This is a single-center retrospective study. This study consecutively enrolled myocarditis patients confirmed by endomyocardial biopsy (EMB) who underwent CA for sustained VT at the Fuwai Hospital, Chinese Academy of Medical Sciences from February 2017 to March 2023. Patients with IHD undergoing CA for sustained VT during the same period were included for comparison. Clinical presentations, family history, comorbidities, 12-lead electrocardiogram (ECG) results, and EMB of all patients were obtained from the electronic medical record system.

Sustained VT was defined as either lasting more than 30 seconds or necessitating termination within 30 seconds due to hemodynamic compromise [15]. The diagnosis of myocarditis was based on the pathological criteria of the current guideline [16]. EMB was performed via the right femoral vein to obtain myocardial tissue from the right ventricular septum. Myocarditis was pathologically diagnosed and staged according to the Dallas criteria [17]. In general, acute myocarditis showed myocardial cell necrosis and inflammation activation, while chronic myocarditis involved both destruction and remodeling. For patients with myocarditis, EMB was performed concurrently with CA using Jawz 2.2 mm Forceps, Maxi-Curved, 105 cm (Argon Medical Devices, Frisco, TX, USA). IHD was a cardiovascular condition characterized by diminished myocardial blood flow resulting from coronary artery disease [18].

Prior to the ablation procedure, all patients provided informed consent and were prepared following the standard clinical protocol of our department. Mapping and CA procedures were carried out under local anesthesia and sedation. ECG monitoring was conducted continuously throughout the procedure. A decapolar steerable electrode catheter was introduced into the coronary sinus through femoral venous access, while a standard fixed-curve quadripolar catheter was positioned in the right ventricle. Ventricular programmed or incremental stimulation was used to induce clinical VT until the ventricular refractory period was reached or VT onset occurred. For inducible and tolerable VTs, activation mapping and entrainment mapping were performed to identify critical isthmuses of reentry; for uninducible or unstable VTs, substrate mapping under sinus rhythm were performed. Electroanatomic mapping was conducted using either the CARTO 3D electroanatomical mapping system (Biosense Webster, Diamond Bar, CA, USA) or the Ensite Precision 3D electroanatomical mapping system (Abbott Laboratories, St. Paul, MN, USA). Endocardial mapping-guided ablation was performed in all patients. For those in whom endocardial ablation failed, epicardial mapping via subxiphoid pericardial puncture was considered. The arrhythmogenic substrates comprised split electrograms, low voltage ($\le$0.5 mV), or fractionated electrograms, which were characterized by multiple potentials with $\ge$2 distinct components, $>$20 ms of isoelectric segments between the peaks of these components, and either a long duration ($>$80 ms) or late potentials.

Ablation was conducted with radiofrequency energy, set at a target temperature of 45 °C and a maximum power of 50 W, utilizing irrigation at a flow rate of 12–30 cc/min. The ablation catheters used for catheter ablation were the Flexibility^TM ablation catheter (Abbott Laboratories, St. Paul, MN, USA) or the THERMOCOOL SMARTTOUCH ablation catheter (Biosense Webster, Diamond Bar, CA, USA). For ablations guided by activation mapping, the effectiveness of the ablation is evaluated post-procedure by repeating ventricular stimulation. If no VT can be induced, the ablation is defined as successful. If clinical VT cannot be induced, but other VT morphologies are inducible, the ablation is considered partially successful. If clinical VT is still inducible, the ablation is deemed a failure. For ablation guided by substrate mapping, the procedure target was eliminating all arrhythmogenic substrates.

Patients were followed up through phone calls or clinic visits at 3, 6, and 12 months after discharge, and then annually thereafter. Regular telephone interviews were conducted with patients or their family members as well. At each follow-up, patients underwent 12-lead ECG and 24-hour Holter monitoring to identify arrhythmias. For those with an implantable cardioverter-defibrillator (ICD), device checks were performed every 6 months. The primary endpoint of this study was recurrent VT. VT recurrence was defined as sustained VT (duration $>$30 s), documented by ECG or Holter monitoring, or appropriate ICD shocks. During the follow-up period, occurrences such as all-cause mortality, repeat CA for VT and ICD implantation would also be documented. Every effort was made to ascertain the causes of death for the patients.

The normality of the data was assessed using the Kolmogorov–Smirnov test. Continuous variables were expressed as means $\pm$ standard deviations or as medians with interquartile ranges (25th–75th percentiles), depending on the data distribution. Comparisons were performed using the t-test for normally distributed data and the Mann–Whitney U test for non-normally distributed data. Categorical variables were presented as counts and percentages, and comparisons were made using the $\chi$² test or Fisher’s exact test. To enhance credibility, propensity score matching (PSM) was employed to reduce potential confounders and selection bias in this retrospective study. Propensity scores were computed based on the characteristics outlined in Table 1. One-to-two nearest-neighbor matching was performed using a 0.25 caliper. After matching, a total of 32 patients were obtained. Standardized mean differences (SMD) were used to assess the differences between the matched groups, with a maximum SMD of 0.1 or even 0.15 was typically considered acceptable.

Event-free survival was assessed using the Kaplan–Meier method and analyzed with the log-rank test. Cox proportional hazard modeling was then performed, incorporating potential confounders identified from significant univariate associations (p 0.05). Multivariable Cox regression analysis was conducted to determine significant predictors of VT recurrence, accounting for relevant clinical covariates. Statistical analyses were performed using R software version 4.1.0 (R Foundation for Statistical Computing, Vienna, Austria). All tests were two-tailed, with statistical significance defined as p 0.05.

During the study period, 109 IHD patients and 20 myocarditis patients with proven EMB were enrolled (Fig. 1). The mean age was 57 $\pm$ 12 years old and the mean left ventricular ejection fraction (LVEF) was 48 $\pm$ 11%. 114 (88.4%) patients were male. 115 (89.1%) patients had a history of requiring termination of VT episodes due to compromised hemodynamics. In this population, the comorbidities ranked from high to low were hypertension (49.6%), diabetes (22.5%), and chronic kidney disease (6.2%). 73 (56.6%) patients had a history of smoking and 46 (35.7%) had a history of drinking. In addition, 34 (26.4%) patients had a history of ICD implantation and 17 (13.2%) had a history of CA. The baseline characteristics of the patient population are summarized in Table 1. Compared to IHD patients enrolled, patients with myocarditis have a significantly higher proportion of females, younger age, fewer comorbidities of hypertension, diabetes, smoking, and better LVEF (Table 1). After matching, no statistical differences were found between the 2 groups in all covariates (Table 1). In the myocarditis cohort, 15 (75.0%) patients were in the chronic stage while 5 (25.0%) patients were in the acute stage based on the results of the pathology report. All patients with myocarditis exhibited resistance to anti-arrhythmic drug therapy. There was no significant difference in the history of requiring termination of VT episodes due to compromised hemodynamics between acute and chronic myocarditis. In addition, 4 patients had giant cell myocarditis, 9 patients had lymphocytic myocarditis, 6 patients had atypical myocarditis, and 1 patient had cardiac sarcoidosis-related myocarditis. 10 patients received immunosuppressive therapy combined with steroid treatment, 3 patients received steroid treatment and the remaining 7 patients refused to undergo steroid or immunosuppressive therapy.

Fig. 1.

Study flowchart. AF, atrial fibrillation; CA, catheter ablation; EMB, endomyocardial biopsy; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease; VT, ventricular tachycardia.

In this study, activation mapping was performed in 21 (16.3 %) patients and substrate mapping was performed in 100 (77.5%) patients. 8 (6.2%) patients underwent epicardial mapping due to failed endocardial ablation. During the procedures, 20 (15.5%) patients experienced hemodynamically unstable VT requiring defibrillation. Table 2 presented the electrophysiological findings and the specific origin of VT was in Supplementary Table 1. Out of the 129 patients, 105 (81.4%) achieved complete success with CA, 20 (15.5%) experienced partial success, and 4 (3.1%) encountered failure. 121 (93.8%) patients underwent endocardial CA and 8 (6.2%) patients underwent epicardial CA. Figs. 2,3 show the cardiac electrophysiological findings of a patient with myocarditis and a patient with IHD, respectively. In terms of CA complications, 3 patients developed pericardial effusion, with 1 requiring pericardial drainage. During hospitalization, 13 (10.1%) patients underwent ICD implantation following CA. Patients declined ICD implantation primarily because of economic concerns, but also out of fear of potential complications.

Fig. 2.

Sustained ventricular tachycardia in a patient with myocarditis. (A) The endomyocardial biopsy finding. Scale bar: 20 µm. (B) The electrocardiogram of sustained ventricular tachycardia. (C) Left ventricular endocardial substrate mapping results. (D) Activation mapping results and failure of ventricular tachycardia ablation. (E) Left ventricular epicardial substrate mapping results. (F) Activation mapping results and success of ventricular tachycardia ablation. ABL, ablation; CL, cycle length; LAT, local activation time; ECG, electrocardiogram; CS, coronary sinus.

Fig. 3.

Sustained ventricular tachycardia in a patient with ischemic heart disease. (A) The electrocardiogram of sustained ventricular tachycardia. (B) The endocardial substrate mapping results. (C) The epicardial substrate mapping results. (D) Successful ablation based on epicardial delayed potentials. ABL, ablation; ECG, electrocardiogram; REF, reference electrode; CS, coronary sinus.

Patients with myocarditis more commonly underwent activation mapping and less frequently undergo substrate mapping, compared with IHD patients (Table 2). Of note, myocarditis patients had a significantly lower rate of complete success than IHD patients [12 (60.0%) vs. 93 (85.3%), p = 0.013] (Table 2). However, the CA failure rates of the two groups of patients did not show a statistically significant difference. There was no notable contrast in terms of CA complications and ICD implantation when comparing patients with IHD to those with myocarditis (all p $>$ 0.05). The CA outcomes of the matched cohorts were consistent with the results described above (Table 3). In the myocarditis cohort, the overall complete success rate of CA during the acute myocarditis was 40.0%, which appeared to be lower than that observed in the chronic stage (66.7%), although this difference did not reach statistical significance (p = 0.347). The complete success rate of CA in patients with chronic myocarditis are comparable to that in IHD patients [10 (66.7%) vs. 93 (85.3%), p = 0.132] and was significantly lower in acute myocarditis patients than that in IHD patients [2 (40.0%) vs. 93 (85.3%), p = 0.032]. One patient in each of the acute myocarditis subgroup and chronic myocarditis subgroup developed pericardial effusion after CA, with no statistical difference observed. One patient in the acute myocarditis subgroup underwent ICD implantation following CA.

In a follow-up with an average duration of 37 $\pm$ 21 months, 65 (50.3%) patients experienced a recurrence of VT, 21 (16.3%) underwent ICD discharge, 16 (12.4%) patients underwent a second CA for VT recurrence, 8 (6.2%) patients received an ICD and 11 (8.5%) patients died. Among them, 9 (7.0%) patients died from cardiovascular causes. In the myocarditis cohort, 8 (40.0%) patients experienced a recurrence of VT, 2 (10.0%) patients underwent a second CA, and 2 (10.0%) died (Table 3). In addition, no patient underwent ICD implantation or experienced anti-tachycardia pacing during follow up in the myocarditis cohort (Table 3). In the IHD cohort, 57 (52.3%) patients experienced a recurrence of VT, 14 (12.8%) patients underwent a second CA for VT recurrence, and 9 (8.3%) died (Table 3). The one-year and two-year estimated rates of VT recurrence freedom in the myocarditis cohort were 64.0% (95% CI: 45.8%–98.4%) and 56.0% (95% CI: 36.6%–85.7%), respectively. The estimated freedom from death in the myocarditis cohort at one and two years was 89.1% (95% CI: 75.8%–100%) for both times. There was no statistically significant difference between the two groups in the aforementioned outcome events (Fig. 4). Similar follow up outcomes were also identified within the matched cohorts (Fig. 4). 93 patients had transthoracic echocardiography data during the follow-up period and the last LVEF was 47 $\pm$ 11%. There was no statistically significant difference between the final LVEF and the baseline LVEF (48 $\pm$ 11% vs. 47 $\pm$ 11%, p = 0.138) and similar conclusion was also found in the myocarditis subgroup and the IHD subgroup (both p $>$ 0.05). Multivariable Cox regression analysis indicated that being male and having a longer VT cycle length were protective factors for VT recurrence, while a history of ICD implantation was identified as a risk factor (Table 4).

Fig. 4.

Comparison of follow-up outcomes after catheter ablation for IHD and myocarditis. (A) Comparison of recurrence of VT after catheter ablation in IHD and myocarditis among all patients. (B) Comparison of recurrence of VT after catheter ablation in IHD and myocarditis in the PSM cohort. (C) Comparison of death after catheter ablation in IHD and myocarditis among all patients. (D) Comparison of death after catheter ablation in IHD and myocarditis in PSM cohort. IHD, ischemic heart disease; VT, ventricular tachycardia; PSM, propensity score matching.

In the myocarditis cohort, 1 patient in each of the acute phase subgroup and chronic phase subgroup suffered death, with no statistical difference observed (p = 0.335). In the chronic myocarditis, 5 patients (33.3%) experienced VT recurrence compared to 60.0% VT recurrence in the acute myocarditis, although without statistical significance (p = 0.165). In addition, the recurrence rates of VT in acute myocarditis and chronic myocarditis showed no statistically significant difference compared to IHD (both p $>$ 0.05). Furthermore, a single patient in the acute myocarditis underwent a second CA for VT recurrence during follow-up, while 1 chronic myocarditis patients underwent a second CA, with no statistically significant difference observed (p = 0.369). Of note, there was no significant difference in VT recurrence, a second CA for VT recurrence and death between patients receiving myocarditis treatment and patients not receiving (all p $>$ 0.05).