Incidence of phrenic nerve injury during pulmonary vein isolation using different cryoballoons: data from a large prospective ablation registry.

AIMS: Phrenic nerve injury (PNI) is the most common complication during cryoballoon ablation. Currently, two cryoballoon systems are available, yet the difference is unclear. We sought to compare the acute procedural efficacy and safety of the two cryoballoons. METHODS: This prospective observational study consisted of 2,555 consecutive atrial fibrillation (AF) patients undergoing pulmonary vein isolation (PVI) using either conventional (Arctic Front Advance) (AFA-CB) or novel cryoballoons (POLARx) (POLARx-CB) at 19 centers between January 2022 and October 2023. RESULTS: Among 2,555 patients (68.8 ± 10.9 years, 1,740 men, paroxysmal AF[PAF] 1,670 patients), PVIs were performed by the AFA-CB and POLARx-CB in 1,358 and 1,197 patients, respectively. Touch-up ablation was required in 299(11.7%) patients. The touch-up rate was significantly lower for POLARx-CB than AFA-CB (9.5% vs. 13.6%, p = 0.002), especially for right inferior PVs (RIPVs). The touch-up rate was significantly lower for PAF than non-PAF (8.8% vs. 17.2%, P < 0.001) and was similar between the two cryoballoons in non-PAF patients. Right PNI occurred in 64(2.5%) patients and 22(0.9%) were symptomatic. It occurred during the right superior PV (RSPV) ablation in 39(1.5%) patients. The incidence was significantly higher for POLARx-CB than AFA-CB (3.8% vs. 1.3%, P < 0.001) as was the incidence of symptomatic PNI (1.7% vs. 0.1%, P < 0.001). The difference was significant during RSPV (2.5% vs. 0.7%, P < 0.001) but not RIPV ablation. The PNI recovered more quickly for the AFA-CB than POLARx-CB. CONCLUSIONS: Our study demonstrated a significantly higher incidence of right PNI and lower touch-up rate for the POLARx-CB than AFA-CB in the real-world clinical practice.

Adjunctive posterior wall isolation for the treatment of persistent and longstanding persistent atrial fibrillation (CORNERSTONE AF) trial: Design and rationale.

BACKGROUND: A left atrial posterior wall isolation (LAPWI) is one of the atrial fibrillation (AF) ablation strategies. HYPOTHESIS: We hypothesized that an additional empirical LAPWI would increase the freedom from recurrent atrial arrhythmias as compared to standard AF ablation in persistent AF patients. METHODS: The CORNERSTONE AF study is a prospective, randomized, multicenter study investigating patients with AF persisting for >7 days and <3 years undergoing first-time AF ablation. They will be randomized to pulmonary vein isolation (PVI) or PVI + LAPWI in a 1:1 manner. Although PVI can be performed with either radiofrequency catheters or cryoballoons, only radiofrequency catheters will be permitted to achieve LAPWIs. Additional focal ablation targeting non-pulmonary vein triggers will be allowed. A total of 516 patients will be enrolled in 17 centers between August 2022 and February 2024 based on the calculation with 80% power, considering the assumption that 65% and 75% of the PVI and PVI + LAPWI group patients will be free from atrial arrhythmia recurrence 18-months postprocedure (10% of dropout). The primary endpoint is freedom from documented atrial arrhythmias 18 months postsingle procedures. Clinical follow-up will include 7-day ambulatory electrocardiograms and routine outpatient consultations by electrophysiologists at 1, 3, 6, 9, 12, and 18 months postprocedure. RESULTS: As of August 2023, a total of 331 patients (68 ± 9 years, 270 men, 43 longstanding persistent AF) have been enrolled. CONCLUSIONS: The CORNERSTONE AF study is a prospective, randomized, multicenter trial designed to evaluate the efficacy and safety of an adjunctive empirical LAPWI following standard AF ablation in persistent AF patients.

Novel method to avoid serious injurious effects on the atrioventricular nodal (AVN) conduction during catheter ablation of the AVN slow pathway utilizing cryofreezing energy.

BACKGROUND: Slow pathway elimination of the atrioventricular node (AVN) is essential to treat AVN reentrant tachycardia (AVNRT). However, injury to the AVN conduction (IAVN) is one of the serious complications. Cryofreezing energy is expected to reduce the incidence of IAVN. This study aimed to investigate the usefulness of a novel method to avoid IAVN during cryoablation of AVNRT. METHODS: A total of 157 patients (average age, 65.8 years; male, 71) suffering from AVNRT were included. Once the AVNRT terminated during cryo-ablation, then rapid atrial constant pacing (RACP) was performed during freezing at a rate lower 10 bpm than that inducing Wenchebach AV block in 74 (47.1 %) patients (Group A). The RACP rate was decreasingly reduced by 10 bpm in case of the occurrence of IAVN. When the RACP reached 100 bpm, the cryoablation was prematurely terminated. Group B patients (83 = 52.9 %) underwent cryoablation during sinus rhythm. All patients were allocated in a randomized fashion. We compared the severity of the IAVN between Groups A and B. RESULTS: There were no significant differences at 12 months regarding the freedom from the AVNRT between Groups A and B. However, the duration of the IAVN was significantly longer in Group B than A (p = 0.02). There were no significant differences regarding the distance between the His recording sites and successful ablation sites between Groups A and B. No permanent IAVN requiring pacemaker implantation was provoked in either group. CONCLUSION: RACP was useful to avoid sustained and serious IAVN during cryoablation of AVNRT.

Edoxaban eliminates hypercoagulability evoked by transient temperature changes in human whole blood.

Background: Thrombosis is a common critical complication relating to radiofrequency catheter ablation and cryoablation. There is a possibility that high-temperature stimulation during radiofrequency ablation or low-temperature stimulation during cryoablation may affect the coagulability of blood. In this study, we aimed to determine the impacts of transient temperature stimulations on the coagulability of whole blood and to clarify if edoxaban suppressed the hypercoagulability. Methods: Citrated blood samples were drawn from 41 healthy subjects. Some blood samples were mixed with tissue factor (TF) and several concentrations of edoxaban (50, 100, and 200 ng/mL). Blood samples were exposed to several temperature stimulations for 1 min: heat stimulation (50°C) or cryostimulation (-20°C), and compared with control (37°C). Repeated cryostimulations or sequential cryo- and heat stimulation were also applied. Coagulability of whole blood was measured using a dielectric blood coagulometry. As an index of coagulability, the end of acceleration time (EAT) was used. Results: Both heat- and cryostimulations significantly shortened the EAT compared to the control, indicating that hypercoagulability was induced by temperature stimulations. Application of TF enhanced and extended the hypercoagulability after the temperature stimulations. Sequential application of cryo- followed by heat stimulation further enhanced the hypercoagulability of blood. Application of edoxaban increased the EAT in a concentration-dependent manner in control condition. Edoxaban at 100 or 200 ng/mL completely suppressed the shortening of EAT evoked by these temperature stimulations. Conclusion: Transient temperature stimulations evoked hypercoagulability regardless of cryo- or heat stimulation. Edoxaban with 100 ng/mL or more eliminated this temperature-stimulated hypercoagulability.

Paradigm Shift for Catheter Ablation of Atypical Atrioventricular Nodal Re-Entrant Tachycardia: 3-Dimensional Mapping-Based Ablation.

BACKGROUND: In current practice, the ablation target of atypical atrioventricular nodal re-entrant tachycardia (AVNRT) is the earliest atrial activation site in the coronary sinus (CS) or conventional slow pathway region. OBJECTIVES: The purposes of this study were to map the site of earliest retrograde atrial activation using electroanatomic three-dimensional mapping during atypical AVNRT and to evaluate successful ablation sites. METHODS: A total of 42 patients with a total of 49 AVNRTs (slow/fast: 30; fast/slow: 15; slow/slow: 4) underwent electrophysiological study and ablation. Among them there were 14 patients (10 women; 60 ± 19 years of age) in whom 19 atypical AVNRT (fast/slow: 15; slow/slow: 4) were induced. RESULTS: The intracardiac electrocardiograms or three-dimensional mapping of the exit site during tachycardia revealed that 7 patients had exit sites solely inside the CS (left inferior extension [LIE]), 3 solely in the right postero-septal tricuspid annulus (TA; right inferior extension [RIE]), and 4 had both LIE and RIE exits. The distance from the CS ostium to LIE exits was 14 ± 6 mm. RIE exits were located on the TA posterior to the CS ostium (between 5 and 6 o'clock in the left anterior oblique projection). Ablation targeting these exits or conventional slow pathway succeeded in long-term elimination of AVNRT in 13 of the 14 patients (93%). There were no complications. CONCLUSIONS: Catheter ablation targeting the exit sites of LIE or RIE mapped at the CS or TA holds promise as an effective and safe alternative approach to the current targets of ablation for atypical AVNRT cases.

Initial multicenter clinical experience with the first-generation endoscopic guided laser balloon in Japan.

BACKGROUND: Isolation of the pulmonary veins (PVs) is the golden standard for atrial fibrillation (AF) ablation. To achieve a permanent PV isolation, the endoscopic guided HeartLight laser balloon system was invented. We analyzed the safety and efficacy of this laser balloon system. METHODS AND RESULTS: Three hundred four patients from 21 investigational sites inside Japan were enrolled in this study. One thousand sixty-two out of 1175 PVs (90.4%) were isolated using the HeartLight laser balloon. The isolation rate of the left superior, left inferior, right superior, and right inferior PVs was 87.8%, 91.3%, 91.6%, and 92.1%, respectively. The procedure time, defined as the time from the venous access to taking out the balloon, was 155 ± 39 min. The fluoroscopic time was 44 ± 25 min. The mean follow-up period was 309 ± 125 days. The freedom from AF recurrence at 3 months was 89.0% and at 12 months 82.1%. Adverse events occurred in 22 patients (7.2%) including phrenic nerve injury lasting more than 3 months in 1.6% and strokes in 1.0% of the patients. CONCLUSIONS: This initial experience demonstrated that the laser balloon ablation was feasible for PV isolation in Japanese AF patients.

The utility of combining continuous wavelet transform analysis and high-density voltage map in predicting the long-term outcomes after ablation of persistent atrial fibrillation.

BACKGROUND: Continuous wavelet transform (CWT) analysis is a frequency analysis to detect areas of stable high-frequent activity (stable pseudo frequency [sPF]) during atrial fibrillation (AF). As previously reported, patients with the highest sPF area in pulmonary veins (PV) showed better short-term outcomes after PV isolation (PVI). This study sought to evaluate the efficacy of CWT analysis in predicting the long-term (2 years) outcomes after PVI. We also combined the left atrial (LA) voltage map with CWT analysis to further predict the outcome. METHODS: Persistent AF patients (n = 109, age 65 ± 10) underwent a CWT analysis at PVs and 8 LA sites during AF for pre-PVI analysis. After PVI during AF, CWT analysis was performed again in the LA as post-PVI analysis and was compared with pre-PVI analysis. A sinus voltage map of LA was created after cardioversion. RESULTS: Seventy patients had the highest sPF within PVs (PV-dominant group), while 39 patients had the highest sPF outside PVs (LA-dominant group). The global frequency in the LA showed a significant decrease after PVI only in PV-dominant group (6.55 ± 0.27 to 6.43 ± 0.37, P < 0.01). AF-free survival was better in PV-dominant group than LA-dominant group at 2-year follow-up (87.1% vs. 64.3%, P < 0.002). This trend was recognized throughout all degrees of low voltage area in the LA (LA-LVA), and AF-free survival was well predicted by combining CWT analysis and LA-LVA. CONCLUSIONS: By combining CWT analysis and sinus LA-LVA, the long-term AF-free survival after PVI was well stratified and predicted.

Orthodromic AVRT With 2 Different Wide QRS Complexes Caused by Bilateral Bystander Nodoventricular Pathways.

We present a case of orthodromic atrioventricular re-entrant tachycardia exhibiting both right and left bundle branch block pattern wide QRS morphologies caused by bilateral bystander nodoventricular (NV) accessory pathways. These wide QRS morphologies came from pre-excitation accompanied by delta waves. In the context of NV accessory pathways, left-sided manifest NV accessory pathways are rare.

Neutrophil extracellular traps-mediated Beclin-1 suppression aggravates atherosclerosis by inhibiting macrophage autophagy.

A growing body of evidence suggests that neutrophil extracellular traps (NETs) critically contribute to the development of atherosclerosis. However, the detailed mechanism of how NETs promote atherogenesis remains unknown. In this study, we explored the role of NETs for promoting atherosclerosis by modulating the activity of autophagy in macrophages. NETs were effectively induced by a nicotine administration to the HL-60 cell-derived neutrophil-like cells. Treatment with NETs markedly suppressed both autophagosome formation and autophagosome-lysosome fusion in 7-ketocholesterol-treated macrophages, which are accompanied by the enhancement of inflammasome activity. NETs upregulate epidermal growth factor receptor (EGFR) activity, which enhances Beclin-1 phosphorylation of the tyrosine residues of Beclin-1 by EGFR, inhibits the PI3 kinase activity of the Beclin1-Vps34 complex, and suppresses autophagosome formation in macrophages. Furthermore, NET-induced activation of EGFR allows Rubicon to increase its expression, thereby suppressing autophagosome-lysosome fusion. In vivo experiments revealed that the suppression of NET formation by ablating peptidyl arginine deiminase-4 in neutrophil leukocytes resulted in the attenuation of atherosclerotic plaques in a nicotine-administered HFD-fed ApoE -/- mice. Taken together, these results suggest that NET-mediated EGFR-Beclin-1 signaling in the macrophages promotes atherogenesis by autophagy inhibition-mediated inflammasome activation.

Utility of Simultaneous Biatrial Atrial Anti-Tachycardia Pacing for the Termination of Atrial Fibrillation during Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Atrial anti-tachycardia pacing (A-ATP) of the right atrium (RA) has been shown to decrease the burden of atrial fibrillation (AF) in patients with dual-chamber pacemakers. The aim of this study is to identify the novel predictors of effective A-ATP for terminating AF in patients with AF undergoing catheter ablation. METHODS: This study included 41 consecutive patients undergoing a first ablation procedure for paroxysmal (PAF: n = 21) or persistent (PEF: n = 20) AF. We prospectively evaluated predictors of AF termination after A-ATP. The coefficient of variation (CoV = SD/mean × 100) of the dominant frequencies (DFs) was calculated to evaluate the variability in atrial activation. RESULTS: AF was terminated by A-ATP in 29% of PAF and 5% of PEF patients. In these patients, simultaneous high-rate pacing from the RA and the coronary sinus (CS) terminated AF in 71% of patients, in whom the mean AF cycle length (CL) before A-ATP was longer (214 ± 23 vs. 177 ± 35 ms, p = 0.02) and became slower after A-ATP (234 ± 37 vs. 176 ± 32 ms, p < 0.01), compared to unsuccessful patients. The CoV of the DFs before A-ATP were lower in both RA (6.2 ± 2.0 vs. 15.3 ± 7.9, p = 0.02) and CS (11.0 ± 7.9 vs. 24.3 ± 9.3, p < 0.01) in successful patients. CONCLUSIONS: Simultaneous biatrial A-ATP from the RA and CS could terminate AF in patients with PAF. The predictors for successful termination include longer AF CL and higher AF stability.

Cryoballoon ablation for paroxysmal atrial fibrillation in Japan: 2-year safety and efficacy results from the Cryo AF Global Registry.

PURPOSE: Catheter ablation is a recommended rhythm control therapy after failed or intolerant antiarrhythmic drug (AAD) treatment for patients with atrial fibrillation (AF). This study evaluates clinical performance and safety of pulmonary vein isolation (PVI) using the cryoballoon (Arctic Front Advance) in Japan. METHODS: Cryo AF Global Registry is a prospective, multi-center registry. Patients with paroxysmal AF (PAF) were treated at 10 Japanese hospitals. Efficacy was evaluated by freedom from a ≥ 30-s recurrence of AF/atrial flutter (AFL)/atrial tachycardia (AT), AF-related symptoms, and quality of life using the EQ-5D-3L questionnaire. The safety endpoint was serious device- and procedure-related adverse events. RESULTS: The study included 352 patients with PAF (65 ± 10 years of age, 36% female, 36% without prior failure of AAD). Mean duration since first diagnosis of AF was 3.0 ± 5.5 years. Serious device- and procedure-related adverse event rate was 2.6% (95% CI: 1.2-4.8%). Freedom from AF/AFL/AT was 88.5% (95% CI: 84.7-91.4%) at 12 months and 86.7% (95% CI: 81.1-90.8%) at 24 months. The number of patients with ≥ 1 AF symptom was significantly decreased from 88% at enrollment to 22% (p < 0.01) at 12-month follow-up. General quality of life using EQ-5D did not improve significantly after 12 months in the summary score. However, in the visual analog scale score, there was improvement (5.8 ± 18.4; p < 0.01). CONCLUSIONS: This study demonstrates that cryoablation used for PVI is a safe and effective treatment in real-world use for patients with PAF in Japan.

Pulmonary Artery Isolation for Polymorphic Outflow Tract Ventricular Tachycardia.

Malignant ventricular arrhythmias arising from the pulmonary artery rarely occur in patients without structural heart disease. We highlight the feasibility and efficacy of a circular catheter-guided pulmonary artery isolation procedure for frequent premature ventricular contractions and polymorphic ventricular tachycardia causing syncope. (Level of Difficulty: Advanced.).

Genotype-Phenotype Correlation of SCN5A Genotype in Patients With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands.

BACKGROUND: Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event. METHODS: Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and SCN5A genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed. RESULTS: The study group comprised 392 probands: 92 (23.5%) SCN5A+(44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A-.SCN5A missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with SCN5A- (11.4% versus 3%, P=0.023). The proportion of females was higher among patients with P/LP compared with SCN5A- (18.2% versus 6.3%, P=0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A- (41.9% versus 16.8%, P<0.001). A higher proportion of patients with P/LP were White compared with SCN5A- (87.5% versus 47%, P<0.001). Ethnicity (odds ratio, 5.41 [2.8-11.19], P<0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28-5.82], P=0.009) were independent variables associated with P/LP genotype following logistic regression. CONCLUSIONS: The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with SCN5A-. In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.

Linagliptin, A Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor, Ameliorates Experimental Autoimmune Myocarditis.

This study sought to show the mechanism of how to ameliorate experimental autoimmune myocarditis (EAM) by administering dipeptidyl peptidase (DPP)-4 inhibitor linagliptin. The number of RAR-related orphan nuclear receptor gamma-positive Th17 cells infiltrated to the EAM myocardium was significantly attenuated by linagliptin treatment. Tandem mass spectrometry-based analysis demonstrated that DPP-4 binds to cathepsin G in EAM hearts, thereby protecting cathepsin G activity through inhibiting SerpinA3N activity. Linagliptin suppresses oxidative stress in EAM hearts as well. Thus, we found that DPP-4 plays a detrimental role in the progression of EAM by interacting with cathepsin G, which, in turn, suppresses SerpinA3N activity.

Geriatric nutritional risk index as a predictor of arrhythmia recurrence after catheter ablation of atrial fibrillation.

BACKGROUND AND AIMS: The nutritional risk of patients who undergo atrial fibrillation (AF) ablation varies. Its impact on the recurrence after ablation is unclear. We sought to evaluate the relationship between the nutritional risk and arrhythmia recurrence in patients who undergo AF ablation. METHODS AND RESULTS: We enrolled 538 patients (median 67 years, 69.9% male) who underwent their first AF ablation. Their nutritional risk was evaluated using the pre-procedural geriatric nutritional risk index (GNRI), and the patients were classified into two groups: No-nutritional risk (GNRI â‰§ 98) and Nutritional risk (GNRI < 98). The primary endpoint was a recurrence of an arrhythmia, and its relationship to the nutritional risk was evaluated. We used propensity-score matching to adjust for differences between patients with a GNRI-based nutritional risk and those without a nutritional risk. A nutritional risk was found in 10.6% of the patients, whereas the remaining 89.4% had no-nutritional risk. During a mean follow-up of 422 days, 91 patients experienced arrhythmia recurrences. The patients with a nutritional risk had a significantly higher arrhythmia recurrence rate both in the entire study cohort (Log-rank p = 0.001) and propensity-matched cohort (Log-rank p = 0.006). In a Cox proportional hazard analysis, the nutritional risk independently predicted arrhythmia recurrences in the entire study cohort (hazard ratio [HR]: 3.91, 95% confidence interval [CI]: 1.84-8.35, p < 0.001) and propensity-matched cohort (HR: 6.49, 95% CI: 1.42-29.8, p = 0.016). CONCLUSION: A pre-procedural malnutrition risk was significantly associated with increased arrhythmia recurrences in patients who underwent AF ablation.

Vagal Reactions During Laser Balloon Ablation in Patients with Paroxysmal Atrial Fibrillation.

Radiofrequency and cryoballoon applications around the pulmonary veins (PVs) could provoke a vagal reflex (VR) by modulating the intrinsic cardiac autonomic nervous system (ICANS).This study aimed to investigate the incidence, timing, and clinical impact of a VR provoked by a laser balloon application for a PV isolation (PVI).A total of 92 consecutive paroxysmal atrial fibrillation (PAF) patients underwent a laser balloon PVI of PAF. Acute changes in the heart rate and blood pressure were recorded. The heart rate variability (HRV) was tested by Holter ECGs before and at three months following the ablation. Three hundred forty-five out of 363 PVs were successfully isolated (97%) with laser balloon applications. A VR such as sinus bradycardia (26.1%), transient sinus arrest (9.8%), transient atrioventricular block (1.1%), or a blood pressure reduction (8.7%) was observed during the laser balloon applications for the PVI. The follow-up ended at 12 months. The HRV attenuation was comparable before and at three months after the ablation procedure between that with and without a VR (P = 0.14). The PAF recurrence rate was also comparable between the two groups (P = 0.882).The laser balloon PVI often provoked a VR, however, the modulation of the ICANS was temporary and for up to three months as measured by the HRV changes after the ablation, and the freedom from any atrial fibrillation recurrence was comparable regardless of the occurrence of a VR.

Exercise-induced ventricular tachycardia in a case with hypertrophic cardiomyopathy taking cibenzoline.

We report a 17-year-old woman with hypertrophic cardiomyopathy (HCM) successfully resuscitated from ventricular fibrillation while taking cibenzoline. During exercise-stress testing before implanting an implantable cardioverter-defibrillator, ventricular tachycardia was induced and thought to be a proarrhythmia due to the use-dependent effect of the Na channel blockade with cibenzoline. In patients with arrhythmogenic substrates such as HCM, it is critical to pay attention to the proarrhythmic effects of class I antiarrhythmic drugs while increasing heart rate.

Torsade de pointes induced by intravenous amiodarone therapy accompanied by marked augmentation of the transmural dispersion of repolarization in a patient with tachycardia-induced-cardiomyopathy.

We report a 77-year-old human on renal dialysis for end-stage renal disease with heart failure and atrial fibrillation (AF) complicated by a high ventricular frequency. The underlying disease was thought as tachycardia-induced-cardiomyopathy. Intravenous infusion of amiodarone was initiated, and direct current cardioversion succeeded in converting AF to sinus rhythm. Then, excessive increases in the QT and Tpeak-Tend (Tp-e) intervals were seen and hypokalemia induced by hemodialysis led to the development of numerous episodes of torsades de pointes (TdP). Magnesium repletion was effective in preventing TdP, while Tp-e intervals returned to the previous values 2 days after the discontinuation of amiodarone.