Effect of Empagliflozin Versus Placebo on Body Fluid Balance in Patients With Acute Myocardial Infarction and Type 2 Diabetes Mellitus: Subgroup Analysis of the EMBODY Trial.

BACKGROUND: The development of heart failure is associated with fluid balance, including that of extracellular water (ECW) and intracellular water (ICW). This study determined whether sodium-glucose cotransporter 2 inhibitors affect fluid balance and improve heart failure in patients after acute myocardial infarction. METHODS AND RESULTS: EMBODY was a prospective, randomized, double-blinded, placebo-controlled trial of Japanese patients with acute myocardial infarction and type 2 diabetes. Overall, 55 patients who underwent bioelectrical impedance analysis were randomized to receive once daily 10 mg empagliflozin or placebo 2 weeks after acute myocardial infarction onset. We investigated the time course of body fluid balance measured using the bioelectrical impedance analysis device, InBody. The primary end points were changes in body fluid balance from weeks 0 to 24. Changes between baseline and week 24 in the empagliflozin and placebo groups were -0.21 L (P = .127) and +0.40 L (P = .001) in ECW (P = .001) and -0.23 L (P = .264) and +0.74 L (P < .001) in ICW (P < .001), respectively. In a stratified analysis, the rise in ECW and ICW was significantly attenuated in the empagliflozin group in contrast to the placebo group in participants with a body mass index of 25 or higher but not in those with a body mass index of less than 25. CONCLUSIONS: Early sodium-glucose cotransporter 2 inhibitor administration may attenuate changes in ECW and ICW.

Possibility of steroid therapy without pacemaker implantation in patients with sarcoidosis presenting atrioventricular block.

Atrioventricular Block (AVB) is one of the common manifestations in cardiac sarcoidosis (CS). Although pacemaker implantation is generally recommended in patients with CS complicated by symptomatic AVB, some case reports have shown that they can be managed by steroid therapy without pacemaker implantation. The aim of this study was to evaluate the feasibility and effectiveness of steroid therapy without pacemaker implantation in patients with CS complicated by symptomatic AVB. We performed medical record review of consecutive ten CS patients who admitted Nippon Medical School Hospital for symptomatic second or third degree AVB between April 2015 and March 2021. Of the studied population, steroid therapy before pacemaker implantation was feasible in three patients with second degree AVB. Two of them showed subsequent recovery of atrioventricular conduction to 1:1, and they were managed by steroid therapy without pacemaker. The remaining one patient showed no improvement of atrioventricular conduction and required pacemaker implantation. Seven patients with third degree AVB required device implantation (pacemaker; n = 7, cardiac resynchronization therapy defibrillator; n = 1) before steroid therapy mainly because of hemodynamic instability. Steroid therapy without pacemaker implantation might be feasible, and possibly be effective in patients with CS presenting second degree AVB. However, the feasibility is limited in patients with third degree AVB.

Characteristics of patients with atrial flutter and spontaneous 1:1 atrioventricular conduction with and without anti-arrhythmic drug treatment.

Atrial flutter (AFL) is a large reentrant circuit located in the right atrium. Anti-arrhythmic drugs (AADs) can provoke AFL with 1:1 atrioventricular conduction (AVC) to cause hemodynamic collapse. We elucidated the characteristics of patients with AFL exhibiting spontaneous 1:1 AVC. Fifteen patients (1:1 AFL group; 11 males, 52.4 ± 13.7 years old) who documented AFL with 1:1 AVC were enrolled and compared to 153 patients without 1:1 AVC (Control group; 137 males, 68.9 ± 11.2 years old). AFL cycle length during maximum AVC was significantly longer in the 1:1 AFL group than in the control group (274.7 ± 37.0 vs. 216.2 ± 25.6 ms, p < 0.001). Among 1:1 AVC group, 9 patients had AADs, and AFL cycle length was significantly longer during 1:1 AVC as compared with 2:1 AVC documented the other day (284.4 ± 41.3 vs. 233.3 ± 26.0 ms, p < 0.001), suggesting enhancement effect of the AADs during 1:1 AVC. Remaining 6 patients who did not take AADs, 2 patients showed enlargement of the tricuspid annulus and 3 patients developed 1:1 AVC during exercise. Multivariate analysis revealed that younger age and the use of AADs was independent risk factors for the development of 1:1 AFL group. Prolonged AFL cycle length associated with the class Ia/Ic AAD use, slower heart rate during sinus rhythm and younger age were important risk factors for the development of 1:1 AVC during AFL.

Total activation mapping in a patient with an epicardial accessory pathway.

A 42-year-old man was admitted for recurrent atrioventricular reciprocating tachycardia. We performed a total activation mapping, which included a range from the ventricular to atrial waves during right ventricular pacing. The mapping revealed a delayed ventriculoatrial conduction on the left lateral wall. We performed ablation within the coronary sinus, and the ventriculoatrial conduction was lost. By widening the range, we could easily visualize the ventriculoatrial conduction through the accessory pathway. This mapping showed that the conduction in the area of the accessory pathway was delayed, and it was easy to estimate that the conduction pathway included the coronary sinus.

Ambulatory electrocardiographic markers predict serious cardiac events in patients with chronic kidney disease: The Japanese Noninvasive Electrocardiographic Risk Stratification of Sudden Cardiac Death in Chronic Kidney Disease (JANIES-CKD) study.

BACKGROUND: Noninvasive electrocardiographic markers (NIEMs) are promising arrhythmic risk stratification tools for assessing the risk of sudden cardiac death. However, little is known about their utility in patients with chronic kidney disease (CKD) and organic heart disease. This study aimed to determine whether NIEMs can predict cardiac events in patients with CKD and structural heart disease (CKD-SHD). METHODS: We prospectively analyzed 183 CKD-SHD patients (median age, 69 years [interquartile range, 61-77 years]) who underwent 24-h ambulatory electrocardiographic monitoring and assessed the worst values for ambulatory-based late potentials (w-LPs), heart rate turbulence, and nonsustained ventricular tachycardia (NSVT). The primary endpoint was the occurrence of documented lethal ventricular tachyarrhythmias (ventricular fibrillation or sustained ventricular tachycardia) or cardiac death. The secondary endpoint was admission for cardiovascular causes. RESULTS: Thirteen patients reached the primary endpoint during a follow-up period of 24 ± 11 months. Cox univariate regression analysis showed that existence of w-LPs (hazard ratio [HR] = 6.04, 95% confidence interval [CI]: 1.4-22.3, p = .007) and NSVT [HR = 8.72, 95% CI: 2.8-26.5: p < .001] was significantly associated with the primary endpoint. Kaplan-Meier analysis demonstrated that the combination of w-LPs and NSVT resulted in a lower event-free survival rate than did other NIEMs (p < .0001). No NIEM was useful in predicting the secondary endpoint, although the left ventricular mass index was correlated with the secondary endpoint. CONCLUSION: The combination of w-LPs and NSVT was a significant risk factor for lethal ventricular tachyarrhythmias and cardiac death in CKD-SHD patients.

Localization of Late Gadolinium Enhancement and Its Association with Ventricular Tachycardia in Patients with Cardiac Sarcoidosis.

Sustained ventricular tachycardia (sVT), leading to sudden cardiac death, is one of the common manifestations in cardiac sarcoidosis (CS). Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been reported to be associated with sVT, the relationships of its localization to sVT have not been fully evaluated.To evaluate the localization of LGE and its relationships to sVT in patients with CS, we reviewed medical record of consecutive 31 patients with CS who underwent CMR. The localization of LGE was divided into four categories: Left ventricular (LV) septum, LV free wall, right ventricular (RV) septum, and RV free wall. We investigated the association of sVT with localization of LGE and other parameters including serum biomarkers LV ejection fraction on echocardiography and Fluorine-18-fluorodeoxyglucose (FDG) accumulation on positron emission tomography (PET) -CT.Of the studied population, 8 patients (25.8%) were known to present with sVT among 31 CS patients. LGE was observed in the RV free wall in 6 patients with sVT, whereas it was in 5 patients without sVT (75.0% versus 21.7%, P = 0.022). Univariate analysis showed that only LGE in the RV free wall was associated with sVT (odds ratio [OR]: 10.80; 95% confidence interval [CI]: 1.64-70.93, P = 0.013).LGE in the RV free wall was associated with sVT in patients with CS.

Efficacy of antitachycardia pacing for electrical storms in patients with implantable defibrillators.

INTRODUCTION: Although antitachycardia pacing (ATP) is effective in terminating ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators (ICDs), the efficacy of ATP during an electrical storm (ES) and the positive impact on all-cause mortality have not been fully elucidated. METHODS AND RESULTS: From 2010 to 2012, 1570 patients who underwent ICD implantation in 48 ICD centers in Japan were enrolled in the study and prospectively followed up. Patients with long QT syndrome, Brugada syndrome, and idiopathic ventricular fibrillation were excluded. The prevalence of shocks during ESs and impact on the all-cause mortality were evaluated. During a median follow-up of 28 months, there were 127 ESs in 84 patients. Of those 127 ESs, 80 ESs (63%) in 37 patients were treated by only ATP and the remaining 47 ESs in 47 patients required at least one shock. The lower ventricular rate of the initial arrhythmia during ES (odds ratio [OR]: 1.02 per unit; 95% confidence interval [CI]: 1.00-1.04; p = .02) and narrower QRS complex (OR: 1.03 per unit; 95% CI: 1.01-1.06; p < .01) were the independent predictors of ATP success during the ES. The patients treated with ATP alone tended to have lower all-cause mortality compared to those that required shocks during the ES (log-rank p = .10). CONCLUSIONS: ATP was effective in patients suffering from ESs as it avoided painful shocks in more than half of the cases. Patients who received only ATP during ES tended to have lower mortality compared to those who received the shock.

Prognostic impact of newly detected atrial fibrillation in patients with hypertrophic cardiomyopathy following cardiac implantable electronic device implantation.

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). The present study aimed to investigate the incidence and prognostic impact of newly detected AF after cardiac implantable electronic device (CIED) implantation with HCM patients. Fifty-six patients (33 men, age 57 ± 17 years) with HCM who underwent CIED implantations with no previous history of AF at the time of implantation (ICD n = 46, Pacemaker n = 10) were retrospectively enrolled. During 5.7 ± 3.6 years of follow-up, AF was newly detected in 20 (36%) of 56 patients after the CIED implantation (AF group) and the rest of the patients had no newly detected AF (non-AF group). The presence of mitral regurgitation (HR 8.49; 95% CI 2.29-30.6 P < 0.01) and concomitant NYHA II-IV (HR 3.37; 95% CI 1.30-8.86 P = 0.01) were the independent predictors of newly detected AF. During the follow-up, all patients in the AF group started anticoagulation mean 21 days after detection of AF, and none had a stroke during the follow-up period. The rate of appropriate ICD therapy (log-rank P = 0.95), inappropriate ICD therapy (log-rank P = 0.78), and all-cause death (log-rank P = 0.23) were similar between the two groups. However, the incidence of hospitalizations due to heart failure was higher in the AF group (55% vs. 6% log-rank P < 0.01). In conclusion, the incidence of newly detected AF after CIED implantations in HCM patients was high. The newly detected AF was associated with worsening heart failure and careful follow-up is recommended.

Differential diagnosis between LQT1 and LQT2 by QT/RR relationships using 24-hour Holter monitoring: A multicenter cross-sectional study.

BACKGROUND: The clinical course and therapeutic strategies in the congenital long QT syndrome (LQTS) are genotype-specific. However, accurate estimation of LQTS genotype is often difficult from the standard 12-lead ECG. OBJECTIVES: This study aims to evaluate the utility of QT/RR slope analysis by the 24-hour Holter monitoring for differential diagnosis of LQTS genotype between LQT1 and LQT2. METHODS: This cross-sectional study enrolled 54 genetically identified LQTS patients (29 LQT1 and 25 LQT2) recruited from three medical institutions. The QT-apex (QTa) interval and the QT-end (QTe) interval at each 15-second were plotted against the RR intervals, and the linear regression (QTa/RR and QTe/RR slopes, respectively) was calculated from the entire 24-hour and separately during the day or night-time periods of the Holter recordings. RESULTS: The QTe/RR and QTa/RR slopes at the entire 24-hour were significantly steeper in LQT2 compared to those in LQT1 patients (0.262 ± 0.063 vs. 0.204 ± 0.055, p = .0007; 0.233 ± 0.052 vs. 0.181 ± 0.040, p = .0002, respectively). The QTe interval was significantly longer, and QTe/RR and QTa/RR slopes at daytime were significantly steeper in LQT2 than in LQT1 patients. The receiver operating curve analysis revealed that the QTa/RR slope of 0.211 at the entire 24-hour Holter was the best cutoff value for differential diagnosis between LQT1 and LQT2 (sensitivity: 80.0%, specificity: 75.0%, and area under curve: 0.804 [95%CI = 0.68-0.93]). CONCLUSION: The continuous 24-hour QT/RR analysis using the Holter monitoring may be useful to predict the genotype of congenital LQTS, particularly for LQT1 and LQT2.

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial.

BACKGROUND: Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium-glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity. METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and type 2 diabetes mellitus (T2DM) in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency-to-high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT. RESULTS: Overall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were + 11.6 and + 9.1 ms in the empagliflozin (P = 0.02) and placebo groups (P = 0.06), respectively. Change in LF/HF ratio was - 0.57 and - 0.17 in the empagliflozin (P = 0.01) and placebo groups (P = 0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P = 0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed. CONCLUSIONS: This is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2DM and AMI. Early SGLT2 inhibitor administration in AMI patients with T2DM might be effective in improving cardiac nerve activity without any adverse events. TRIAL REGISTRATION: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442 .

Improved Risk Stratification of Patients With Brugada Syndrome by the New Japanese Circulation Society Guideline　- A Multicenter Validation Study.

BACKGROUND: The new guideline (NG) published by the Japanese Circulation Society (JCS) places emphasis on previous arrhythmic syncope and inducibility of ventricular fibrillation (VF) by ≤2 extrastimuli during programmed electrical stimulation (PES) for deciding the indication of an implantable cardioverter-defibrillator in patients with Brugada syndrome (BrS). This study evaluated the usefulness of the NG and compared it with the former guideline (FG) for risk stratification of patients with BrS.Methods and Results:This was a multicenter (7 Japanese hospitals) retrospective study involving 234 patients with BrS who underwent PES at baseline (226 males; mean age at diagnosis: 44.9±13.4 years). At diagnosis, 46 patients (20%) had previous VF, 100 patients (43%) had previous syncope, and 88 patients (37%) were asymptomatic. We evaluated the difference in the incidence of VF in each indication according to the new and FGs. During the follow-up period (mean: 6.9±5.2 years), the incidence of VF was higher in patients with Class IIa indication according to the NG (NG: 16/45 patients [35.6%] vs. FG: 16/104 patients [15.4%]), while the incidence of VF in patients with other than class I or IIa indication was similarly low in both guidelines (NG: 2/143 patients [1.4%] vs. FG: 2/84 patients [2.4%]). CONCLUSIONS: This study validated the usefulness of the NG for risk stratification of BrS patients.

Detection of arrhythmogenic substrate within QRS complex in patients with cardiac sarcoidosis using wavelet-transformed ECG.

Signal-averaged electrocardiography (SAECG) has been known to be useful for prediction of lethal ventricular arrhythmias (VA). However, this technique has limitations in patients with intraventricular conduction disturbance (IVCD), which is common in cardiac sarcoidosis (CS). Meanwhile, wavelet-transformed ECG (WTECG) has been reported to be useful for detecting arrhythmogenic substrate hidden within QRS complex. The objective of this study was to assess the utility of WTECG for detecting arrhythmogenic substrate in patients with CS. Forty-four CS patients including 18 patients with VA were retrospectively investigated. The parameters on the signal-averaged electrocardiography (SAECG) and the power of frequency components on WTECG were compared between VA group and non-VA group. Eighteen patients have VA (VT: n = 17, VF: n = 1). LP were detected in 17 in VA group and 24 in non-VA group. WTECG showed that high-frequency components (HFC; 80-150 Hz) were developed in VA group. Peak power value at 150 Hz (P150) was significantly higher in VA group than that in non-VA group (442.9 ± 160.2 vs 316.7 ± 100.8, p = 0.006). The receiver operating characteristic (ROC) curve analysis showed an optimal cutoff point of 336 of P150 for detecting patients with VA, with 82.4% sensitivity, 61.5% specificity, and area under the curve of 0.74 (95% confidence interval [CI] 0.59-0.89). WTECG may be useful for detecting CS patients who are prone to VA.

Differential Effectiveness of Landiolol Between Atrial Fibrillation and Atrial Flutter/Atrial Tachycardia Patients With Left Ventricular Dysfunction.

BACKGROUND: Landiolol, an ultra-short acting ß1-selective blocker, is more effective for controlling the heart rate (HR) than digoxin in patients with atrial tachyarrhythmias and left ventricular (LV) dysfunction. The impact of the type of atrial tachyarrhythmias on the effectiveness of landiolol is uncertain. We evaluated the efficacy and safety of landiolol on tachycardiac atrial fibrillation (AF) and tachycardiac atrial flutter/atrial tachycardia (AFl/AT) in patients with reduced LV function. Methods and Results: Seventy-seven patients treated with landiolol were retrospectively analyzed. There were no significant differences in the baseline characteristics between the AF group (n=65) and AFl/AT group (n=12). Despite a higher dosage, the %change in HR from baseline to 12 and 24 h was only -10.2±12.7% and -16.1±19.4% in the AFl/AT group, while it was -28.3±13.2% and -31.3±11.3% in the AF group (P<0.02), respectively. The prevalence of the responders to landiolol treatment was much greater in the AF group than in the AFl/AT group (P<0.001). Alternative treatments such as i.v. amiodarone and electrical cardioversion were required in 83% of the AFl/AT patients. CONCLUSIONS: Landiolol was ineffective in the majority of AFl/AT patients. An alternative management to prevent any worsening of heart failure might be considered in those patients.

Electrocardiographic characteristics in the patients with a persistent left superior vena cava.

A persistent left superior vena cava (PLSVC) is a congenital venous abnormality and is usually asymptomatic and does not cause hemodynamic disturbances. Therefore, it is difficult to identify it by routine examinations in clinical practice. This study aimed to elucidate the electrocardiographic characteristics for the prediction of a PLSVC. Twelve patients (9 males, 56.2 ± 18.3 years) who were diagnosed with a PLSVC were enrolled. The electrocardiographic parameters, including the P-wave duration, axis, and morphology of the P waves, were automatically measured and compared to 150 controls (77 males, 57.3 ± 14.6 years). There were no significant differences in the P-wave duration. Negative or positive/negative P waves in lead III predicted a PLSVC with a sensitivity of 100% and specificity of 81%. The P-wave axis in PLSVC exhibited a significant leftward deviation as compared to the controls (14.8 ± 21.1 vs. 54.0 ± 17.4°, p < 0.001). A receiver operating characteristic curve analysis of the P-wave axis for predicting a PLSVC exhibited an area under curve of 0.93 [CI 95% (0.87-0.98), p < 0.001), and identified a P-wave axis of less than 37.5° to have a 92% sensitivity and 83% specificity in predicting a PLSVC. A negative or positive/negative P-wave morphology in lead III was a useful finding for suggesting the presence of a PLSVC.

Validation of wearable textile electrodes for ECG monitoring.

A highly conductive textile was woven from nano-fibers coated with the PEDOT-PSS polymer. The aim of this study was to assess the usefulness of textile electrodes for ECG recording as a smart garment. Electrode textile pads and lead wires were sewn to the lining of sportswear and their tolerability to repeated washings were tested up to 150 times. The electrical conductivity of the textile electrode remained functional for up to 50 machine washes. To assess the level of motion artifacts or noise during the daily monitoring of ECG, a single lead ECG with conventional or textile electrodes was recorded during supine rest, seated rest, upright trunk rotation (i.e., twisting), and stepping movement in 66 healthy adults. A Holter system was used for data storage and analysis. ECG patterns of P, QRS, and T waves were comparable between the conventional and textile electrodes. However, the signal-to-artifact-and/or-noise ratio (SAR) during twisting was larger in the textile electrodes than in the conventional electrodes. No skin irritation was seen in the textile electrodes. The single lead textile electrodes embedded in an inner garment were usable for continuous and/or repeated ECG monitoring in daily life except during vigorous trunk movement.

Blanking Period Phenomenon After a Second Atrial Fibrillation Ablation Session: The Application and Factors Related to It.

INTRODUCTION: The concept of a 3-month blanking period is widely accepted after the first radiofrequency catheter ablation (RFCA) session for atrial fibrillation (AF). We sought to investigate whether this phenomenon was also observed after a 2nd session, and which factors were related to it. METHODS AND RESULTS: We conducted a prospective observational study including all AF patients who underwent RFCA since 2010. The patients who underwent a second RFCA were followed without any antiarrhythmic drugs. Their clinical background, laboratory data, echocardiographic parameters, ablation procedures, and arrhythmia recurrences were analyzed. Recurrences were classified into early period recurrences (EPRs) and late period recurrences (LPRs) recorded within and after the first 3 months postablation, respectively. Among 925 patients who underwent an initial AF ablation, 2nd sessions were performed in 250 patients, and EPRs and LPRs occurred in 53 (21.2%) and 54 (21.6%) patients, respectively. Although EPRs were an independent predictor of LPRs (hazard ratio [HR], 8.01; 95% confidence interval [CI] 4.03-15.93, P < 0.001), 20 of the patients with EPRs (37.7%) did not experience LPRs, supporting the concept of a blanking period. Among 53 patients with EPRs, the E/E' ratio on echocardiography (HR, 1.156; 95% CI 1.00-1.33, P = 0.04) was an independent predictor of LPRs, while other parameters including the maximum serum C-reactive protein level after the session and the ablation procedure details were not. CONCLUSION: A 3-month blanking period was also applicable after the 2nd AF ablation session. This phenomenon was related to a lower left atrial pressure demonstrated by the E/E' ratio.