This was a single-center, retrospective analysis of patients with AF who had impaired LV function (LVEF <50%) on the initial or worst echocardiogram before ablation and who underwent catheter ablation for the AF at Saiseikai Yokohamashi Tobu Hospital from June 2016 to January 2020. We excluded patients receiving hemodialysis or who had structural heart disease and suspicion of other cardiomyopathies by echocardiography. After control of the AF, the patients were divided into two groups based on whether the LVEF was <60% (Group 1) or ≧60% (Group 2) more than 3 months after ablation. If the patient’s LVEF became ≧60% within 3 months after ablation, the patient was included in Group 2. We compared the baseline characteristics between the two groups. This study was conducted at Saiseikai Yokohamashi Tobu Hospital and was approved by the institutional review board of Saiseikai Yokohamashi Tobu Hospital (IRB # 20200050).
2.2 Echocardiographic data
Echocardiography was performed using various devices (Vivid E95, GE Healthcare Japan Corp.; APLIO Artida, APLIO I900, and APLIO 300, Canon Medical Systems Corp.; and iE, Philips Japan, Ltd.). LVEF and LAV were measured by the modified Simpson’s method and by the prolate-ellipsoid method (LAV-echo), respectively. Division of the LAV-echo by the BSA resulted in LAV index of echocardiography (LAVI-echo). If LVEF became ≧60% within 3 months after ablation, the data were adopted. If the patient had a recurrence after ablation, echocardiography was performed over 3 months after the arrhythmia resolved.
2.3 CT data
We performed CT before ablation. We utilized the CT data, and the anatomy of LA and PVs was constructed by Ziostation2 Version 2.9.7.1 (Ziosoft, Inc). Vertical and horizontal rotation was performed to maximize the length between the PV roof and the first bifurcation of PV. The LA‐PV junction was determined as previously reported6,7,8. The LA-LAA junction was defined as the root of LAA. LAV determined by CT (LAV-CT) was removed of the LAA and PVs by a manual procedure at these junctions (Figure 1). Division of the LAV by the BSA resulted in the LAV index of CT (LAVI-CT).
2.4 Ablation procedure
Patients received intravenous heparin with a target minimum activated clotting time of 300 seconds. AF ablation was performed using a cryoballoon (Arctic Front Advance; Medtronic, Inc) for PVI and a 3-dimentional electroanatomic mapping system (EnSite Precision; Abbott, Inc) in all patients. If the PVI was incomplete, complete PVI was performed with an irrigated radiofrequency catheter (FlexAbility; Abbott, Inc). Cavotricuspid isthmus line ablation was completed with the radiofrequency catheter.
2.5 Post-ablation follow-up
A 12-lead electrocardiogram was performed at every visit. 24-hour Holter monitoring and echocardiography were performed according to the physician’s judgment. If patients had a CIED, AF was monitored. Biopsy and CMR imaging were not performed. Recurrence of AF is defined as longer than 30 seconds of AF or atrial tachycardia/flutter episode more than 3 months after ablation.
2.6 Statistical analysis
Continuous data were described as median and interquartile range and categorical data as numbers and percentages. The Mann–Whitney U test and Fisher exact test were used to compare differences across groups. All tests were 2 sided, and a p value < 0.05 was considered to indicate statistical significance. A ROC curve was calculated to identify the optimal cutoff point where sensitivity and specificity would be maximal for the prediction of improved LVEF. The AUC and its 95% CI were calculated as measures of the accuracy of the data. Statistical analysis was performed using IBM SPSS Advanced Statistics 24 (IBM, Inc). We could not perform multivariable analysis because of the small amount of data.
3 Results
3.1 Characteristics of 2 groups at baseline and predictors for improving LVEF
A total of 31 patients (nine in Group1 and 22 in Group 2) were included in this study. One patient in Group 1 and eight patients in Group 2 had AF controlled by cardioversion and/or medications before ablation. In Group 1, one patient had a CIED before ablation and two patients had it after ablation. In Group 2, nobody had CIED. LAV-CT, LAVI-CT, LAVI-echo, and LAD were significant between the groups. Small LAV-CT, LAVI-CT, LAV-echo, and LAD were predictors for improving LVEF. All other characteristics were not significantly different between the groups (Table 1). The AUCs of LAV-CT, LAVI-CT, LVAI-echo, and LAD were 0.859 (95% CI 0.729-0.991, p=0.002), 0.869 (95% CI 0.741-0.997, p=0.001), 0.798 (95% CI 0.640-0.956, p=0.010), and 0.750 (95% CI 0.545-0.955, p=0.031), respectively. The cutoff values were 147 ml, 79 ml/m2, 37 ml/mm2, and 45.8 mm, respectively (Figure 2).
3.2 Characteristics of 2 groups after ablation
Post-ablation echocardiographic data were not significantly different between the groups except for the follow up period of echocardiography and LAD. Recurrence of arrhythmia was not significantly different between the groups (Table 2).
4 Discussion
4.1 Major finding
Several pieces of previous literature reported that small LV dimensions, younger age, and male sex may help to differentiate TCM from DCM3,4,9,10. These parameters in this study were not significantly different between the two groups. LAV-CT, LAVI-CT, LAVI-echo, and LAD were significantly different, whereas the difference in the LAV-echo was close to significant (p = 0.0583). LA dilation is frequently observed in DCM because of diastolic dysfunction, functional mitral regurgitation, AF, and LV cavity enlargement11. Therefore, small LA volume and dimension may be predictors of TCM with AF. Small LAV-echo and LAD (LAV-echo <67 ml and LAD <45.8 mm, which were the optimal cutoff values) may be helpful for the diagnosis of TCM with AF, because echocardiography is noninvasive and easy. However, these results of this study may not apply to TCM with other arrhythmias.
4.2 AF ablation
AF is the most prevalent arrhythmia and the most common cause of TCM1,2, but there is no clear data on the prevalence of TCM12. TCM in 4% of patients referred for PVI was reported13. Ventricular rate during AF does not predict for LVEF improvement14. Thus, it is difficult the diagnosis of TCM with AF. In case of other supraventricular arrhythmias, we can recognize that they cause TCM and we can recommend ablation3,15,16,17. All patients with HF and AF should have ablation for AF18,19, but it is prevented by the risk of the procedure’s complications20,21,22,23: Phrenic nerve injury, PV stenosis, Atrioesophageal fistula, and so on. Hence, we recognize some characteristics of TCM before ablation, and we are willing to recommend patients with possible TCM for ablation.
4.3 Variety in Group 1
Patients in Group 1 were classified into two groups. In Group A, their LVEF improved a little. In group B, their LVEF remained the same or decreased. Group A was composed of the following patients: (1) those whose LVEF had been improving, (2) those with overlapping DCM and TCM1, and (3) those with recurrence of AF. Group B was composed of just DCM or other cardiomyopathies. Accordingly, we should have followed Group 1 longer.
4.4 Limitations
This study has several limitations. It was a single-center study and included a small number of patients. LAV-CT was measured by hand and it might not be exact. Some tests, such as echocardiography, were performed according to individual judgment. Although three patients (33%) in Group 1 had CIED in the end, we did not notice the occult recurrence of AF.
5 Conclusion
LAV-CT <147 ml, LAVI-CT <79 ml/m2, LAVI- echo <37 ml/m2, and LAD <45.8 mm were predictors of LVEF improvement. The parameters measured by CT were more useful than by echocardiography. Small LAV and dimension before ablation may be predictors for TCM with AF and may be helpful for its diagnosis.
Conflict of interests
The authors declare that there are no conflicts of interests.
References
  1. Gopinathannair R, Etheridge SP, Marchlinski FE, Spinale FG, Lakkireddy D, Olshansky B. Arrhythmia-induced cardiomyopathy: Mechanisms, recognition and management. J Am Coll Cardiol 2015;66:1714-1728.
  2. Nerheim P, Birger-Botkin S, Piracha L, Olshansky B. Heart failure and sudden death in patients with tachycardia-induced cardiomyopathy and recurrent tachycardia. Circulation 2004;110:247-252.
  3. Medi C, Kalman JM, Haqqani H, Vohra JK, Morton JB, Sparks PB, Kistler PM. Tachycardia-mediated cardiomyopathy secondary to focal atrial tachycardia: long-term outcome after catheter ablation. J Am Coll Cardiol 2009;53:1791-1797.
  4. Lishmanov A, Chockalingam P, Senthilkumar A, Chockalingam A. Tachycardia-induced cardiomyopathy: evaluation and therapeutic options. Congest Heart Fail 2010;16:122-126.
  5. Hasdemir C, Yuksel A, Camli D, Kartal Y, Simsek E, Musayev O, Isayev E, Aydin M, Can LH. Late gadolinium enhancement CMR in patients with tachycardia-induced cardiomyopathy caused by idiopathic ventricular arrhythmia. Pacing Clin Electrophysiol 2012;35:465-470.
  6. Shah DC, Haïssaguerre M, Jaïs P, Hocini M, Yamane T, Deisenhofer I, Garrigue S, Clémenty J. Curative catheter ablation of paroxysmal atrial fibrillation in 200 patients: strategy for presentations ranging from sustained atrial fibrillation to no arrhythmias. Pacing Clin Electrophysiol 2001; 4:1541-1558.
  7. Shah DC.Evaluating pulmonary vein isolation. J Arrhythmia 2008;24:180-194.
  8. Manghat NE, Mathias HC, Kakani N, Hamilton MC, Morgan-Hughes G, Roobottom CA. Pulmonary venous evaluation using electrocardiogram-gated 64-detector row cardiac CT.  Br J Radiol 2012;85:965-971.
  9. Jeong YH, Choi KJ, Song JM, Hwang ES, Park KM, Nam GB, Kim JJ, Kim YH. Diagnostic approach and treatment strategy in tachycardia-induced cardiomyopathy. Clin Cardiol 2008;31:172-178.
  10. Ju W, Yang B, Li M, Zhang F, Chen H, Gu K, Yu J, Cao K, Chen M. Tachycardiomyopathy complicated by focal atrial tachycardia: incidence, risk factors, and long-term outcome. J Cardiovasc Electrophysiol 2014;25:953-957.
  11. Japp AG, Gulati A, Cook SA, Cowie MR, Prasad SK. The diagnosis and evaluation of dilated cardiomyopathy. J Am Coll Cardiol 2016;67:2996-3010.
  12. Huizar JF, Ellenbogen AK, Tan AY, Kaszala K. Arrhythmia-induced cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol 2019;73:2328-2344.
  13. Gentlesk PJ, Sauer WH, Gerstenfeld EP, Lin D, Dixit S, Zado E, Callans D, Marchlinski FE. Reversal of left ventricular dysfunction following ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2007;18:9-14.
  14. Redfield MM, Kay GN, Jenkins LS, Mianulli M, Jensen DN, Ellenbogen KA. Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation. Mayo Clin Proc 2000;75:790-795.
  15. Luchsinger JA, Steinberg JS. Resolution of cardiomyopathy after ablation of atrial flutter. J Am Coll Cardiol 1998;32:205–210.
  16. Han FT, Riles EM, Badhwar N, Scheinman MM. Clinical features and sites of ablation for patients with incessant supraventricular tachycardia from concealed nodofascicular and nodoventricular tachycardias. JACC Clin Electrophysiol 2017;3:1547–1556.
  17. Bensler JM, Frank CM, Razavi M, Rasekh A, Saeed M, Haas PC, Nazeri A, Massumi A. Tachycardia-mediated cardiomyopathy and the permanent form of junctional reciprocating tachycardia. Tex Heart Inst J 2010;37:695–698.
  18. Marrouche NF, Brachmann J, Andresen D, Siebels J, Boersma L, Jordaens L, Merkely B, Pokushalov E, Sanders P, Proff J, Schunkert H, Christ H, Vogt J, Bänsch D. Catheter ablation for atrial fibrillation with heart Failure. N Engl J Med 2018;378:417-427.
  19. Prabhu S, Taylor AJ, B.T. Costello BT, Kaye DM, McLeiian AJA, Voskoboinik A, Sugumar H, Lockwood SM, Stokes MB, Pathik B, Nalliah CJ, Wong QR, Azzopardi SM, Gutman SJ, Lee G, Layland J, Mariani JA, Ling LH, Kalman JM, Kistler PM. Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study. J Am Coll Cardiol 2017;70:1949-1961.
  20. Kuck KH, Brugada J, Fürnkranz A, Metzer A, Ouyang F, Chun KRJ, Elvan A, Arentz T, Bestehorn K, Pocock SJ, Albenque JP, Tondo C, FIRE AND ICE Investigators. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med 2016;374: 2235–2245.
  21. Okumura K, Matsumoto K, Kobayashi Y, Nogami A, Hokanson RB, Kueffer F, CRYO-Japan PMS Study Investigators. Safety and efficacy of cryoballoon ablation for paroxysmal atrial fibrillation in Japan - Results from the Japanese prospective post-market surveillance study. Circ J 2016;80:1744–1749.
  22. Narui R, Tokuda M, Matsushima M, Isogai R, Tokutake K, Yokoyama K, Hioki M, Ito K, Tanigawa S, Yamashita S, Inada K, Shibayama K, Matsuo S, Miyanaga S, Sugimoto K, Yoshimura M, Yamane T. Incidence and factors associated with the occurrence of pulmonary vein narrowing after cryoballoon ablation. Circ Arrhythm Electrophysiol 2017;10:e004588.
  23. Kawasaki R, Gauri A, Elmouchi D, Duggal M, Bhan A. Atrioesophageal fistula complicating cryoballoon pulmonary vein isolation for paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 2014;25:787–792.