Left Atrial Markers in Diagnosing and Prognosticating Non-Ischemic Cardiomyopathies: Ready for Prime Time?
Corresponding Author
Mina M. Benjamin
Cardiology Division, Saint Louis University Hospital, St Louis, Missouri, USA
Correspondence: Mina M. Benjamin ([email protected])
Search for more papers by this authorMark G. Rabbat
Department of Cardiology, Loyola University Medical Center, Maywood, Illinois, USA
Search for more papers by this authorCorresponding Author
Mina M. Benjamin
Cardiology Division, Saint Louis University Hospital, St Louis, Missouri, USA
Correspondence: Mina M. Benjamin ([email protected])
Search for more papers by this authorMark G. Rabbat
Department of Cardiology, Loyola University Medical Center, Maywood, Illinois, USA
Search for more papers by this authorABSTRACT
The left atrium (LA) is pivotal in cardiac hemodynamics, serving as a dynamic indicator of left ventricular (LV) compliance and diastolic function. The LA undergoes structural and functional adaptations in response to hemodynamic stress, infiltrative processes, myocardial injury, and arrhythmic triggers. Remodeling of the LA in response to these stressors directly impacts pulmonary circulation, eventually leading to pulmonary capillary involvement, pulmonary artery hypertension, and eventually right ventricular failure. LA dysfunction and fibrosis also contribute to the future risk of atrial arrhythmias and mitral regurgitation. The parameters of LA size and function are being recognized as robust markers for the progression of several cardiac pathologies as well as important tools for prognostication. In this article, we briefly describe the different modalities and markers used to evaluate LA pathology in patients with nonischemic cardiomyopathies (NICM). We then provide an overview of the studies that compared the association of the different LA parameters with disease severity and future prognosis. We also identify the gaps in knowledge before these LA parameters make a case for clinical adoption.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
- 1I. Bytyci and G. Bajraktari, “Left Atrial Changes in Early Stages of Heart Failure With Preserved Ejection Fraction,” Echocardiography 33, no. 10 (2016): 1479–1487, https://doi.org/10.1111/echo.13306.
- 2M. M. Benjamin, N. Moulki, A. Waqar, et al., “Association of Left Atrial Strain by Cardiovascular Magnetic Resonance With Recurrence of Atrial Fibrillation Following Catheter Ablation,” Journal of Cardiovascular Magnetic Resonance 24, no 1. (2022): 3, https://doi.org/10.1186/s12968-021-00831-3.
- 3K. Kusunose, H. Motoki, Z. B. Popovic, J. D. Thomas, A. L. Klein, and T. H. Marwick, “Independent Association of Left Atrial Function With Exercise Capacity in Patients With Preserved Ejection Fraction,” Heart 98, no. 17 (2012): 1311–1317, https://doi.org/10.1136/heartjnl-2012-302007.
- 4A. Malagoli, L. Rossi, F. Bursi, et al., “Left Atrial Function Predicts Cardiovascular Events in Patients With Chronic Heart Failure With Reduced Ejection Fraction,” Journal of the American Society of Echocardiography 32, no. 2 (2019): 248–256, https://doi.org/10.1016/j.echo.2018.08.012.
- 5M. Guazzi and R. Naeije, “Right Heart Phenotype in Heart Failure with Preserved Ejection Fraction,” Circulation: Heart Failure 14, no. 4 (2021): e007840, https://doi.org/10.1161/CIRCHEARTFAILURE.120.007840.
- 6R. M. Inciardi, A. Bonelli, T. Biering-Sorensen, et al., “Left Atrial Disease and Left Atrial Reverse Remodelling Across Different Stages of Heart Failure Development and Progression: A New Target for Prevention and Treatment,” European Journal of Heart Failure 24, no. 6 (2022): 959–975, https://doi.org/10.1002/ejhf.2562.
- 7P. Hedberg, J. Selmeryd, J. Leppert, and E. Henriksen, “Left Atrial Minimum Volume Is More Strongly Associated With N-Terminal Pro-B-Type Natriuretic Peptide Than the Left Atrial Maximum Volume in a Community-Based Sample,” International Journal of Cardiovascular Imaging 32, no. 3 (2016): 417–425, https://doi.org/10.1007/s10554-015-0800-1.
- 8F. Pathan, N. D'Elia, M. T. Nolan, T. H. Marwick, and K. Negishi, “Normal Ranges of Left Atrial Strain by Speckle-Tracking Echocardiography: A Systematic Review and Meta-Analysis,” Journal of the American Society of Echocardiography 30, no. 1 (2017): 59–70, https://doi.org/10.1016/j.echo.2016.09.007.
- 9A. Venkateshvaran, H. O. Tureli, U. L. Faxen, L. H. Lund, E. Tossavainen, and P. Lindqvist, “Left Atrial Reservoir Strain Improves Diagnostic Accuracy of the 2016 ASE/EACVI Diastolic Algorithm in Patients With Preserved Left Ventricular Ejection Fraction: Insights From the KARUM Haemodynamic Database,” European Heart Journal - Cardiovascular Imaging 23, no. 9 (2022): 1157–1168, https://doi.org/10.1093/ehjci/jeac036.
- 10R. C. Rimbas, R. E. Dulgheru, and D. Vinereanu, “Methodological Gaps in Left Atrial Function Assessment by 2D Speckle Tracking Echocardiography,” Arquivos Brasileiros De Cardiologia 105, no. 6 (2015): 625–636, https://doi.org/10.5935/abc.20150144.
- 11M. M. Benjamin, M. S. Munir, P. Shah, et al., “Comparison of Left Atrial Strain by Feature-Tracking Cardiac Magnetic Resonance With Speckle-Tracking Transthoracic Echocardiography,” International Journal of Cardiovascular Imaging 38, no. 6 (2022): 1383–1389, https://doi.org/10.1007/s10554-021-02499-3.
- 12G. E. Mandoli, M. C. Pastore, M. C. Procopio, et al., “Unveiling the Reliability of Left Atrial Strain Measurement: A Dedicated Speckle Tracking Software Perspective in Controls and Cases,” European Heart Journal–Imaging Methods and Practice 2, no. 1 (2024): qyae061, https://doi.org/10.1093/ehjimp/qyae061.
- 13J. H. Koh, L. K. E. Lim, Y. K. Tan, et al., “Assessment of Left Atrial Fibrosis by Cardiac Magnetic Resonance Imaging in Ischemic Stroke Patients Without Atrial Fibrillation: A Systematic Review and Meta-Analysis,” Journal of the American Heart Association 13, no. 17 (2024): e033059, https://doi.org/10.1161/JAHA.123.033059.
- 14N. F. Marrouche, O. Wazni, C. McGann, et al., “Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The DECAAF II Randomized Clinical Trial,” Journal of the American Medical Association 327, no. 23 (2022): 2296–2305, https://doi.org/10.1001/jama.2022.8831.
- 15G. Caixal, F. Alarcon, T. F. Althoff, et al., “Accuracy of Left Atrial Fibrosis Detection With Cardiac Magnetic Resonance: Correlation of Late Gadolinium Enhancement With Endocardial Voltage and Conduction Velocity,” Europace 23, no. 3 (2021): 380–388, https://doi.org/10.1093/europace/euaa313.
- 16S. Cao, Q. Zhou, J. L. Chen, B. Hu, and R. Q. Guo, “The Differences in Left Atrial Function Between Ischemic and Idiopathic Dilated Cardiomyopathy Patients: A Two-Dimensional Speckle Tracking Imaging Study,” Journal of Clinical Ultrasound 44, no. 7 (2016): 437–445, https://doi.org/10.1002/jcu.22352.
- 17A. D'Andrea, P. Caso, S. Romano, et al., “Association Between Left Atrial Myocardial Function and Exercise Capacity in Patients With Either Idiopathic or Ischemic Dilated Cardiomyopathy: A Two-Dimensional Speckle Strain Study,” International Journal of Cardiology 132, no. 3 (2009): 354–363, https://doi.org/10.1016/j.ijcard.2007.11.102.
- 18R. M. Inciardi, B. Claggett, M. Minamisawa, et al., “Association of Left Atrial Structure and Function with Heart Failure in Older Adults,” Journal of the American College of Cardiology 79, no. 16 (2022): 1549–1561, https://doi.org/10.1016/j.jacc.2022.01.053.
- 19M. Minamisawa, R. M. Inciardi, B. Claggett, et al., “Left Atrial Structure and Function of the Amyloidogenic V122I Transthyretin Variant in Elderly African Americans,” European Journal of Heart Failure 23, no. 8 (2021): 1290–1295, https://doi.org/10.1002/ejhf.2200.
- 20J. L. Januzzi, Jr., M. F. Prescott, J. Butler, et al., “Association of Change in N-Terminal Pro-B-Type Natriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment with Cardiac Structure and Function in Patients with Heart Failure with Reduced Ejection Fraction,” Journal of the American Medical Association 322, no. 11 (2019): 1085–1095, https://doi.org/10.1001/jama.2019.12821.
- 21R. M. Inciardi, B. Claggett, D. K. Gupta, et al., “Cardiac Structure and Function and Diabetes-Related Risk of Death or Heart Failure in Older Adults,” Journal of the American Heart Association 11, no. 6 (2022): e022308, https://doi.org/10.1161/JAHA.121.022308.
- 22A. S. Desai, S. D. Solomon, A. M. Shah, et al., “Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial,” Journal of the American Medical Association 322, no. 11 (2019): 1077–1084, https://doi.org/10.1001/jama.2019.12843.
- 23M. Kloosterman, M. Rienstra, B. A. Mulder, I. C. Van Gelder, and A. H. Maass, “Atrial Reverse Remodelling Is Associated With Outcome of Cardiac Resynchronization Therapy,” Europace 18, no. 8 (2016): 1211–1219, https://doi.org/10.1093/europace/euv382.
- 24C. Valzania, F. Gadler, G. Boriani, C. Rapezzi, and M. J. Eriksson, “Effect of Cardiac Resynchronization Therapy on Left Atrial Size and Function as Expressed by Speckle Tracking 2-Dimensional Strain,” American Journal of Cardiology 118, no. 2 (2016): 237–243, https://doi.org/10.1016/j.amjcard.2016.04.042.
- 25A. Brenyo, M. S. Link, A. Barsheshet, et al., “Cardiac Resynchronization Therapy Reduces Left Atrial Volume and the Risk of Atrial Tachyarrhythmias in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy),” Journal of the American College of Cardiology 58, no. 16 (2011): 1682–1689, https://doi.org/10.1016/j.jacc.2011.07.020.
- 26L. R. Hammersboen, M. Stugaard, A. Puvrez, et al., “Mechanism and Impact of Left Atrial Dyssynchrony on Long-Term Clinical Outcome during Cardiac Resynchronization Therapy,” JACC Cardiovasc Imaging (2024), https://doi.org/10.1016/j.jcmg.2024.09.008.
- 27X. Ma, Z. Chen, Y. Song, et al., “CMR Feature Tracking-Based Left Atrial Mechanics Predicts Response to Cardiac Resynchronization Therapy and Adverse Outcomes,” Heart Rhythm 21, no. 8 (2024): 1354–1362, https://doi.org/10.1016/j.hrthm.2024.03.028.
- 28M. St John Sutton, C. Linde, M. R. Gold, et al., “Left Ventricular Architecture, Long-Term Reverse Remodeling, and Clinical Outcome in Mild Heart Failure With Cardiac Resynchronization: Results from the REVERSE Trial,” JACC Heart Failure 5, no. 3 (2017): 169–178, https://doi.org/10.1016/j.jchf.2016.11.012.
- 29K. Negishi, T. Negishi, O. Zardkoohi, et al., “Left Atrial Booster Pump Function Is an Independent Predictor of Subsequent Life-Threatening Ventricular Arrhythmias in Non-Ischaemic Cardiomyopathy,” European Heart Journal - Cardiovascular Imaging 17, no. 10 (2016): 1153–1160, https://doi.org/10.1093/ehjci/jev333.
- 30M. Yazaki, T. Nabeta, T. Inomata, et al., “Clinical Significance of Left Atrial Geometry in Dilated Cardiomyopathy Patients: A Cardiovascular Magnetic Resonance Study,” Clinical Cardiology 44, no. 2 (2021): 222–229, https://doi.org/10.1002/clc.23529.
- 31M. M. Benjamin, M. S. Munir, and M. A. Syed, “Prognostic Value of Left Atrial Size and Function by Cardiac Magnetic Resonance in Non-Ischemic Cardiomyopathy,” International Journal of Cardiovascular Imaging 40, no. 10 (2024): 2041–2046, https://doi.org/10.1007/s10554-024-03196-7.
- 32A. Gulati, T. F. Ismail, A. Jabbour, et al., “Clinical Utility and Prognostic Value of Left Atrial Volume Assessment by Cardiovascular Magnetic Resonance in Non-Ischaemic Dilated Cardiomyopathy,” European Journal of Heart Failure 15, no. 6 (2013): 660–670, https://doi.org/10.1093/eurjhf/hft019.
- 33M. Merlo, D. Stolfo, M. Gobbo, et al., “Prognostic Impact of Short-Term Changes of E/E' ratio and Left Atrial Size in Dilated Cardiomyopathy,” European Journal of Heart Failure 21, no. 10 (2019): 1294–1296, https://doi.org/10.1002/ejhf.1543.
- 34A. Rossi, M. Cicoira, L. Zanolla, et al., “Determinants and Prognostic Value of Left Atrial Volume in Patients With Dilated Cardiomyopathy,” Journal of the American College of Cardiology 40, no. 8 (2002): 1425, https://doi.org/10.1016/s0735-1097(02)02305-7.
- 35M. Barki, M. Losito, M. M. Caracciolo, et al., “Left Atrial Strain in Acute Heart Failure: Clinical and Prognostic Insights,” European Heart Journal - Cardiovascular Imaging 25, no. 3 (2024): 315–324, https://doi.org/10.1093/ehjci/jead287.
- 36E. Carluccio, P. Biagioli, A. Mengoni, et al., “Left Atrial Reservoir Function and Outcome in Heart Failure With Reduced Ejection Fraction,” Circulation: Cardiovascular Imaging 11, no. 11 (2018): e007696, https://doi.org/10.1161/CIRCIMAGING.118.007696.
- 37A. G. Raafs, J. L. Vos, M. Henkens, et al., “Left Atrial Strain Has Superior Prognostic Value to Ventricular Function and Delayed-Enhancement in Dilated Cardiomyopathy,” JACC Cardiovasc Imaging 15, no. 6 (2022): 1015–1026, https://doi.org/10.1016/j.jcmg.2022.01.016.
- 38F. Fortuni, P. Biagioli, R. Myagmardorj, et al., “Left Atrioventricular Coupling Index: A Novel Diastolic Parameter to Refine Prognosis in Heart Failure,” Journal of the American Society of Echocardiography 37, no. 11 (2024): 1038–1046, https://doi.org/10.1016/j.echo.2024.06.013.
- 39F. Bandera, R. Martone, L. Chacko, et al., “Clinical Importance of Left Atrial Infiltration in Cardiac Transthyretin Amyloidosis,” JACC Cardiovasc Imaging 15, no. 1 (2022): 17–29, https://doi.org/10.1016/j.jcmg.2021.06.022.
- 40G. Vergaro, A. Aimo, C. Rapezzi, et al., “Atrial Amyloidosis: Mechanisms and Clinical Manifestations,” European Journal of Heart Failure 24, no. 11 (2022): 2019–2028, https://doi.org/10.1002/ejhf.2650.
- 41A. Ferkh, P. Geenty, L. Stefani, et al., “Diagnostic and Prognostic Value of the Left Atrial Myopathy Evaluation in Cardiac Amyloidosis Using Echocardiography,” ESC Heart Failure (2024): 4139–4147, https://doi.org/10.1002/ehf2.15013.
- 42J. C. Lyne, J. Petryka, and D. J. Pennell, “Atrial Enhancement by Cardiovascular Magnetic Resonance in Cardiac Amyloidosis,” European Heart Journal 29, no. 2 (2008): 212, https://doi.org/10.1093/eurheartj/ehm351.
- 43C. P. Leeson, S. G. Myerson, G. B. Walls, S. Neubauer, and O. J. Ormerod, “Atrial Pathology in Cardiac Amyloidosis: Evidence From ECG and Cardiovascular Magnetic Resonance,” European Heart Journal 27, no. 14 (2006): 1670, https://doi.org/10.1093/eurheartj/ehi766.
- 44G. Di Bella, F. Minutoli, A. Madaffari, et al., “Left Atrial Function in Cardiac Amyloidosis,” Journal of Cardiovascular Medicine (Hagerstown) 17, no. 2 (2016): 113–121, https://doi.org/10.2459/JCM.0000000000000188.
- 45F. Edbom, P. Lindqvist, U. Wiklund, et al., “Assessing Left Atrial Dysfunction in Cardiac Amyloidosis Using LA-LV Strain Slope,” European Heart Journal–Imaging Methods and Practice 2, no. 3 ( 2024): qyae100, https://doi.org/10.1093/ehjimp/qyae100.
- 46M. M. Benjamin, P. Arora, M. S. Munir, et al., “Association of Left Atrial Hemodynamics by Magnetic Resonance Imaging With Long-Term Outcomes in Patients with Cardiac Amyloidosis,” Journal of Magnetic Resonance Imaging 57, no. 4 (2023): 1275–1284, https://doi.org/10.1002/jmri.28320.
- 47K. Tigen, M. Sunbul, T. Karaahmet, et al., “Early Detection of Bi-Ventricular and Atrial Mechanical Dysfunction Using Two-Dimensional Speckle Tracking Echocardiography in Patients With Sarcoidosis,” Lung 193, no. 5 (2015): 669–675, https://doi.org/10.1007/s00408-015-9748-0.
- 48J. F. Viles-Gonzalez, L. Pastori, A. Fischer, J. P. Wisnivesky, M. G. Goldman, and D. Mehta, “Supraventricular Arrhythmias in Patients With Cardiac Sarcoidosis Prevalence, Predictors, and Clinical Implications,” Chest 143, no. 4 (2013): 1085–1090, https://doi.org/10.1378/chest.11-3214.
- 49M. A. Cain, M. D. Metzl, A. R. Patel, et al., “Cardiac Sarcoidosis Detected by Late Gadolinium Enhancement and Prevalence of Atrial Arrhythmias,” American Journal of Cardiology 113, no. 9 (2014): 1556–1560, https://doi.org/10.1016/j.amjcard.2014.01.434.
- 50K. Yodogawa, Y. Fukushima, T. Ando, et al., “Prevalence of Atrial FDG Uptake and Association With Atrial Arrhythmias in Patients With Cardiac Sarcoidosis,” International Journal of Cardiology 313 ( 2020): 55–59, https://doi.org/10.1016/j.ijcard.2020.04.041.
- 51S. Eshoo, C. Semsarian, D. L. Ross, T. H. Marwick, and L. Thomas, “Comparison of Left Atrial Phasic Function in Hypertrophic Cardiomyopathy Versus Systemic Hypertension Using Strain Rate Imaging,” American Journal of Cardiology 107, no. 2 (2011): 290–296, https://doi.org/10.1016/j.amjcard.2010.08.071.
- 52M. M. Benjamin, M. Khalil, M. S. Munir, M. Kinno, and M. A. Syed, “Association of Left Atrial Size and Function by Cardiac Magnetic Resonance Imaging With Long Term Outcomes in Patients With Hypertrophic Cardiomyopathy,” International Journal of Cardiovascular Imaging 39, no. 6 (2023): 1181–1188, https://doi.org/10.1007/s10554-023-02814-0.
- 53Y. Yang, G. Yin, Y. Jiang, L. Song, S. Zhao, and M. Lu, “Quantification of Left Atrial Function in Patients With Non-Obstructive Hypertrophic Cardiomyopathy by Cardiovascular Magnetic Resonance Feature Tracking Imaging: A Feasibility and Reproducibility Study,” Journal of Cardiovascular Magnetic Resonance 22, no. 1 (2020): 1, https://doi.org/10.1186/s12968-019-0589-5.
- 54A. Hajj-Ali, A. Gaballa, E. Akintoye, et al., “Long-Term Outcomes of Patients With Apical Hypertrophic Cardiomyopathy Utilizing a New Risk Score,” JACC: Advances 3, no. 10 (2024): 101235, https://doi.org/10.1016/j.jacadv.2024.101235.
- 55Y. Tang, X. Ma, J. Wang, et al., “Incremental Prognostic Value of Left Atrial Strain in Apical Hypertrophic Cardiomyopathy: A Cardiovascular Magnetic Resonance Study,” European Radiology (2024): IN PRESS, https://doi.org/10.1007/s00330-024-11058-y.
- 56M. von Roeder, K. P. Rommel, J. T. Kowallick, et al., “Response by von Roeder Et al. to Letter Regarding Article, “Influence of Left Atrial Function on Exercise Capacity and Left Ventricular Function in Patients with Heart Failure and Preserved Ejection Fraction”,” Circulation: Cardiovascular Imaging 10, no. 8 (2017): e005467, https://doi.org/10.1161/CIRCIMAGING.117.006785.
- 57M. C. Meucci, F. Fortuni, X. Galloo, et al., “Left Atrioventricular Coupling Index in Hypertrophic Cardiomyopathy and Risk of New-Onset Atrial Fibrillation,” International Journal of Cardiology 363 (2022): 87–93, https://doi.org/10.1016/j.ijcard.2022.06.017.
- 58P. Debonnaire, E. Joyce, Y. Hiemstra, et al., “Left Atrial Size and Function in Hypertrophic Cardiomyopathy Patients and Risk of New-Onset Atrial Fibrillation,” Circulation: Arrhythmia and Electrophysiology 10, no. 2 (2017): e004052, https://doi.org/10.1161/CIRCEP.116.004052.
- 59L. K. Williams, R. H. Chan, S. Carasso, et al., “Effect of Left Ventricular Outflow Tract Obstruction on Left Atrial Mechanics in Hypertrophic Cardiomyopathy,” BioMed Research International 2015 (2015): 481245, https://doi.org/10.1155/2015/481245.
- 60S. F. Nagueh, N. M. Lakkis, K. J. Middleton, et al., “Changes in Left Ventricular Filling and Left Atrial Function Six Months After Nonsurgical Septal Reduction Therapy for Hypertrophic Obstructive Cardiomyopathy,” Journal of the American College of Cardiology 34, no. 4 (1999): 1123–1128, https://doi.org/10.1016/s0735-1097(99)00341-1.
- 61M. G. Rabbat, R. Y. Kwong, J. F. Heitner, et al., “The Future of Cardiac Magnetic Resonance Clinical Trials,” JACC Cardiovasc Imaging 15, no. 12 (2022): 2127–2138, https://doi.org/10.1016/j.jcmg.2021.07.029.