Cardiac resynchronization therapy (CRT) essentially targets electrical dyssynchrony, one of the key drivers in heart failure (HF). Its efficacy depends on both the quality (QRS morphology) and quantity (QRS duration) of dyssynchrony, requiring individualized patient selection. While drug therapy for HF has a limited effect on this substrate, early implantation of CRT can prevent irreversible remodeling and facilitate optimization of medical therapy. CRT should be recognized as an essential component within a comprehensive strategy for HF management in patients with appropriate indications.

Background: Cardiac resynchronization therapy (CRT) is an effective treatment for chronic heart failure, but dual-site (2V) pacing may not fully eliminate electrical dyssynchrony. Triple-site (3V) pacing, adding an additional left ventricle (LV) pacing site, may enhance CRT outcomes. Objective: This study examines the long-term effects of 2V vs 3V CRT, using temporary pacing to individualize lead placement. Methods: From 2010 to 2016, 92 patients with New York Heart Association (NYHA class II-IV heart failure, left ventricular ejection fraction (LVEF) < 35%, and QRS duration > 120 ms received CRT guided by temporary pacing. Patients underwent invasive pacing studies to measure electrical and hemodynamic improvements between 2V and 3V configurations. Based on QRS narrowing and LV dP/dtmax improvements, 27 patients were assigned to the 3V group and 65 to the 2V group. Clinical outcomes, including the clinical composite score (CCS), NYHA class, QRS duration, heart failure (HF) events, and mortality, were followed up over an average 8.3 years. Results: At 1 year, the 3V group had significantly better CCS outcomes compared with the 2V group (P = .018). Long-term follow-up showed a significantly lower HF event rate in the 3V group (P = .002), although overall mortality did not differ. Multivariate analysis identified 3V pacing as an independent predictor of reduced HF events (hazard ratio [HR] = 0.275; P = .018). Despite shorter battery life in the 3V group, device replacement rates were similar. Conclusion: Temporary pacing-guided 3V CRT provides significant long-term benefits over 2V CRT by reducing HF events. These findings support the necessity of individualized assessment and approach to eliminate electrical dyssynchrony when considering multi-site pacing CRT.

Coronavirus disease 2019 (COVID-19) is associated with cardiovascular complications; however, Takotsubo cardiomyopathy (TCM) with QT prolongation and Torsade de pointes has been reported only rarely. We present a case of TCM after QT prolongation and Torsade de pointes. A 58-year-old woman was admitted because of COVID-19-related pneumonia. Seven days after admission, she developed sudden loss of consciousness without any indication of cardiovascular disease. A monitoring electrocardiogram indicated Torsade de pointes and a prolonged QT interval. Emergency cardiac catheterization revealed TCM. She was treated with favipiravir and steroids, followed by rehabilitation, and her condition improved. To detect asymptomatic TCM, routine electrocardiography screening should be considered for patients with COVID-19.

Abstract Background Cardiac resynchronization therapy (CRT) reduces cardiac electrical dyssyncrhony and improves clinical outcomes in selected symptomatic patients with left ventricular (LV) systolic dysfunction. However, patients after conventional CRT (Bi-V) have residual cardiac electrical dyssynchrony. CRT with multi-site pacing has gained attention to improve short-term outcome refractory to BiV. However, long-term follow up outcome is still uncertain. We evaluated the efficacy of CRT with triple-site ventricular stimulation (Tri-V), involving 2 LV lead in 2 anatomically separated veins and a single RV lead in RV apex for long-term follow up period. Methods Ninety-two consecutive patients with New York Heart Association class II-IV heart failure, LV ejection fraction <0.35, and QRS interval >120ms, who underwent CRT implantation between 2010 and 2016, were enrolled. Acute hemodynamic responses to temporary dual-site and triple-site ventricular pacing were evaluated, and patients were assigned to either the Bi-V or Tri-V group based on the results. The primary endpoint was the HF clinical composite score, which scores patients as improved, unchanged, or worsened. The secondary endpoint included cumulative survival from any cause of death and HF hospitalization. Results Tri-V was successfully implanted in 32 patients. Five patients were excluded during follow-up because of uncaptured pacing in one of the LV leads. One year post-implantation, the clinical composite score significantly improved in 84% of Tri-V patients compared to 57% in the Bi-V group (p=0.026). After a median follow-up of 12.0 years, there was no significant difference about all-cause mortality between Tri-V and Bi-V (p=0.147). However, Tri-V group showed significant lower HF hospitalization (p=0.005) than Bi-V group. The number of battery exchange was not significantly different between Tri-V than Bi-V group (1.4±0.7 vs. 1.2±0.8, p=0.361). Conclusion CRT with Tri-V, characterized by stable lead parameters, appears to offer greater long-term benefits than Bi-V in terms of clinical status without excessive battery exchanges.figure

Abstract Background Cardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure with electrical dyssynchrony. The LV lead position in patients with left bundle branch block is usually recommended at the LV posterolateral to the lateral site, which is the latest electrical activation site. In contrast, the preferable LV lead position in patients who plan to upgrade from conventional RV apical pacing to CRT remains unclear. Purpose This study aimed to identify the preferable LV lead position for upgrading to CRT from conventional RV apical pacing. Methods An electrophysiological study was performed on patients who underwent ablation for atrial fibrillation. The electrode catheters were positioned at the RV apex, LV anterolateral, and LV posterolateral sites via the coronary sinus branches. During RV apical pacing, the activation time from the RV apex to the LV anterolateral and posterolateral sites was measured, and the activation time ratio to QRS duration was calculated. Biventricular pacing from both the RV apex and LV anterolateral or LV posterolateral sites was performed, and the difference in QRS duration and LV dP/dt compared to only the RV apical pacing state was measured. Results We enrolled 37 patients who exhibited anterolateral and posterolateral LV coronary sinus branches. During RV apical pacing, the average activation time ratio to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.89±0.07 vs. 0.71±0.11, P <0.001). The shortening ratio of QRS duration during biventricular pacing compared to baseline RV apical pacing was greater at LV anterolateral site than at the LV posterolateral site (45.7±18.0% vs. 32.0±17.6%, P <0.001). The improvement ratio of LV dP/dt during biventricular pacing was also better from the LV anterolateral site than from the LV posterolateral site (12.7±8.9% vs. 3.7±8.2%, P <0.001). Conclusion LV lead position in patients who plan to upgrade to CRT from conventional RV apical pacing is preferably at the LV anterolateral site.

INTRODUCTION:Cardiac resynchronization therapy (CRT) is well-established for treating symptomatic heart failure with electrical dyssynchrony. The left ventricular (LV) lead position is recommended at LV posterolateral to lateral sites in patients with left bundle branch block; however, its preferred region remains unclear in patients being upgraded from right ventricular (RV) apical pacing to CRT. This study aimed to identify the preferred LV lead position for upgrading conventional RV apical pacing to CRT.METHODS:We used electrode catheters positioned at the RV apex and LV anterolateral and posterolateral sites via the coronary sinus (CS) branches to measure the ratio of activation time to QRS duration from the RV apex to the LV anterolateral and posterolateral sites during RV apical pacing. Simultaneous biventricular pacing was performed at the RV apex and each LV site, and the differences in QRS duration and LV dP/dtmax from those of RV apical pacing were measured.RESULTS:Thirty-seven patients with anterolateral and posterolateral LV CS branches were included. During RV apical pacing, the average ratio of activation time to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.90 ± 0.06 vs. 0.71 ± 0.11, p < .001). The decreasing ratio of QRS duration and the increasing ratio of LV dP/dtmax were higher at the LV anterolateral site than at the posterolateral site (45.7 ± 18.0% vs. 32.0 ± 17.6%, p < .001; 12.7 ± 2.9% vs. 3.7 ± 8.2%, p < .001, respectively) during biventricular pacing compared with RV apical pacing.CONCLUSION:The LV anterolateral site is the preferred LV lead position in patients being upgraded from conventional RV apical pacing to CRT.

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Skeletal muscle mass is reduced in severe heart failure and has a significantly impacts on subsequent outcomes and quality of life. The assessment of pectoralis muscle measures by computed tomography (CT) scan may be predictive of outcomes after left ventricular assist device (LVAD) implantation. Purpose This study aims to assess preoperative pectoralis muscle measures before LVAD implantation to predict early rehospitalization of the patient. Methods We measured the cross-sectional area and mean CT values of the unilateral pectoralis muscle (PHUm: mean Hounsfield unit of pectoralis muscle) by CT scans within 3 months before surgery in patients who underwent HeartMate 3 implantation for the bridge to transplant (BTT) or destination therapy (DT) at our hospital, by August 2022. The cross-sectional area of the unilateral pectoralis muscle was corrected for body surface area (PMI: pectoralis muscle index). The pectoralis muscle was measured by SYNAPSE VINCENT image analysis (Fuji Film) using an axial section of the superior margin of the aortic arch (Figure A). The area under the curve (AUC), sensitivity, and specificity of each index was calculated by receiver operating characteristic (ROC) analysis for the prediction accuracy of PHUm, PMI, and the product of PHUm and PMI in rehospitalization 30, 60, 90 and 180 days from discharge. Results Of reviewed 39 patients who underwent HeartMate 3 implantation, 32 (82%) were male, and 32 (82%) underwent BTT. The median age at LVAD implantation was 52 years (interquartile range [IQR], 42–57). During the follow-up period after discharge (median: 520 days, IQR: 116–707), 19 patients (53%) had unscheduled hospitalizations due to 8 LVAD-related infections, 1 heart failure, 1 cardiac arrhythmia, and 9 other reasons. The median time between discharge and rehospitalization was 70 days (IQR, 31–139). ROC analysis showed that the AUC was particularly high for early rehospitalization within 30 days, with the optimal cutoff of 21.8 Hounsfield unit (HU) for PHUm (sensitivity 0.903, specificity 0.800, AUC 0.884), 6.37 cm2/m2 for PMI (sensitivity 0.806, specificity 0.800, AUC 0.735), and 142.8 for the product of PHUm and PMI (sensitivity 0.903, specificity 1.000, AUC 0.948) (Figure B). Conclusion The product of PHUm and PMI may be a strong predictor of early rehospitalization within 30 days of discharge after LVAD implantation.

Micra (Medtronic, Minneapolis, MN) is a leadless pacemaker implanted percutaneously through a transcatheter system1,2 and is an alternative form of ventricular pacing that may avoid the complications of traditional transvenous pacing systems.3 Compared with the traditional transvenous systems, Micra reportedly reduces the incidence of major complications by approximately 63%.4 Therefore, a leadless pacemaker is preferred for older patients with comorbidities who are at significantly increased risk of transvenous pacing systems complications.

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. (J Cardiac Fail 2022;28:56-64) cotransporter 2 inhibitor.

Background: Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been evaluated recently as a prognostic marker of patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether the sodium-glucose cotransporter 2 (SGLT2) inhibitor affect the improvement of heart failure and PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF). Methods: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of the SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. A total of one hundred and five patients were randomized (1:1) to receive once-daily 10 mg empagliflozin or placebo 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS on baseline, weeks 4, 12 and 24. Results: Overall, 96 patients were included in the subgroup analysis set (64.3±10.9 years, male 80.2%, and 46 in the empagliflozin group and 50 in the placebo group). The empagliflozin group showed significant decreases in body weight, systolic blood pressure, and PVS compared with the placebo group at 24 weeks (-2.2 vs. +0.1 kg, P=0.0007; -6.6 vs. +3.5 mmHg, P=0.003; and -5.1 vs. -0.3%, P=0.0006; respectively). Decreased of PVS, defined as change of PVS < -4.5 % was associated with received empagliflozin (odds ratio, 2.61; 95% confidence interval, 1.11 - 6.15; P=0.028). On the other hand, NT-Pro BNP levels significantly decreased in the empagliflozin group and placebo group (1028.7 to 370.3 pg/ml, P=0.0001 and 1270.6 to 673.7 pg/ml, P=0.006, respectively). Conclusion: Empagliflozin reduced not only body weight but also PVS. These results suggested that early SGLT2 inhibitor administration in patients with AMI, CHF and T2DM could be effective to reduce body weight and PVS.

Cardiac resynchronization therapy (CRT) improves cardiac function by correcting electrical dyssynchrony in patients with symptomatic heart failure (HF). However, current guidelines focus on QRS interval alone with respect to electrical dyssynchrony. We implanted CRT in a patient with a QRS interval of 126 ms with left anterior hemiblock because a temporary pacing study before CRT showed correction of left anterior hemiblock with hemodynamic improvement via pacing at the electrically delayed left anterior site alone.

Introduction: Right ventricular (RV) pacing causes changes in the heart’s electrical and mechanical activation patterns. QRS duration is a useful surrogate marker of electrical dyssynchrony; longer QRS duration during RV pacing indicates poor prognosis. However, the mechanisms underlying longer QRS duration during RV pacing remain unclear; hence, we investigated factors predicting QRS prolongation during RV pacing. Methods and Results: We enrolled 211 patients who underwent catheter ablation for supraventricular tachyarrhythmia and showed no bundle-branch-block. Three-dimensional mapping for QRS duration during RV pacing from the RV outflow to RV apex was performed, and the difference in QRS duration was analyzed. The predisposing factors causing QRS >160 ms during RV apical pacing were also analyzed. QRS durations at baseline and during RV pacing from the RV outflow and at RV apex were 85.0±7.5 ms, 163.7±17.1 ms, and 156.2±16.1 ms, respectively. With respect to QRS duration, there was a significant correlation between RV outflow and RV apical pacing (r=0.658, p<0.001). The difference in QRS duration between RV outflow and apex in each patient was only 12.5±10.4 ms. Logistic multivariable regression analysis identified baseline QRS duration [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.15 to 1.33, p<0.01], interventricular septum thickness (OR 1.20, 95% CI 1.02-1.40, p=0.025), left atrial diameter (OR 1.08, 95% CI 1.01-1.16, p=0.024), and E/e’ (OR 1.23, 95% CI 1.12-1.35, p<0.01) as significant predictors of prolonged QRS duration during RV apical pacing. Conclusion: QRS duration during RV pacing largely depends not on the pacing site, but on underlying structural heart diseases.

AbstractAimsAlthough the reno‐protective effects of sodium–glucose cotransporter 2 inhibitors are known in patients with heart failure or type 2 diabetes mellitus (T2DM), this effect has not been confirmed in patients with acute myocardial infarction (AMI).Methods and resultsThe prospective, multicentre, randomized, double‐blind, placebo‐controlled EMBODY trial investigated patients with AMI and T2DM in Japan. The eligible patients included adults aged 20 years or older, diagnosed with AMI and T2DM, and who could be discharged within 2–12 weeks after the onset of AMI. One hundred and five patients were randomized (1:1) to receive once daily 10 mg empagliflozin or placebo within 2 weeks of AMI onset. In this sub‐analysis, we investigated the time course of renal functional parameters such as serum creatinine levels and estimated glomerular filtration rate (eGFR) from baseline to Weeks 4, 12, and 24. Ninety‐six patients (64 ± 11 years, 78 male) were included in the full analysis (n = 46 and 50 in the empagliflozin and placebo groups, respectively). We used serum creatinine and eGFR as indicators of renal function. In the placebo group, eGFR decreased from 66.14 mL/min/1.73 m2 at baseline to 62.77 mL/min/1.73 m2 by Week 24 (P = 0.023) but remained unchanged in the empagliflozin group (from 64.60 to 64.36 mL/min/1.73 m2, P = 0.843). In the latter group, uric acid improved from 5.8 mg/dL at baseline to 4.9 mg/dL at Week 24 (P < 0.001). In the earlier analysis of 56 patients with eGFR ≥ 60 mL/min/1.73 m2, the eGFR decreased and the serum creatinine increased from baseline to 24 weeks in the placebo group, significantly different to the empagliflozin group (−6.61 vs. +0.22 mL/min/1.73 m2, P = 0.008 and +0.063 vs. −0.001 mg/dL, P = 0.030, respectively). The changes in serum creatinine and eGFR from baseline to Week 24 were significantly correlated with those in uric acid in the placebo group (r = 0.664, P < 0.001 and r = −0.675, P < 0.001, respectively) but not in the empagliflozin group.ConclusionsEmpagliflozin prevented the kidney functional decline in patients with AMI and T2DM, especially those with baseline eGFR ≥ 60 mL/min/1.73 m2. Early administration of sodium–glucose cotransporter 2 inhibitors in these patients is considered desirable for renal protection.

Introduction: There is increasing evidence of the epicardial connection between the right-sided pulmonary vein (PV) carina and right atrium interrupts right-sided PV isolation after circumferential PV ablation in patients with atrial fibrillation. In such cases, carina ablation is often required. This study aimed to assess the utility of the right atrial posterior wall (RAPW) pacing in the detection of the right-sided epicardial connection (EC), evaluate the requirement for additional carina ablation after circumferential pulmonary vein (PV) ablation depending on the presence of EC, and investigate the clinical characteristics including the amount of epicardial adipose tissue (EAT) in patients with ECs. Methods and Results: Forty-one patients scheduled for PV isolation were enrolled. Before ablation, activation mapping of the LA was prospectively performed during pacing from the RAPW. EC was observed in 12 patients (EC group, 29%), whereas no EC was observed in the remaining 29 patients (non-EC group, 71%). For PV isolation, carina ablation was required in addition to circumferential ablation in 7 patients (58%) in the EC group, compared to 2 patients (7%) in the non-EC group (p < 0.003). Periatrial and intercaval EAT volumes were significantly lower (12.8 ± 6.2 vs. 23.1 ± 13.9 ml/m , p < 0.02, and 1.1 ± 0.8 vs. 2.2 ± 1.6 ml/m , p< 0.02, respectively) and the patients were younger (66.5 ± 6.6 vs. 72.4 ± 8.3 years, p < 0.03) in the EC group than in the non-EC group. Conclusions: RAPW pacing revealed EC between the RA and right PV carina in nearly a quarter of the patients.

Abstract Background Right ventricular (RV) pacing causes changes of the electrical and mechanical activation pattern of the heart. QRS duration is reported to be a useful surrogate marker of electrical dyssynchrony, and wider QRS duration during RV pacing indicates poor prognosis. However, the mechanism of widening QRS duration during RV pacing remains to be elucidated. Methods A total of 211 patients who underwent catheter ablation for supraventricular tachyarrhythmias and have no bundle-branch-block on ECG were enrolled. During electrophysiological study, 3-dimensional mapping for QRS duration during RV pacing from RV outflow to RV apex was created, and the difference of QRS duration between RV outflow and RV apex was calculated. The relationship between QRS duration during RV pacing and patients' baseline characteristics including echocardiography data was analyzed. Results QRS duration at baseline, during RV pacing from RV outflow, and RV apex were 85.0±7.5msec, 156.2±16.1msec, and 163.7±17.1msec, respectively. The difference of QRS duration between RV outflow and RV apex among patients was only 12.5±10.4msec. The logistic multivariable regression analysis showed baseline QRS duration (odds ratio (OR) 1.24, 95% CI 1.15 to 1.34, p<0.01), interventricular septum thickness (OR 1.35, 95% CI 1.05 to 1.73, p=0.018), and E/e' (OR 1.23, 95% CI 1.12 to 1.36, p<0.01) were significant predictors for QRS duration over 160msec during RV apical pacing. Conclusions QRS duration during RV pacing depends largely not on the pacing site, but on the underlying structural heart disease. QRS duration mapping during RV pacing Funding Acknowledgement Type of funding source: None

Introduction: Although renoprotective effect of sodium glucose co-transporter-2 (SGLT2) inhibitors has been recognized in the patients with heart failure or type 2 diabetes mellitus (T2DM), this protection has not been fully examined in patients with acute myocardial infarction (AMI). We therefore examined renoprotection of the SGLT2 inhibitor empagliflozin in patients with AMI and T2DM. Methods: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of the SGLT inhibitor on cardiac sympathetic hyperactivity in patients with AMI and T2DM in Japan. One hundred and five patients were randomized (1:1) to receive once-daily 10-mg empagliflozin, or placebo 2 weeks after the onset of AMI. In this sub-analysis, we specifically focused on the time-course of renal function on baseline, weeks 4, 12 and 24. Results: Overall, 96 patients (64±11 y, 78 male) were included in the full analysis set (n = 46 and 50 in empagliflozin and placebo groups, respectively). In the placebo group, estimated glomerular filtration rate (eGFR) decreased from 66.1 at baseline to 62.8 mL/min/1.73m 2 on week 24, (P = 0.02). On the other hand, the empagliflozin group did not worsen it (from 64.6 to 64.4 mL/min/1.73m 2 , P = 0.84). The empagliflozin group exhibited the significant reduction in systolic blood pressure and uric acid level from baseline to week 24 (129.7 mmHg to 123.1 mmHg, P = 0.004, and 5.8 mg/dL to 4.9 mg/dL, P < 0.0001, respectively), whereas the reduction was not significant in the placebo group (123.1 mmHg to 126.2 mmHg, P = 0.19, and 5.7 mg/dL to 5.8 mg/dL, P = 0.82, respectively). The change in eGFR from baseline to 24 weeks was negatively correlated with the changes in uric acid in the placebo group (r=0.685, P<0.001), but not in the empagliflozin group. In stratified analysis among the patients with eGFR 60-90 mL/min/1.73m 2 , the empagliflozin group showed the significant increase in eGFR compared with the placebo group (+1.15 mL/min/1.73m 2 vs, - 6.43 mL/min/1.73m 2 , P=0.008), but not among the other population. Conclusions: Empagliflozin seemed to prevent the progression of renal dysfunction compared with placebo in the patients with AMI and T2DM. This tendency was remarkable when eGFR was 60-90 mL/min/1.73m 2 .

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 .

AIMS:The efficacy and safety of cardiac rehabilitation for patients with persistent atrial fibrillation who restored sinus rhythm after catheter ablation remains unclear. The aim of the present study was to evaluate the effects of cardiac rehabilitation on exercise capacity, inflammatory status, cardiac function, and safety in patients with persistent atrial fibrillation who had catheter ablation. METHODS:In this randomized controlled study, 61 patients treated with catheter ablation for persistent atrial fibrillation (male, 80%; mean age, 66 ± 9 years) were analyzed. Thirty patients underwent cardiac rehabilitation (rehabilitation group), whereas the remaining 31 patients received usual care (usual care group). The rehabilitation group underwent endurance and resistance training with moderate intensity, at least three times per week for six months. Six-minute walk distance, muscle strength, serum high-sensitivity C-reactive protein, plasma pentraxin 3, left ventricular ejection fraction and atrial fibrillation recurrence were assessed at baseline and at six-month follow-up. RESULTS:In the rehabilitation group, significant increases in the six-minute walk distance, handgrip strength, leg strength and left ventricular ejection fraction and significant decreases in high-sensitivity C-reactive protein and plasma pentraxin 3 concentrations were observed at six-month follow-up compared with baseline (all p < 0.05). No significant changes were observed in the usual care group. During the six-month follow-up period, the number of patients with atrial fibrillation recurrence was six (21.4%) in the rehabilitation group and eight (25.8%) in the usual care group (risk ratio, 0.83; 95% confidence interval, 0.33 to 2.10). CONCLUSIONS:Cardiac rehabilitation improved exercise capacity without increasing the risk for atrial fibrillation recurrence. It may also be effective in managing systemic inflammatory status and systolic left ventricular function in patients with persistent atrial fibrillation treated with catheter ablation.