasc Med atrium strain by speeckle tracking: evaluation of its global and segmental 2019;6:127. reproducibility. Rev Urug Cardiol. 2019;34:248-55. 182