Diagnosis and Management of Paroxysmal Supraventricular Tachycardia.

Importance: Paroxysmal supraventricular tachycardia (PSVT), defined as tachyarrhythmias that originate from or conduct through the atria or atrioventricular node with abrupt onset, affects 168 to 332 per 100 000 individuals. Untreated PSVT is associated with adverse outcomes including high symptom burden and tachycardia-mediated cardiomyopathy. Observations: Approximately 50% of patients with PSVT are aged 45 to 64 years and 67.5% are female. Most common symptoms include palpitations (86%), chest discomfort (47%), and dyspnea (38%). Patients may rarely develop tachycardia-mediated cardiomyopathy (1%) due to PSVT. Diagnosis is made on electrocardiogram during an arrhythmic event or using ambulatory monitoring. First-line acute therapy for hemodynamically stable patients includes vagal maneuvers such as the modified Valsalva maneuver (43% effective) and intravenous adenosine (91% effective). Emergent cardioversion is recommended for patients who are hemodynamically unstable. Catheter ablation is safe, highly effective, and recommended as first-line therapy to prevent recurrence of PSVT. Meta-analysis of observational studies shows single catheter ablation procedure success rates of 94.3% to 98.5%. Evidence is limited for the effectiveness of long-term pharmacotherapy to prevent PSVT. Nonetheless, guidelines recommend therapies including calcium channel blockers, ß-blockers, and antiarrhythmic agents as management options. Conclusion and Relevance: Paroxysmal SVT affects both adult and pediatric populations and is generally a benign condition. Catheter ablation is the most effective therapy to prevent recurrent PSVT. Pharmacotherapy is an important component of acute and long-term management of PSVT.

Shenfu Administration Improves Cardiac Fibrosis in Rats With Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation.

OBJECTIVE: Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A2a receptor (A2aR) in rats with myocardial ischemia-reperfusion (MI/R). METHODS: Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5 mL/kg in the SFI group; 15 mg/kg nicorandil in the A2R agonist group; and 5 mL/kg SFI plus 5 mg/kg MSX-3 in the SFI + A2aR antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of A2aR, collagen Ⅰ, collagen Ⅲ, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured. RESULTS: Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased (p < 0.05). Additionally, the levels of collagen Ⅰ, collagen Ⅲ, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (p<0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between A2aR and collagen I and collagen III was found (p = 0.00). CONCLUSION: SFI activated the A2aR to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI.

Comparing methods of adenosine administration in paroxysmal supraventricular tachycardia: a pilot randomized controlled trial.

BACKGROUND: Intravenous adenosine is the recommended treatment for paroxysmal supraventricular tachycardia (PSVT). There is no official recommended method of giving adenosine. We compared the success rates between a standard and alternative method of first dose intravenous adenosine in PSVT. METHODS: A pilot parallel randomized controlled study was conducted in the emergency department of a tertiary care hospital. Eligible patients were stable PSVT adult patients. We used block randomization and divided them into two groups, the standard method (double syringe technique of 6 mg of adenosine), and the alternative method (similar to the standard method, then immediately followed by elevating the arm to 90° perpendicular to a horizontal plane for 10 s). The primary outcome was the success rate of electrocardiogram (ECG) response which demonstrated termination of PSVT (at least two-fold of the RR-interval widening or sinus rhythm conversion). Secondary outcomes were complications within one minute after the injection. RESULTS: We allocated 15 patients in each group and analyzed them as intention-to-treat. The success rate was 86.7% in the alternative group and 80% in the standard group (risk difference 6.7%, 95% confidence interval - 19.9 to 33.2%, P 1.00). Complications within one minute after adenosine injection were also similar in both groups, 14 of 15 patients (93%) in each group had no complications, without significant difference. CONCLUSIONS: No evidence of the difference between alternative and standard methods occurred, in terms of the success rate of ECG response and complications within one minute after adenosine injection. The standard method of adenosine injection is a safe, easy-to-administer, and widely available treatment for PSVT. TRIAL REGISTRATION: TCTR20200609001.

Role of chronic continuous intravenous lidocaine in the clinical management of patients with malignant type 3 long QT syndrome.

BACKGROUND: Type 3 long QT syndrome (LQT3) is caused by pathogenic, gain-of-function variants in SCN5A leading to a prolonged action potential, ventricular ectopy, and torsades de pointes. Treatment options include pharmacotherapy, cardiac denervation, and/or device therapy. Rarely, patients with malignant LQT3 require cardiac transplantation. OBJECTIVE: The purpose of this study was to evaluate the role of chronic continuous intravenous (IV) lidocaine as a therapeutic option for select patients with LQT3 refractory to standard therapy. METHODS: We performed a retrospective review of patients evaluated and treated at Mayo Clinic and identified 4 of 161 patients with LQT3 (2.5%) who were refractory to standard therapies and therefore treated with IV lidocaine. RESULTS: There were 4 patients (2 female [50%]). The median age at first IV lidocaine infusion was 2 months (interquartile range 1.5-4.8 months), and the median cumulative duration on IV lidocaine was 11.5 months (interquartile range 8.7-17.8 months). The main indication for IV lidocaine in all patients was persistent ventricular arrhythmias. Before IV lidocaine, all patients received an implantable cardioverter-defibrillator, and while on intermittent IV lidocaine, all patients underwent bilateral cardiac sympathetic denervation. Additionally, 2 (50%) patients had cardiac ablation for premature ventricular complexes. In all patients, lidocaine infusion resulted in a significant reduction of LQT3-triggered cardiac events. The main side effects of IV lidocaine observed were dizziness (n = 2, 50%) and seizures (n = 2, 50%). During follow-up, 3 of 4 (75%) patients underwent orthotopic cardiac transplantation. The remaining patient continues to receive IV lidocaine bolus for rescue as needed. CONCLUSION: For patients with LQT3 who are refractory to standard treatment, chronic IV lidocaine infusion can be used as a potential "bridge to transplant."

Wide complex tachycardia in dialysis patients is not always hyperkalemia.

BACKGROUND: Flecainide is a commonly used IC antiarrhythmic. Clinical presentations of Flecainide toxicity are not commonly described. CASE REPORT: A 62 year old man on dialysis presented for evaluation of outpatient bradycardia and hypotension. In the ED, patient had wide-complex rhythm with heart rates ranging from 76 to 127. The previous day, Flecainide and Metoprolol were discontinued and patient was dialyzed and discharged. The patient was treated empirically for possible hyperkalemia. No significant change in ECG was noted with administration of calcium. Sodium bicarbonate produced questionable benefit. Potassium level was 4.6 mmol/L. Cardiac rhythm fluctuated between sinus rhythm and wide complex tachycardia in the ED & ICU. Flecainide level was 2.1 µg/ml (normal <1 µg/ml). Toxicity developed despite previous discontinuation and dialysis prior to presentation because of Flecainide's large volume of distribution and lipopholicity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although Flecainide toxicity is uncommon, it has a high mortality rate, requiring early identification and treatment. Flecainide toxicity can develop in patients with hepatic or renal insufficiency, and can manifest with ventricular tachycardia or bradycardia. If suspicion of Flecainide toxicity arises, lidocaine and procainamide should be avoided to prevent further sodium channel blockade. Absence of response to calcium for a very wide complex QRS should raise clinicians' suspicion that WCT is not due to hyperkalemia, emphasizing the importance of reviewing patients' home medications. Sodium bicarbonate should be administered early to treat widened QRS. Amiodarone, intralipid emulsion therapy and ECMO may be considered in severe cases.

Benefits of prescribing low-dose digoxin in atrial fibrillation.

INTRODUCTION: The role of digoxin (cardiac glycoside) in controlling the heart rate (HR) for the treatment of atrial fibrillation (AF) patients has not been explored in depth. METHODS: To contribute to the limited data, our team conducted retrospective analysis of the clinical records of 1444 AF patients. We divided the AF patients into two groups, wherein group 1 patients were treated with beta-blockers (BB), low-dose digoxin, and an anticoagulant (vitamin K antagonist/factor-IIa inhibitor/factor-Xa inhibitor), and group 2 patients were treated with just BB and an anticoagulant. Our objectives were to compare the impact of combination therapy of BB and digoxin on the resting HR in patients with permanent AF and the patients' quality of life (QOL) at periodic intervals. RESULTS: The findings of our study showed a better control of the resting HR rate (<110bpm) and an improved QOL among the group 1 patients when compared with group 2 patients. CONCLUSION: Our findings are indicative of the favorable clinical outcomes that resulted from the addition of a low-dose of digoxin to the AF treatment regimen. However, larger studies/trials elucidating the outcomes of AF patients treated with the dual rate control therapy are required, to clarify the role of digoxin, guide the choice of agents, and standardize the AF treatment protocol.

Characterization of Preclinical Pharmacokinetic Properties and Prediction of Human PK Using a Physiologically Based Pharmacokinetic Model for a Novel Anti-Arrhythmic Agent Sulcardine Sulfate.

PURPOSE: Sulcardine sulfate (Sul) is a novel antiarrhythmic agent with promising pharmacological properties, which is currently being evaluated in several clinical trials as an oral formulation. To meet the medication needs of patients with acute conditions, the injection formulation of Sul has been developed. The objective of this study was to systemically investigate the pharmacokinetic profiles of Sul after intravenous infusion. METHODS: This research included the plasma protein binding and metabolic stability studies in vitro, plasma pharmacokinetics, biodistribution, excretion studies in animals, and the prediction of the clinical PK of Sul injection using a physiologically based pharmacokinetics (PBPK) model. RESULTS: The metabolic stability was similarly in dogs and humans but lower in rats. The plasma protein binding rates showed a concentration-dependent manner and species differences. The pharmacokinetic behavior after intravenous administration was linear in rats within the dose range of 30-90 mg/kg, but nonlinear in dogs within 30-60 mg/kg. Sul could be rapidly and widely distributed in multiple tissues after intravenous administration. About 12% of the parent compound were excreted via the urine and only a small fraction via bile and feces,and eight metabolites were found and identified in the rat excretion. The PBPK models were developed and simulated the observed PK date well in both rats and dogs. The PBPK model refined with human data predicted the PK characteristics of the first intravenous infusion of Sul in human. CONCLUSIONS: Our study systematically explored the pharmacokinetic characteristics of Sul and successfully developed the PBPK model to predict of its clinical PK.

Antiarrhythmic drug therapy after catheter ablation for atrial fibrillation-Insights from the German Ablation Registry.

Data on the optimal treatment strategy for antiarrhythmic drug therapy (AAD) after catheter ablation for atrial fibrillation (AF) are inconsistent. The present study investigates whether postinterventional AAD leads to an improved long-term outcome. Patients from the prospective German Ablation Registry (n = 3275) discharged with or without AAD after catheter ablation for AF were compared regarding the rates of recurrences, reablations and cardiovascular events as well as patient reported outcomes during 12 months follow-up. In patients with paroxysmal AF (n = 2138) the recurrence rate did not differ when discharged with (n = 1051) or without (n = 1087) AAD (adjusted odds ratio (OR) 1.13, 95% confidence interval (CI) [0.95-1.35]). The reablation rate was higher and reduced treatment satisfaction was reported more often in those discharged with AAD (reablation: OR 1.30, 95% CI [1.05-1.61]; reduced treatment satisfaction: OR 1.76, 95% CI [1.20-2.58]). Similar rates of recurrences, reablations and treatment satisfaction were found in patients with persistent AF (n = 1137) discharged with (n = 641) or without (n = 496) AAD (recurrence: OR 1.22, 95% CI [0.95-1.56]; reablation: OR 1.21, 95% CI [0.91-1.61]; treatment satisfaction: OR 1.24, 95% CI [0.74-2.08]). The incidence of cardiovascular events and mortality did not differ at follow-up in patients discharged with or without AAD. In conclusion, the rates of recurrences, cardiovascular events and mortality did not differ between patients discharged with or without AAD after AF catheter ablation. However, AAD should be considered carefully in patients with paroxysmal AF, in whom it was associated with a higher reablation rate and reduced treatment satisfaction. Clinical trial registration: The trial has been registered under the number NCT01197638.

dST-Tiso Interval, a Novel Electrocardiographic Marker of Ventricular Arrhythmia Inducibility in Individuals With Ajmaline-Induced Brugada Type I Pattern.

The aim of this study was to investigate the reliability of a novel electrocardiographic (ECG) marker in predicting ventricular arrhythmia (VA) inducibility in individuals with drug-induced Brugada syndrome (BrS) type I pattern. Consecutive patients with drug-induced type I BrS pattern underwent programmed ventricular stimulation (PVS) and, according to their response, were divided into 2 groups. Clinical characteristics and 12-lead ECG intervals before and after ajmaline infusion were compared between the 2 groups. A novel ECG marker named dST-Tiso interval consisting in the interval between the onset of the coved ST-segment elevation and its termination at the isoelectric line was also evaluated. Our cohort included 76 individuals (median age 44 years, 75% male). Twenty-five (32.9%) had VA inducibility requiring defibrillation. As compared with not inducible subjects, those with VA inducibility were more frequently male (92% vs 65%, p = 0.013), had longer PQ interval (basal: 172 vs 152 ms, p = 0.033; after ajmaline: 216 vs 200 ms, p = 0.040), higher J peak (0.6 vs 0.5 mV, p = 0.006) and longer dST-Tiso (360 vs 240 ms, p < 0.001). The dST-Tiso showed a C-statistics of 0.90 (95% confidence interval: 0.82 to 0.99) and an adjusted odds ratio for VA of 1.03 (1.01 to 1.04, p < 0.001). A dST-Tiso interval >300 ms yielded a sensitivity of 92.0%, a specificity of 90.2%, positive and negative predictive values of 82.1% and 95.8%. In conclusion, the dST-Tiso interval is a powerful predictor of VA inducibility in drug-induced BrS type I pattern. External validation is needed, but this marker might be useful in the clinical counseling process of these individuals before invasive PVS.

Bedside Electrophysiological Study Using a Temporary Pacemaker May Predict Recurrence of Atrioventricular Block After Transcatheter Aortic Valve Replacement.

High-degree atrioventricular block (HAVB) or complete heart block (CHB) is a common complication associated with transcatheter aortic valve replacement (TAVR). However, some patients with HAVB/CHB recover with time. The results of electrophysiological studies (EPSs) using permanent pacemaker implantation (PPI) in patients with suspicious HAVB/CHB are considered controversial.This study aimed to evaluate whether HAVB/CHB induction at the bedside using a temporary pacemaker can predict recurrence in patients who had recovered from HAVB/CHB after TAVR.We enrolled a total of 11 patients who had recovered from HAVB/CHB and evaluated their electrophysiology using right ventricular pacing and/or procainamide administration.HAVB/CHB induction was positive. Three patients tested positive for HAVB/CHB, whereas 8 tested negative. The ejection fraction and the interval between HAVB/CHB onset and EPS were found to be significant. HAVB/CHB positive patients underwent PPI. A patient with a balloon-expandable valve tested positive just before recovery of CHB, but tested negative 5 days later and was included in the negative group. The 4 patients who tested negative received a cardiovascular implantable electric device (CIED). We observed HAVB/CHB in 2 patients who had previously tested positive after 3 months. Among those who tested negative, those with CIED had no HAVB/CHB, and others showed neither HAVB/CHB on electrocardiogram nor experienced syncope or sudden death.Our EPS revealed that HAVB/CHB induction may predict HAVB/CHB recurrence after TAVR. Valve type and EPS timing may affect the results.