Abstract
Aims
We aimed to evaluate the effects of radiofrequency catheter ablation (RFCA) and the factors influencing mortality after RFCA in patients with pulmonary hypertension (PH) and atrial flutter (AFL).
Methods and results
Fifty‐eight consecutive PH patients with AFL who underwent an electrophysiological study and RFCA between April 2013 and August 2021 were selected for this study. In the study population, pulmonary arterial hypertension associated with congenital heart disease (PAH‐CHD) was the most common type of PH (n = 34, 59%), followed by idiopathic pulmonary arterial hypertension (IPAH) (n = 19, 33%). Typical atrial flutter was the most common type of atrial flutter (n = 50, 86.2%). Sinus rhythm was restored in 53 (91.4%) patients during RFCA. After a mean follow‐up of 33.8 months, AFL recurred in a total of 22 patients. Nine of them underwent repeat RFCA, and the site of the repeat ablation was not exactly the same as the first. At a median follow‐up of 34.6 months after the last ablation, none of the patients who underwent repeat RFCA experienced AFL recurrence, and all of these patients survived. There were no procedure‐related complications during hospitalization or follow‐up. Univariate Cox regression analysis suggested that AFL recurrence after the last ablation was not associated with all‐cause mortality. NT‐proBNP (HR: 1.00024, 95% CI: 1.00008–1.00041, P = 0.004), pulmonary artery systolic pressure (PASP) (HR: 1.048, 95% CI: 1.020–1.076, P = 0.001), and IPAH (vs. PAH‐CHD, HR: 7.720, 95% CI: 1.437–41.483, P = 0.017) were independent predictors of all‐cause mortality in PH patients with AFL after RFCA. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) of PASP for predicting all‐cause mortality was 0.708. There was no significant difference in the Kaplan–Meier curves for all‐cause mortality between patients with AFL recurrence after the last ablation and those without recurrence (P = 0.851). Patients with higher PASP (≥110 mmHg) and IPAH showed the lower survival rate in Kaplan–Meier curves.
Conclusion
Repeat ablation was safe and feasible in patients with recurrent AFL and can maintain sinus rhythm. AFL recurrence was not associated with all‐cause mortality, and patients with high PASP or IPAH were at higher risk for adverse outcomes.
Keywords: Atrial flutter, Pulmonary hypertension, Radiofrequency catheter ablation
Introduction
Pulmonary hypertension (PH) is a disease characterized by pulmonary arteriolar remodelling and increased pulmonary vascular resistance (PVR). As pulmonary vascular remodelling progresses, the right heart afterload gradually increases, and right heart remodelling gradually progresses until death from right heart failure. As PH research has deepened, the use of targeted drugs has greatly improved the quality of life and survival of patients. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) belong to Group 1 and Group 4 PH, respectively, which are the two main types of pulmonary hypertension and the main approved directions for targeted drug treatment. 1
In addition to general measures, medical therapy, interventional therapy, mechanical circulatory support, and lung transplantation, the diagnosis and treatment of pulmonary hypertension complications, including arrhythmias, haemoptysis, and mechanical complications, are also important in the process of disease management. Arrhythmias were one of the most common complications in PH patients, with supraventricular arrhythmias being the most common, mainly atrial flutter (AFL) and atrial fibrillation (AF). In the retrospective study of patients with PH, the incidence of AFL in PAH and CTEPH patients ranged from 3.8% to 5.4%. Other common complications of PAH and their incidence were haemoptysis (6%) and pulmonary artery aneurysm (38%). 2 , 3 Considering the small population base of PH patients and the low incidence of arrhythmias in PH patients, the total number of PH patients with AFL is small. Age and right heart size were associated with the occurrence of supraventricular arrhythmias. 4 , 5 Progressively elevated PVR leads to increased afterload, dilation, fibrosis, and mechanical remodelling of the right atrium and ventricle, resulting in electrical remodelling and atrial arrhythmias. 6 New‐onset arrhythmias are associated with clinical deterioration and mortality in patients with PAH. Treatment of patients with AFL consists mainly of antiarrhythmic drugs, electrical cardioversion and radiofrequency catheter ablation (RFCA), of which RFCA is recommended as the preferred option due to its high safety and efficacy, although there are more technical challenges than in patients with normal heart structure. 7 , 8 , 9 In a comparative registry study of PAH and CTEPH patients with AFL/AF, direct current cardioversion (DCCV) and antiarrhythmic drugs were shown to be more effective than heart rate control in maintaining sinus rhythm, which improved cardiac functional class and reduced mortality. 10 There is a lack of data reporting the use of amiodarone in PH patients with AFL, and there are no studies comparing the efficacy and safety of RFCA with amiodarone. Typical AFL was diagnosed in 86% of PH patients who underwent electrophysiological study for AFL, which was higher than the proportion diagnosed by electrocardiogram. Acute success was achieved in 86% of RFCA procedures. RFCA was able to reduce pulmonary artery systolic pressure and BNP, and 50% of these patients were free of AFL at 1 year. 11 Antiarrhythmic drugs and the numbers of hospitalizations also decreased after RFCA compared with before RFCA. 12 In the general AFL patient, the success rate of the single‐procedure could reach 91.7%. In contrast, the success rate of AFL RFCA in patients with PH was low.
Several studies have reported catheter ablation of AFL in PH patients, and there have been few studies of long‐term prognosis for mortality after catheter ablation, with the largest study including only 23 PH patients. 8 , 11 , 12 , 13 , 14 To the best of our knowledge, this study is the largest long‐term follow‐up study to evaluate the feasibility of ablation in PH patients with AFL and the predictor of mortality after RFCA.
Methods
Study patients
From April 2013 to August 2021, a total of 67 PH patients with AFL who underwent RFCA for AFL were initially screened for this study at Fuwai Hospital, the National Center for Cardiovascular Diseases of Peking Union Medical College. The diagnosis of pulmonary hypertension was based on the latest guidelines for mPAP≥20 mmHg measured by right heart catheterization (RHC) available at rest. Otherwise, two experienced cardiovascular experts distinguished the level of probability of PH according to the parameters of echocardiography, and only the high probability of PH was selected for this study. 1 In 48 patients, RHC was performed and haemodynamic parameters were obtained to confirm the diagnosis of pulmonary hypertension. Nineteen patients were evaluated by echocardiography for the possibility of pulmonary hypertension with high (n = 13) and intermediate (n = 6) probabilities of PH. Of the selected patients, one had Group 2 PH and one had Group 5 PH and was excluded from this study. Another patient underwent lung transplantation before receiving RFCA and was also excluded. Finally, we selected 46 patients among patients receiving RHC and 12 patients with a high probability of PH according to echocardiography. AFL was preliminarily assessed by electrocardiography (ECG) or Holter monitoring, and typical AFL is characterized by an atrial rate of 250–350 b.p.m., which could show the typical sawtooth pattern without equipotential lines, especially in leads II, III, and avF. Counterclockwise typical AFL was defined as negative in leads II, III, and avF and positive in lead V1, while the ECG of clockwise typical AFL showed the opposite. The final diagnosis was made by experienced electrophysiologists by electrophysiological studies (EPS). The study met the ethical requirements of the Declaration of Helsinki and was approved by the Ethics Committee of Fuwai Hospital, and all patients signed the informed consent.
Procedure of electrophysiological studies and ablation
A 7‐French sheath and an 8‐French sheath were placed into the right femoral vein by Seldinger puncture, followed by placement of the 10‐electrode catheter through a 7‐French sheath into the coronary sinus. A ThermoCool SmartTouch SF (STSF) catheter (Biosense Webster Inc, Diamond Bar, CA, United States) was then positioned in the right atrium through the 8 French sheath. The three‐dimensional electroanatomic mapping system (CARTO, Biosense Webster Inc, Diamond Bar, CA, United States) was used in all AFL cases. The EPS of the AFL was obtained mainly by entrainment mapping, which determined the post pacing interval (PPI, the interval between the last pacing stimulus and the ablation catheter recording the potential at the pacing site) at the tricuspid isthmus and other sites when the ablation catheter was paced 20–30 ms faster than the tachycardia length (TCL). If the PPI was equal to the TCL or the gap was within 10–30 ms, it was considered occult entrainment, indicating that the pacing site was on the reentrant circuit, and if the gap between the PPI and TCL was greater than 10–30 ms, it was considered overt entrainment, indicating that the pacing site was not on the reentrant circuit. Activation mapping of the three‐dimensional electroanatomic system was used to further confirm the diagnosis. After confirmation of the reentrant circuit of AFL, a linear lesion was performed point by point from the tricuspid annulus to the inferior vena cava in cavotricuspid isthmus‐dependent atrial flutter until the bidirectional block between the coronary sinus ostium and the lower lateral right atrium was verified by pacing the ablation catheter and the coronary sinus ostium electrode. 15 Similar requirements were performed at other sites of reentrant circuits. All patients underwent a thorough preoperative evaluation, and EPS and RFCA were performed with stable haemodynamics and no significant discomfort. Transesophageal echocardiography was avoided in patients with a low risk of stroke to reduce clinical deterioration, and a left atrial CT scan was used alternatively to exclude atrial thrombosis. Patient status, blood pressure, heart rate, and oxygen saturation were closely monitored, and nasal cannula or mask oxygen was administered as needed to maintain the oxygen saturation above 90%. Intravenous mild to moderate sedation was used as an alternative due to the relatively large ablation area and long procedure time in some cases. One milligram of midazolam was injected intravenously. Fentanyl 0.5 mg was continuously mixed with 40 mL saline at a pump speed of 10–25 mL/h, depending on the patient's weight. Finally, all catheters were removed, the puncture wound was bandaged properly to avoid bleeding, and the patients had bed rest 6 h after surgery. There were no acute complications in any of the patients.
Postablation management and follow‐up
Patients received standardized PAH‐targeted medications and attended the outpatient clinic regularly or whenever symptoms occurred after RFCA. Holter monitor, ECG, or event monitor recordings were obtained and evaluated for AFL recurrence. Amiodarone was used to restore and maintain sinus rhythm in patients with recurrent arrhythmias as monotherapy or in combination with a rate control agent including digoxin. Some well‐tolerated and willing patients underwent repeat electrophysiology studies and catheter ablation. 16
Statistical analysis
All continuous variables were presented as the means and standard deviations (SD), of which the Levene test was used to test for homogeneity of variance, and categorical variables were presented as numbers and percentages, of which the chi‐squared test was used to test for significance. Significance between continuous variables was tested using one‐way analysis of variance. Univariate and multivariate Cox regression analyses were used to assess risk factors for mortality during follow‐up. The log‐rank test (Mantel–Cox) was used to analyse the Kaplan–Meier survival curve. A two‐tailed P < 0.05 was considered statistically significant, and all statistical analyses were performed with IBM SPSS Statistics 26.
Results
Patient characteristics
The mean age of the 58 patients was 42.8 ± 13.3 years, with a slight female predominance (62.1%). When these patients underwent cardiac function evaluation by cardiologists during their hospitalization, 40 (69.0%) of the patients were classified as WHO class III/IV. Sixteen (27.6%) patients had pericardial effusion measured by echocardiography. The patients had pulmonary artery systolic pressure (PASP) (80.6 ± 27.0 mmHg) measured by echocardiography. The mean NT‐proBNP level was 2285.2 ± 2499.2 pg/mL. More IPAH patients were treated with prostacyclin analogues/receptor agonists (Table 1 ).
Table 1.
Baseline characteristics of the study population
| Characteristic | Overall | PAH‐CHD | IPAH | Others | P value |
|---|---|---|---|---|---|
| No. of patients | 58 | 34 | 19 | 5 | |
| Age (years) | 42.8 ± 13.3 | 41.5 ± 12.8 | 43.6 ± 13.8 | 48.0 ± 16.1 | 0.570 |
| Male (%) | 22 (37.9) | 12 (35.3) | 9 (47.4) | 1 (20.0) | 0.555 |
| BMI (kg/m2) | 22.6 ± 4.0 | 21.5 ± 3.7 | 24.1 ± 3.7 | 23.9 ± 5.5 | 0.055 |
| Hypertension (%) | 7 (12.1) | 1 (2.9) | 5 (26.3) | 1 (20.0) | 0.025 |
| Diabetes (%) | 2 (3.4) | 1 (2.9) | 1 (5.3) | 0 (0.0) | 1.000 |
| CAD (%) | 2 (3.4) | 1 (2.9) | 1 (5.3) | 0 (0.0) | 1.000 |
| Pericardial effusion (%) | 16 (27.6) | 5 (14.7) | 8 (42.1) | 3 (60.0) | 0.020 |
| WHO functional class III–IV (%) | 40 (69.0) | 23 (67.6) | 13 (68.4) | 4 (80.0) | 1.000 |
| NT‐proBNP (pg/mL) | 2285.2 ± 2499.4 | 1702.9 ± 1305.4 | 2581.0 ± 2713.1 | 5121.4 ± 5337.3 | 0.233 |
| TB (μmol/L) | 29.0 ± 20.9 | 26.8 ± 14.0 | 35.5 ± 30.2 | 19.3 ± 12.1 | 0.236 |
| ALT (U/L) | 20.6 ± 12.1 | 20.8 ± 8.7 | 22.0 ± 17.3 | 14.4 ± 7.2 | 0.225 |
| UA (μmol/L) | 423.4 ± 152.9 | 432.8 ± 149.8 | 420.5 ± 174.0 | 371.4 ± 86.9 | 0.708 |
| mPAP (mmHg) | 55.0 ± 17.5 | 55.1 ± 18.9 | 55.9 ± 16.7 | 49.3 ± 13.3 | 0.843 |
| CI (L/min/m2) | 2.90 ± 1.78 | 3.32 ± 2.19 | 2.27 ± 0.60 | 2.77 ± 1.46 | 0.172 |
| LAD (mm) | 37.8 ± 7.6 | 39.3 ± 8.4 | 35.0 ± 5.7 | 38.4 ± 5.6 | 0.141 |
| RVD (mm) | 39.8 ± 9.2 | 38.9 ± 8.6 | 42.2 ± 10.3 | 36.6 ± 9.3 | 0.351 |
| PAD (mm) | 33.1 ± 7.9 | 33.7 ± 8.0 | 31.5 ± 7.5 | 35.0 ± 9.0 | 0.544 |
| LVEF (%) | 61.6 ± 7.8 | 61.2 ± 7.2 | 62.9 ± 9.4 | 59.8 ± 6.3 | 0.647 |
| PASP (mmHg) | 80.6 ± 27.0 | 80.0 ± 29.8 | 82.9 ± 25.0 | 75.8 ± 17.4 | 0.861 |
| ERA (%) | 36 (62.1) | 24 (70.6) | 9 (47.4) | 3 (60.0) | 0.268 |
| PDE‐5i (%) | 37 (63.8) | 19 (55.9) | 14 (73.7) | 4 (80.0) | 0.377 |
| Prostacyclin analogues/receptor agonists (%) | 16 (27.6) | 5 (14.7) | 9 (47.4) | 2 (40.0) | 0.029 |
| Antiarrhythmic class I (%) | 5 (8.6) | 4 (11.8) | 1 (5.3) | 0 (0.0) | 0.777 |
| Antiarrhythmic class III (%) | 17 (29.3) | 6 (17.6) | 8 (42.1) | 3 (60.0) | 0.042 |
ALT, glutamic pyruvic transaminase; CAD, coronary artery disease; CI, cardiac index; ERA, endothelin receptor antagonists; IPAH, idiopathic pulmonary arterial hypertension; LAD, left atrium diameter; LVEF, left ventricle ejection fraction; mPAP, mean pulmonary artery pressure; PAD, pulmonary artery diameter; PAH‐CHD, pulmonary arterial hypertension associated with congenital heart disease; PASP, pulmonary artery systolic pressure; PDE5‐i, phosphodiesterase type 5 inhibitors; RVD, right ventricle; TB, total bilirubin; UA, uric acid.
Types of pulmonary hypertension and atrial flutter
The most common types of PH were pulmonary arterial hypertension associated with congenital heart disease (PAH‐CHD) (n = 34, 58.6%) and idiopathic pulmonary arterial hypertension (IPAH) (n = 19, 32.8%). We included populations with the highest proportion of PAH‐CHD patients (58.6%) compared with previous studies, which was an important feature of our study. After a detailed electrophysiological study, 50 (86.2%) patients were diagnosed with typical AFL and 8 (13.8%) patients were diagnosed with atypical AFL (Figure 1 ). Similar to our study, most of the previously documented AFLs in PH patients were diagnosed as typical AFLs. 8 , 13 A total of 46 patients were diagnosed with persistent AFL and 56 patients received RFCA during AFL episodes. Ten patients underwent intracardiac echocardiography and five patients received DCCV. Acute ablation success was achieved in 53 (91.4%) patients and no acute complications occurred during RFCA (Table 2 ). A total of eight atypical flutters were confirmed by entrainment mapping, with three reentrant circuits located at the right atrial free wall, two reentrant circuits located at the right atrial posterior wall, and one reentrant circuit located at the superior vena cava on high‐density electroanatomic maps during the first procedure. The remaining two reentrant circuits were not confirmed by further high‐density electroanatomic mapping because the patient was unable to tolerate further procedures. Radiofrequency energy was applied from the conduction block line of the posterior right atrial wall or free wall to the inferior vena cava in three patients. One patient underwent linear ablation from the right atrial free wall to the tricuspid annulus, one patient underwent linear ablation from the superior vena cava to the right atrial free wall, and one patient underwent longitudinal radiofrequency application at the superior vena cava.
Figure 1.
Classification of pulmonary hypertension and atrial flutter among the study population.
Table 2.
Procedural characteristics of the included patients
| Characteristic | Overall | PAH‐CHD | IPAH | Others | P value |
|---|---|---|---|---|---|
| No. of patients | 58 | 34 | 19 | 5 | |
| Typical AFL (%) | 50 (86.2) | 30 (88.2) | 17 (89.5) | 3 (60.0) | 0.224 |
| Persistent AFL (%) | 46 (79.3) | 29 (85.3) | 13 (68.4) | 4 (80.0) | 0.324 |
| TCL (ms) | 291.5 ± 50.2 | 290.9 ± 38.0 | 285.7 ± 67.1 | 318.0 ± 51.7 | 0.526 |
| Ablation during AFL (%) | 56 (96.6) | 33 (97.1) | 18 (94.7) | 5 (100.0) | 1.000 |
| ICE (%) | 10 (17.2) | 6 (17.6) | 4 (21.1) | 0 (0.0) | 0.772 |
| Acute success (%) | 53 (91.4) | 29 (85.3) | 19 (100.0) | 5 (100.0) | 0.237 |
| DCCV (%) | 5 (8.6) | 5 (14.7) | 0 (0.0) | 0 (0.0) | 0.237 |
AFL, atrial flutter; DCCV, direct current cardioversion; ICE, intracardiac echocardiography; TCL, tachycardia cycle length.
Atrial flutter recurrence and repeat radiofrequency catheter ablation
After a mean follow‐up of 33.8 months, a total of 22 patients experienced AFL recurrence. Nine of them underwent repeat RFCA and eight of these patients were classified as PAH‐CHD. The subsequent ablation sites were not exactly the same as the initial ablation sites, especially in the PAH‐CHD patients. At a median follow‐up of 34.6 months after the last ablation, none of the patients who underwent repeat RFCA experienced AFL recurrence, and all of these patients survived (Table 3 ). Our results showed a higher recurrence rate than in the general population, both after the first and the last procedure. Radiofrequency energy application from the right atrial free wall to the inferior vena cava was performed in patient 2, patient 5, and patient 8 during the repeat procedure. Patient 9 underwent linear ablation from the posterior wall of the right atrium to the inferior vena cava and linear ablation from the superior vena cava through the posterior wall of the right atrium to the inferior vena cava.
Table 3.
Clinical information and follow‐up data of patients receiving repeat RFCA
| Characteristic | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 |
|---|---|---|---|---|---|---|---|---|---|
| Age (years) | 51 | 52 | 28 | 47 | 29 | 35 | 28 | 51 | 46 |
| Gender | M | M | F | M | M | M | F | F | M |
| BMI (kg/m2) | 24.4 | 21.2 | 25.5 | 20.1 | 25.1 | 22.8 | 21.6 | 27.7 | 18.8 |
| PH type | PAH‐CHD | PAH‐CHD | PAH‐CHD | PAH‐CHD | PAH‐CHD | IPAH | PAH‐CHD | PAH‐CHD | PAH‐CHD |
| PASP (mmHg) | 82 | 135 | 62 | 85 | 102 | 104 | 98 | 42 | 111 |
| NT‐proBNP (pg/mL) | 843.9 | 2416.4 | 234.0 | 1411.0 | 1025.0 | 2645.0 | 3514.0 | 1613.0 | 1819.0 |
| Cardiac surgery before first ablation | No | Yes | Yes | No | Yes | No | No | Yes | Yes |
| First ablation sites | CTI | CTI | CTI | CTI | Right atrial free wall | CTI | CTI | CTI | CTI |
| Number of AFL ablations | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 2 | 4 |
| Subsequent ablation sites | CTI | CTI, right atrial free wall | CTI | CTI | CTI, right atrial free wall | CTI | CTI | right atrial free wall | CTI, right atrial posterior and free wall |
| AFL recurrence after last ablation | No | No | No | No | No | No | No | No | No |
| Follow‐up periods from last ablation (months) | 92.3 | 16.3 | 47.0 | 16.2 | 34.4 | 25.4 | 30.2 | 29.7 | 19.9 |
AFL, atrial flutter; CTI, cavotricuspid isthmus; IPAH, idiopathic pulmonary arterial hypertension; PAH‐CHD, pulmonary arterial hypertension associated with congenital heart disease; PASP, pulmonary artery systolic pressure.
Long term survival outcome of pulmonary hypertension patients with atrial flutter after radiofrequency catheter ablation
Unfortunately, 14 patients died during the follow‐up period. No long‐term ablation‐related complications were found in any of the patients. Univariate and multivariate Cox regression analyses showed that NT‐proBNP (HR: 1.00024, 95% CI: 1.00008–1.00041, P = 0.004), pulmonary artery systolic pressure (PASP) (HR: 1.048, 95% CI: 1. 020–1.076, P = 0.001), and IPAH (vs. PAH‐CHD, HR: 7.720, 95% CI: 1.437–41.483, P = 0.017) were independent predictors of all‐cause mortality in PH patients with AFL after RFCA. However, recurrence of AFL after the last ablation was not associated with all‐cause mortality (HR: 0.884, 95% CI: 0.244–3.206, P = 0.851) (Table 4 ). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of PASP for predicting all‐cause mortality was 0.708 (95% CI: 0.533–0.884, P < 0.001) (Figure 2 ). There was no significant difference in the Kaplan–Meier curves for all‐cause mortality between patients with AFL recurrence after the last ablation and those without (P = 0.851). Patients with higher PASP (≥110 mmHg) (P = 0.001) and IPAH (P = 0.005) were associated with higher all‐cause mortality (Figure 3 ).
Table 4.
Univariate and multivariate COX regression analysis of all‐cause mortality after RFCA
| Variables | Univariate model | Multivariate model | ||
|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | |
| Age (years) | 1.028 (0.985–1.073) | 0.208 | ||
| BMI (kg/m2) | 0.925 (0.810–1.057) | 0.253 | ||
| NT‐proBNP (pg/mL) | 1.00025 (1.00013–1.00038) | <0.001 | 1.00024 (1.00008–1.00041) | 0.004 |
| ALT (U/L) | 0.962 (0.907–1.022) | 0.208 | ||
| UA (μmol/L) | 0.999 (0.996–1.002) | 0.596 | ||
| mPAP (mmHg) | 1.026 (0.987–1.065) | 0.194 | ||
| CI (L/min/m2) | 0.562 (0.233–1.353) | 0.199 | ||
| LAD (mm) | 0.922 (0.837–1.015) | 0.099 | ||
| RVD (mm) | 1.032 (0.974–1.093) | 0.283 | ||
| PAD (mm) | 0.984 (0.917–1.055) | 0.650 | ||
| PASP (mmHg) | 1.025 (1.007–1.043) | 0.006 | 1.048 (1.020–1.076) | 0.001 |
| TCL (ms) | 1.011 (0.999–1.023) | 0.075 | ||
| PH type (IPAH vs. PAH‐CHD) | 4.829 (1.385–16.837) | 0.013 | 7.720 (1.437–41.483) | 0.017 |
| AFL type (typical vs. atypical) | 0.967 (0.212–4.412) | 0.966 | ||
| WHO functional class (III/IV vs. I/II) | 1.700 (0.473–6.109) | 0.416 | ||
| AFL recurrence after last ablation | 0.884 (0.244–3.206) | 0.851 | ||
AFL, atrial flutter; ALT, glutamic pyruvic transaminase; CI, cardiac index; CI, confidence interval; HR, hazard ratio; IPAH, idiopathic pulmonary arterial hypertension; LAD, left atrium diameter; mPAP, mean pulmonary artery pressure; PAD, pulmonary artery diameter; PAH‐CHD, pulmonary arterial hypertension associated with congenital heart disease; PASP, pulmonary artery systolic pressure; RVD, right ventricle; TCL, tachycardia cycle length; UA, uric acid.
Figure 2.
The predictive efficacy of PASP for all‐cause mortality was evaluated by the ROC curve analysis.
Figure 3.
Kaplan–Meier analysis of all‐cause mortality in recurrence condition (A), PASP (B) and PH types (C). AFL, atrial flutter; IPAH, idiopathic pulmonary arterial hypertension; PAH‐CHD, pulmonary arterial hypertension associated with congenital heart disease; PASP, pulmonary artery systolic pressure.
Discussion
The main findings of this study were as follows 1 : RFCA was feasible in PH patients with AFL, and repeat RFCA in patients with recurrent AFL was effective in maintaining sinus rhythm. 2 NT‐proBNP, PASP, and IPAH were independent predictors of all‐cause mortality after RFCA in these patients, but recurrence of AFL after the last ablation was not associated with all‐cause mortality after RFCA.
Feasibility of radiofrequency catheter ablation
The incidence of supraventricular arrhythmias (SVT) increases with age, and in a 5‐year retrospective study of 239 patients with PAH and CTEPH, new‐onset atrial flutter and atrial fibrillation were independent risk factors for death and often led to clinical deterioration and right heart failure. 9 , 17 The treatments considered safe and effective included antiarrhythmic drugs, DCCV, and radiofrequency ablation. 9 In a previous study of 14 patients with a one‐year follow‐up, ablation of AFL showed a good success rate, with a one‐year recurrence rate of 50%, and was able to reduce SPAP and BNP. The mortality of PH patients with AFL within 1 year was higher than that of PH patients without AFL. 11 Antiarrhythmic medication, serum BNP levels, and the number of hospitalizations were significantly reduced compared with the preprocedure levels during a median follow‐up of 5.1 years after SVT ablation in PH patients. 12 AFL patients with PAH needed more procedure time, needed more ablation time, and had more ablation lesions than AFL patients without PAH, but bidirectional block of the cavotricuspid isthmus was achieved in all patients, including those with PAH. 8 In a comparative study of 84 PAH or CTEPH patients with AFL/AF, rhythm control with DCCV and amiodarone improved cardiac function and survival compared with rate control, with DCCV having a higher rate of sinus rhythm restoration than amiodarone. The right atrial area independently predicts the recurrence of AF/AFL. 10 However, there are currently insufficient studies of RFCA in PH patients with AFL, and many of them included other SVTs, such as atrial fibrillation and atrial tachycardia. In addition, there are not enough studies on recurrence and mortality after RFCA. To our knowledge, our study included the largest number of PH patients with AFL. In our study, a total of 58 PAH or CTEPH patients with AFL were included, and recurrence and mortality data were also obtained. The freedom from recurrence rate was 62.1% after the first procedure and 77.6% after the last procedure, which showed an excellent ablation effect and further confirmed that RFCA could be the preferred treatment for these patients. The ablation success rate in our cohort was lower than that in the general population of previous AFL catheter ablation studies, and this result was similar to the results of previous studies enrolling PH patients. We speculated that PH may cause right atrial enlargement and remodelling, increasing the difficulty of catheter manipulation and interfering with the transmurality of ablation lesions.
Effectiveness of repeated radiofrequency catheter ablation
We also found that repeat ablation was feasible in patients with AFL recurrence, but the ablation target may be different from the first procedure in patients with PAH‐CHD. In PH patients with AF/AFL, clinical arrhythmia ablation alone and clinical arrhythmia plus substrate‐based ablation strategies showed no difference in terms of recurrence and survival. 13 We proposed a new ablation strategy in which both the CTI and the right atrial area of conduction block are ablated during RFCA of the AFL in patients undergoing cardiac surgery prior to ablation. Our hypothesis did not conflict with this negative study because we primarily targeted patients with PAH‐CHD undergoing cardiac surgery, and the populations enrolled in the study were IPAH, CTEPH, and Group3 PH.
Atrial flutter recurrence and mortality
In patients with PH, episodes of supraventricular arrhythmia (SVA) were associated with clinical detection and right heart failure, and cumulative mortality was lower when sinus rhythm was restored during a mean follow‐up of 26 months. In contrast, 9 of 11 patients with persistent atrial fibrillation died of right heart failure after 11 months of follow‐up, suggesting that persistent atrial fibrillation may be associated with a high risk of right ventricular failure and mortality. 18 In a retrospective cohort study, sinus rhythm was successfully restored in 21/24 (88%) new‐onset AFL patients and 16/24 (67%) new‐onset AF patients, of which 16 AFL patients received RFCA. New‐onset AFL and AF were independent risk factors for mortality and often led to clinical deterioration and right heart failure. Patients with persistent atrial fibrillation had a higher mortality rate than those who had sinus rhythm restored. 17 PH patients with AF/AFL manifested a larger left atrial volume index and right atrial area than PH patients without AF/AFL, and AF/AFL was associated with an increased risk of mortality whether diagnosed before or after PH. 19 Increases in the right ventricular diameter, left atrial area, right atrial pressure, and pulmonary vascular resistance were associated with an increased risk of SVA, suggesting that SVA, especially focal atrial tachycardia, AFL, and AF, are the result of increased pulmonary vascular resistance and cardiac remodelling. 7 A large number of previous retrospective studies have shown that the survival rate of PH patients with SVA was lower than that of patients without SVA, which generally led to clinical deterioration and may be associated with an increased risk of right heart failure. Restoration and maintenance of sinus rhythm are important therapeutic goals in PH patients with SVA. Antiarrhythmic drugs, DCCV and RFCA could be used as safe and effective methods. 9
Previous studies suggested that new‐onset atrial arrhythmias could lead to clinical deterioration and that restoration of sinus rhythm was associated with improvement in functional class. Our study showed a completely novel conclusion that AFL recurrence after RFCA in PH patients with AFL was not associated with mortality. There may be three reasons for our findings. First, we included only 58 PH patients in this study, and this study was a single‐centre retrospective study. Second, we used a dichotomous variable to describe AFL recurrence in our study, and isolated AFL recurrence may not reflect the true arrhythmia burden. AFL burden may be a more accurate variable to reflect a patient's arrhythmia status. 20 Third, typical AFL is predominantly right atrial reentrant tachycardia with less electrophysiological involvement of the left atrium than AF, which may explain the better prognosis of recurrent AFL than AF.
Pulmonary arterial hypertension associated with congenital heart disease versus idiopathic pulmonary arterial hypertension
PAH patients with atrial arrhythmias had increased right atrial pressure, PAWP, NT‐proBNP and thyroid disease. IPAH patients with atrial arrhythmias and systemic sclerosis‐related PAH patients without atrial arrhythmias had similar long‐term mortality, and systemic sclerosis‐related PAH patients with atrial arrhythmias had the worst prognosis. 21 A cohort study of 364 PAH patients showed that IPAH patients had a shorter 6‐min walk distance, lower blood oxygen saturation, and higher BNP than PAH‐CHD patients. Survival rates were higher in PAH‐CHD patients than in IPAH patients, and Kaplan–Meier survival analysis suggested that 5‐year survival estimates for patients with IPAH and PAH‐CHD were 74.3% and 92.6%, respectively. Patients aged <18 years at diagnosis of IPAH had worse survival than adult patients. 22 A retrospective study of PH found that PAH‐CHD patients had better survival than IPAH patients during a median follow‐up of 11.7 years, with slightly different haemodynamic measures between the two groups, the latter being slightly worse. Children with Eisenmenger's syndrome had worse survival than adults. 23
This showed that the prognosis of different types of PH was different, which was similar to our study. After receiving congenital heart disease correction treatment, the high blood flow of pulmonary circulation and pulmonary vascular remodelling in PAH‐CHD patients were inhibited, while the pathogenesis of IPAH patients was not clearly demonstrated, and it was difficult to inhibit or even reverse pulmonary vascular remodelling. Compared with the IPAH or HPAH cohort, patients with Eisenmenger's syndrome had a lower mean right atrial pressure, higher mean pulmonary artery pressure, higher pulmonary vascular resistance, and lower arterial oxygen saturation. During the follow‐up period, survival rates were similar between the IPAH or HPAH group and the PAH‐CHD group. 24 However, all patients with PAH‐CHD included in this study progressed to Eisenmenger's syndrome, and the populations in our study did not progress to bidirectional shunts or right‐to‐left shunts.
Limitations
The study has several limitations. First, this was a single‐centre retrospective cohort study, and since PAH‐CHD patients accounted for 58.6% of the total patients we included, the representation of our cohort may be potentially biased. Second, we included a limited number of cases because of the small population base of PH patients and the low incidence of arrhythmias in PH patients. In developed countries, the incidence of PAH is 1.1–7.6 per million people per year, and the prevalence is 6.6–26.0 per million people. 25 In a retrospective study involving patients with PH, the incidence of AFL in PAH and CTEPH patients ranged from 3.8% to 5.4%. The overall number of PH patients diagnosed with AFL who underwent RFCA was small, considering that some patients did not receive timely diagnosis and appropriate treatment due to economic or technical reasons. Third, the lack of RHC data in some patients limited the role of haemodynamic parameters in the regression analysis. Finally, we assessed the patients for recurrence of atrial arrhythmias based on ECG or Holter, and arrhythmia episodes may be ignored in some patients. We categorized patients into recurrence and nonrecurrence groups, which may have lost some information, such as the AFL burden.
Conclusion
Repeat RFCA was safe and feasible in patients with recurrent AFL. High PASP and IPAH independently predicted all‐cause mortality after RFCA, with no correlation with recurrent AFL.
Funding
The study is funded by National Natural Science Foundation of China (82000064 and U1913210).
Conflict of interest
All authors declare no conflicts of interest.
Zhang, A. , Ding, L. , Zhang, H. , Mi, L. , Yu, F. , and Tang, M. (2024) Radiofrequency catheter ablation for pulmonary hypertension patients with atrial flutter. ESC Heart Failure, 11: 883–892. 10.1002/ehf2.14659.
Aikai Zhang and Lei Ding equally contributed to the study.
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