Prognostic significance of the Holter-derived T-wave variability in patients with ventricular tachyarrhythmias complicating acute coronary syndrome-TWIST study.

BACKGROUND: We aimed to investigate the association between ventricular repolarization instability and sustained ventricular tachycardia and ventricular fibrillation (VT/VF) occurring within 48 h (acute-phase VT/VF) after the onset of acute coronary syndrome (ACS) and the prognostic role of repolarization instability and heart rate variability (HRV) after discharge from the hospital. METHODS: We studied 572 ACS patients with a left ventricular ejection fraction >35%. The ventricular repolarization instability was assessed by the beat-to-beat T-wave amplitude variability (TAV) using high-resolution 24-h Holter ECGs recorded at a median of 11 days from the date of admission. We calculated the HRV parameters including the deceleration capacity (DC) and non-Gaussian index calculated on a 25 s timescale (λ25s). The DC and λ25s were dichotomized based on previous studies' thresholds. RESULTS: Acute-phase VT/VF developed in 43 (7.5%) patients. In-hospital mortality was significantly higher among VT/VF patients (4.7% vs. 0.9%, p = .03). An adjusted logistic model showed that the maximum TAV (odds ratio 1.02, 95% confidence interval [CI] 1.00-1.29, p = .04) was associated with acute-phase VT/VF. During a median follow-up period of 2.1 years, 19 (3.3%) patients had cardiac deaths or resuscitated cardiac arrest. Acute-phase VT/VF (p = .12) and TAV (p = .72) were not significant predictors of survival. An age and sex-adjusted Cox model showed that the DC (p < .01), λ25s (p < .01), and emergency coronary intervention (p < .01) were independent predictors. CONCLUSION: T-wave amplitude variability was associated with acute-phase VT/VF, but the TAV was not predictive of survival post-discharge. The DC, λ25s, and emergency coronary intervention were independent predictors of survival.

Clinical utility of CorVue intrathoracic impedance alert with device-measured physical activity in predicting heart failure events.

Cardiac implantable electronic devices (CIEDs) offer heart failure (HF) diagnostic information, including intrathoracic impedance (ITI) or physical activity (PA). However, few studies have evaluated the utility of these parameters measured by CIEDs with CorVue algorithm. The purpose of this study was to investigate the relationship between ITI alerts triggered by the CorVue algorithm and HF development. We also examined the association between device-measured PA and ITI alerts associated with HF development. We retrospectively studied consecutive patients with CIEDs equipped with CorVue algorithm, which were implanted between June 1, 2011 and August 31, 2019. These patients were divided into two groups: patients with decreased ITI followed by the ITI alerts (ITI alert group) and those without the alerts (non-ITI alert group). There were 35 and 14 patients in the ITI and non-ITI alert groups, respectively. A total of 96 ITI alerts were observed. ITI alerts associated with HF development were observed in 21% (20/96); whereas, ITI alerts not associated with HF development were observed in 79% (76/96). Accurate device-measured PA was confirmed in 76 ITI alerts, which consisted of 30 alerts with lower PA and 46 alerts without lower PA. ITI alerts associated with HF development were observed in 30% (9/30) of the alerts with lower PA, whereas observed only in 6.5% (3/46) of the alerts without lower PA. In conclusion, the CorVue ITI alerts indicated a high false-positive rate. However, device-measured PA may be useful to determine whether ITI alerts are associated with HF development or not, which was attributed to the high negative predictive value.

Increased respiratory disturbance index measured using an advanced device algorithm is associated with heart failure development.

Previous studies suggested that sleep-disordered breathing was associated with cardiovascular diseases such as heart failure (HF). Recently, algorithms of cardiac implantable electronic devices (CIEDs) have been developed to detect advanced sleep apnea (SA); the Apnea Scan (AP Scan) being an example. The purpose of this study was to investigate the association between respiratory disturbance index (RDI) measured using the AP Scan algorithm and HF development. We retrospectively studied consecutive patients with CIEDs equipped with the AP Scan algorithm which were implanted between December 1, 2011 and March 31, 2019. These patients were divided into 2 groups according to the trends of RDI: patients with a continually high RDI > 30 (severe SA group) and those without a continually high RDI (non-severe SA group). There were 16 and 46 patients in the severe and non-severe SA groups, respectively. Increased left ventricular end-diastolic and end-systolic dimensions were observed in the severe SA group. Regarding cardiovascular events, HF was observed in 8 patients (50.0%) in the severe SA group and 1 patient (2.2%) in the non-severe SA group; thus, there was a significantly higher proportion of patients with HF in the severe SA group. In conclusion, continually high RDI was associated with HF development in patients with CIEDs equipped with the AP Scan algorithm. Therefore, an elevated RDI may be a risk factor for the development of HF in patients with CIEDs.

Laryngeal mask versus facemask in the respiratory management during catheter ablation.

BACKGROUND: The purpose of this study is to investigate if a laryngeal mask could improve respiratory condition during radiofrequency catheter ablation (RFCA). METHODS: Twenty-four consecutive patients who underwent RFCA for atrial fibrillation were divided into two groups (Facemask group; n = 10, Laryngeal mask group; n = 14). All patients were completely sedated under intravenous anesthesia and fitted with artificial respirators during the RFCA. The capnography waveforms and their differential coefficients were analyzed to evaluate the changes of end-tidal CO2 (ETCO2) values, respiratory intervals, expiratory durations, and inspiratory durations. RESULTS: During the RFCA, ETCO2 values of the laryngeal mask group were higher than those of the facemask group (36.0 vs. 29.2 mmHg, p = 0.005). The respiratory interval was significantly longer in the laryngeal mask group than those in the facemask group (4.28 s vs.5.25 s, p < 0.001). In both expiratory and inspiratory phases, the mean of the maximum and minimum values of CO2 was significantly higher when using a laryngeal mask than when using a facemask. The inspiratory-expiratory ratio of the laryngeal mask group was significantly larger than that of the facemask group (1.59 vs. 1.27, p < 0.001). The total procedure duration, fluoroscopic duration and the ablation energy were significantly lower in the laryngeal mask group than in the facemask group. The ETCO2 value is the most influential parameter on the fluoroscopic duration during the RFCA procedure (ß = - 0.477, p = 0.029). CONCLUSIONS: The use of a laryngeal mask could stabilize respiration during intravenous anesthesia, which could improve the efficiency of RFCA.

The presence of late potentials after percutaneous coronary intervention for the treatment of acute coronary syndrome as a predictor for future significant cardiac events resulting in re-hospitalization.

INTRODUCTION: We previously reported that LP positive patients after percutaneous coronary intervention (PCI) had higher rate of re-hospitalization in the small-scale study (135 patients). In this study, we evaluated correlation between LP and later cardiac events leading to re-hospitalization more extensively in greater population. METHODS AND RESULTS: A 24-h high-resolution (HR) ambulatory electrocardiogram (ECG) was performed in 421 patients that received PCI for the treatment of acute coronary syndrome (ACS) within 30 days. Various baseline characteristics and post-PCI ECG parameters including LP were examined for correlation with later re-hospitalization. LP was evaluated based on 3 different conditions, i.e., the worst, mean and best values, from 24-h signal-averaged QRS wave data. During the post-PCI follow-up period (611 ±â€¯489.0 days), 90 patients were re-hospitalized due to cardiac events. Multivariate analysis identified only positive LP based on the worst value as an independent predictor for re-hospitalization with OR 2.26. Most of re-hospitalization cases (>75%) were predominantly attributed to ischemic events. LP positive population had significantly higher incidences of ischemic events as well as overall re-hospitalization compared to LP negative population. The predictive power of LP was decreased when it was combined with other variables. The receiver operating characteristic analysis determined the LP cut-off values consistent with the LP positive criteria previously reported and standardized. CONCLUSION: The presence of LP in the 24-h HR ambulatory ECG post-PCI was an independent predictor for a risk of re-hospitalization due to ischemic cardiac events in ACS patients.

Left Atrial Appendage Thrombus Prior to Atrial Fibrillation Ablation in the Era of Direct Oral Anticoagulants.

BACKGROUND: In atrial fibrillation (AF) patients, the effect of direct oral anticoagulant (DOACs) therapy on the incidence of left atrial appendage thrombus (LAT) remains poorly investigated. This study examined the prevalence and risk factors of LAT in AF patients on DOACs undergoing catheter ablation, and sought an anticoagulation strategy for LAT. Methods and Results: In 407 AF patients on DOACs, transesophageal echocardiography (TEE) was performed 1 day before ablation. If patients had LAT, initial DOACs were switched to dabigatran (300 mg) or warfarin based on their renal function; TEE was repeated after treatment for ≥4 weeks. LAT was detected in 18 patients (4.4%). The prevalence of persistent AF and low-dose treatment/inappropriate dose reduction of DOACs, CHADS2/CHA2DS2-VASc scores, serum N-terminal pro-brain natriuretic peptide levels, and LA dimension/LA volume index significantly increased in patients with LAT vs. those without LAT. AF rhythm on TEE and spontaneous echo contrast also increased in patients with LAT; LA appendage flow velocity decreased. In the multivariate analysis, persistent AF and inappropriately reduced DOAC dose were risk factors for LAT. On repeat TEE, LAT had disappeared in 13 of 16 patients treated with dabigatran and in 2 of 2 patients treated with warfarin. CONCLUSIONS: DOACs still carry a finite risk of LAT in AF patients. Inappropriately reduced DOAC dose should be avoided to minimize the thromboembolic risk. Regular-dose dabigatran may have therapeutic efficacy against LAT.

Thromboembolisms in atrial fibrillation and heart failure patients with a preserved ejection fraction (HFpEF) compared to those with a reduced ejection fraction (HFrEF).

Heart failure (HF) is classified into three clinical subtypes: HF with a preserved ejection fraction (HFpEF: EF ≥ 50%), HF with a mid-range ejection fraction (HFmrEF: 40 ≤ EF < 49%), and HF with a reduced ejection fraction (HFrEF: EF < 40%). These types often coexist with atrial fibrillation (AF). We investigated the rate of strokes/systemic embolisms (SSEs) in AF patients with HFpEF (AF-HFpEF) compared to that in those with HFrEF (AF-HFrEF: HFmrEF and HFrEF), and examined the independent predictors. We prospectively enrolled 1350 patients admitted to our hospital for worsening HF. We identified 301 patients with either AF-HFpEF (n = 129, 43%) or AF-HFrEF (n = 172, 57%). Compared to the patients with AF-HFrEF, those with AF-HFpEF were older and more likely to be female. Oral anticoagulant use was 63 vs. 66%, respectively. During a mean follow-up period of 26 months, 21 (7%) and 66 (22%) patients had SSEs and all-cause death, respectively. The crude annual rates of SSEs (3.9 vs. 2.7%, P = 0.47) were similar between the groups. In a multivariate Cox regression analysis, an age ≥ 75 years (hazard ratio 2.14, 95% confidence interval 1.32-3.58, P < 0.01) and the plasma B-type natriuretic peptide (BNP) level ≥ 341 pg/ml (hazard ratio 1.60, 95% confidence interval 1.07-2.39, P < 0.05) were associated with SSEs. The EF was not an independent predictor of SSEs (hazard ratio 1.01, 95% confidence interval 0.98-1.04, P = 0.51). There were no significant differences in the rates of SSEs between AF-HFpEF and AF-HFrEF. Patients with HF and concomitant AF should be treated with anticoagulants irrespective of EF.

Prognostic Importance of Novel Oxygen Desaturation Metrics in Patients With Heart Failure and Central Sleep Apnea.

BACKGROUND: Sleep-disordered breathing, particularly central sleep apnea (CSA), is highly prevalent in heart failure (HF) and an independent prognostic marker. We assessed the hypothesis that an increased hypoxemic burden during sleep may have greater prognostic value than the frequency of apneic and hypopneic episodes. METHODS AND RESULTS: We prospectively conducted overnight cardiorespiratory polygraphy on consecutive HF patients referred to our hospital from 2008 to 2011. We studied CSA defined by an apnea-hypopnea index (AHI) of ≥5 events/h with >75% of all events being central in origin. We determined the AHI, proportion of the sleep time with SpO2 <90% (T90%), and proportion of the recording time that 4% desaturation events occurred (4%POD). We studied 112 HF patients with either systolic or diastolic dysfunction. During a follow-up period of 37 ± 25 months, 32 patients (29%) died. Nonsurvivors had a higher 4%POD compared with survivors (11 ± 6.4% vs 19 ± 13%; P = .001), but did not differ significantly from survivors regarding AHI and T90%. An adjusted logistic regression analysis revealed that the 4%POD was the best independent predictor of mortality. CONCLUSIONS: The 4%POD, a novel metric for the nocturnal hypoxemic burden, is an independent prognostic marker in HF patients affected by CSA.

Beat-to-beat T-wave amplitude variability in the risk stratification of right ventricular outflow tract-premature ventricular complex patients.

AIMS: Premature ventricular complexes (PVCs) originating from the right ventricular outflow tract (RVOT) may occasionally trigger monomorphic ventricular tachycardia (MVT), polymorphic ventricular tachycardia (PVT), or ventricular fibrillation (VF). We examined whether an analysis of the ventricular repolarization instability could differentiate PVT/VF triggered by RVOT-PVCs from benign RVOT-PVCs or MVT. METHODS: We evaluated the ventricular repolarization instability as assessed by the beat-to-beat T-wave amplitude variability (TAV) using Holter recordings in patients with RVOT-PVCs but with no structural heart disease. We determined the prematurity index, defined as the ratio of the coupling interval of the first ventricular tachycardia (VT) beat or isolated PVC to the preceding R-R interval just before the VT or isolated PVC in the Holter recordings. The study patients were classified into RVOT-PVCs/MVT (n = 33) and PVT/VF (n = 10). RESULTS: The two groups did not differ with respect to the age, sex, and left ventricular ejection fraction. There was no significant difference in the prematurity index between the two groups (RVOT-PVCs/MVT 0.66 ± 0.16 vs. PVT/VF 0.61 ± 0.13, P = 0.60). The patients with PVT/VF had a significantly larger maximum TAV than those with RVOT-PVCs/MVT (31 ± 13 vs. 68 ± 40 µV, P < 0.001). Patients with a higher than median value of the TAV (33 µV) were at increased risk of PVT/VF vs. those with a lower than median value, after adjusting for the age and sex [9.25 (95% confidence interval: 1.27-19.2); P = 0.03]. CONCLUSIONS: The TAV analysis is a useful measure to identify the subset of usually benign RVOT-PVC/MVT patients prone to PVT/VF.

Clinical utility of the "balloon lever technique" in the right inferior pulmonary vein cryoballoon ablation.

Background: The acute success rate of pulmonary vein isolation (PVI) with cryoballoon (CB) is reported to be lower in the right inferior pulmonary vein (RIPV). This study aimed to investigate the utility of the "balloon lever technique (BLT)" for RIPV CB ablation. Methods: We retrospectively studied consecutive patients who underwent CB-PVI for atrial fibrillation between February 21, 2020 and June 3, 2022. RIPV cryoablation was performed according to a specific protocol. The patients underwent RIPV cryoablation using the conventional method. If the method was found ineffective, BLT cryoablation was performed. The acute success rate of RIPV CB ablation was examined. We also investigated the RIPV isolation rate and procedural parameters during conventional and BLT cryoablation. Results: Ninety-three patients were included in the analysis. RIPV isolation was achieved in 89.2% (83/93) of the patients using conventional method and subsequent BLT cryoablation. Meanwhile, 68 patients underwent BLT cryoablation because the conventional method was ineffective. RIPV was isolated with BLT in 85.3% (58/68) of patients. Additionally, BLT was found to be superior to conventional cryoablation in terms of nadir balloon temperature, freezing time, and thawing time to a specific temperature in patients who underwent both conventional and BLT cryoablations. Conclusions: BLT is useful in RIPV cryoablation when the conventional method is ineffective. BLT cryoablation may be helpful, mainly because of the BLT-mediated contact of the balloon with the bottom of the RIPV, which leads to optimal RIPV occlusion.

Association of device-measured physical activity with peak oxygen consumption measured by cardiopulmonary exercise testing in patients with cardiac implantable electronic devices.

PURPOSE: Cardiac implantable electronic devices (CIEDs) offer diagnostic information such as device-measured physical activity (PA). Peak oxygen consumption (VO2) measured by cardiopulmonary exercise testing (CPET) is the most objective variable showing exercise capacity. The purpose of this study was to investigate the relationship between these 2 variables. METHODS: We retrospectively studied consecutive patients with CIEDs undergoing CPET between April 1, 2018, and January 31, 2021. These patients were divided into 2 groups: patients with peak VO2 ≤ 14 ml/kg/min (low peak VO2 group) and those showing peak VO2 > 14 ml/kg/min (high peak VO2 group). The peak device-measured PA was compared between the 2 groups. The relationship between the peak device-measured PA and peak VO2 was also investigated. RESULTS: There were 50 and 51 patients in the low and high peak VO2 groups, respectively. The peak device-measured PA, which was expressed in units of hours/day, was significantly lower in the low peak VO2 group than in the high peak VO2 group (3.06, interquartile range [2.43-4.00] vs. 5.50, interquartile range [4.04-6.70] p < 0.01). The peak device-measured PA and peak VO2 showed a significant positive correlation (Spearman's ρ = 0.53; p < 0.01). Furthermore, receiver operating characteristic curve analysis showed that a peak device-measured PA > 3.87 h/day could predict high peak VO2 (80.4%, sensitivity; 72.0%, specificity). In multivariate linear regression analysis, peak device-measured PA was an independent predictor of peak VO2 (regression coefficient, 0.61; 95% confidence interval, 0.33-0.89; p < 0.01). CONCLUSIONS: Peak device-measured PA was significantly associated with peak VO2.

Ectopic discharge originating from the ostium of the inferior vena cava that is likely to cause atrial fibrillation.

It has been established that the initiation of paroxysmal atrial fibrillation (AF) is frequently associated with ectopic beats inside the thoracic veins, including the pulmonary veins, superior vena cava, coronary sinus, and/or vein of Marshall. However, similar arrhythmogenic ectopic discharge or premature atrial contractions (PACs) originating from the inferior vena cava (IVC) have been rarely described. We present the case of a 51-year-old man with paroxysmal AF undergoing electrophysiological study. Twelve-lead electrocardiography demonstrated PACs with negative P waves in the inferior leads. Ectopic beats originating from the ostium of the IVC, which were likely to initiate AF, were observed. Furthermore, the origin of the PAC was visualized using an electroanatomical local activation timing (LAT) map and located close to the fibrotic tissue of the vasculature. Radiofrequency catheter ablation was performed at the earliest activation site, and ectopic beats were not observed after the procedure. This is the first report to demonstrate a LAT contact map of ectopic discharge arising from the IVC. If PACs with negative P waves in the inferior leads are found in a patient with AF, the IVC should be investigated for possible focal ectopic discharges. Learning objective: Non-pulmonary vein foci play a significant role in the pathogenesis of atrial fibrillation (AF). However, inferior vena cava (IVC) triggers that initiate AF have rarely been described. Premature atrial contractions with negative P waves in the inferior leads may be associated with ectopic discharges originating from the IVC, which contribute to the initiation of AF.

A successful treatment of ganglionated plexi ablation for vagally mediated nocturnal atrioventricular block.

Patients suffering from sleep-related bradyarrhythmias are often underdiagnosed, due to the presence of asymptomatic cases. Although the consequence of increased nocturnal parasympathetic nerve activities and decreased sympathetic nerve activity during sleep are associated with nocturnal bradyarrhythmias, the detailed mechanisms are still unknown. It is well known that ganglionated plexi (GP) ablation is an effective therapeutic approach to modify autonomic nerve functions. Here, we report a case of successful treatment for the vagally mediated long ventricular pauses during sleep using autonomic modulation through GP ablation. Learning objective: Sleep-related bradyarrhythmias unrelated to sleep apnea or hypopnea are rare sleep disorders. Treatment of this disorder has not been established. High-frequency stimulation guided ganglionated plexi ablation could be an effective therapeutic approach to achieve long-term vagal attenuation to prevent vagally induced nocturnal bradyarrhythmias.

Technology Applications of Capnography Waveform Analytics for Evaluation of Heart Failure Severity.

This study aimed to elucidate the influential parameter, acquired from the analyses of nasal capnography waveforms, for the elevated plasma brain natriuretic peptide (BNP) levels in patients (n = 34) with heart failure (HF). The capnography waveforms were analyzed to evaluate changes in end-tidal CO2 (ETCO2) values and expiratory and inspiratory durations. The relationship between these parameters, estimated from capnography analyses and plasma BNP, was then evaluated. Mean ETCO2 values and BNP levels showed a strong negative correlation (R2 = 0.6355, p < 0.0001) in HF patients with chronic kidney disease (CKD) (R2 = 0.6355, p < 0.0001). The ETCO2 value was the most influential parameter that indicated elevated BNP levels in HF patients with CKD (ß = - 0.577; p = 0.031). The mean ETCO2 level could be a potentially influential parameter reflecting elevated BNP levels in HF patients, especially in HF patients with CKD. Respiratory parameters, acquired from detailed nasal capnography analyses, might be reasonable for evaluating the severity of HF. Graphical abstract.

An application of pacemaker respiratory monitoring system for the prediction of heart failure.

Sleep-disordered breathing (SDB) is one of the most common complications among heart failure (HF) patients. Changes of respiratory patterns during the various stages in patients with HF have not been fully investigated. In this case, the algorism using thoracic impedance sensor and minute ventilation (sleep apnea monitoring [SAM] algorithm) with implanted pacemaker (REPLY 200 SR or DR, Sorin CRM SAS, Clamart, France) was used to monitor respiration. Impedance data from the implanted pacemaker can be converted into respiratory data, which can be used to calculate the respiratory disturbance index (RDI) per unit of time. Using this algorithm, we observed a sudden appearance of abnormal breathing at the onset of HF, followed by gradual improvement of respiratory patterns during the recovery stage. The results from respiratory monitoring using the SAM algorithm were strongly correlated with those from the positive airway pressure device. This case report could imply that proper utilization of this sensor could facilitate the early detection and therapeutic control of HF.

Impact of serum albumin levels on supratherapeutic PT-INR control and bleeding risk in atrial fibrillation patients on warfarin: A prospective cohort study.

BACKGROUND: Since warfarin is primarily bound to serum albumin, hypoalbuminemia is likely to increase the free fraction of warfarin and to increase the risk of bleeding. We prospectively evaluated the impact of serum albumin levels (ALB) on international normalized ratio of prothrombin time (PT-INR) control and hemorrhagic events in atrial fibrillation (AF) patients treated with warfarin. METHODS: Seven hundred fifty-five non-valvular AF patients on warfarin were enrolled. PT-INR control and major bleeding events (MB, International Society on Thrombosis and Haemostasis) were prospectively followed and were related to ALB at enrollment. RESULTS: Twenty-seven patients developed MB during 1-year follow-up. In univariate/multivariate analyses, ALB (OR = 0.49, 95% CI 0.26-0.99, p = 0.04) and hemoglobin levels (OR = 0.78, 95% CI 0.65-0.92, p = < 0.01) were predictive for the annual risk of MB. In Spearman's rank correlation analysis, the baseline ALB was inversely correlated with the percentage of the time in PT-INR > 3.0 (ρ = -0.15, p < 0.0001), but neither 2.0 ≤ PT-INR ≤ 3.0 (ρ = 0.056, p = 0.13) nor PT-INR < 2.0 (ρ = -0.008, p = 0.82) during 1-year follow-up, suggesting that patients with low ALB had a directional tendency to be supratherapeutic control of PT-INR. The ROC curve showed that a cutoff of ALB was 3.6 g/dl to identify MB (AUC = 0.65). In Kaplan-Meier analysis, patients with ALB <3.6 g/dl (23/80, 29%) had more MB than those with ALB ≥3.6 g/dl (87/675, 13%, log-rank = 16.80, p < 0.0001) during long-term follow-up (3.8 ±â€¯2.0 years). CONCLUSIONS: Hypoalbuminemia increases the likelihood of supratherapeutic PT-INR control and the risk of MB. ALB can be a practical surrogate marker to prevent excessive warfarin control and warfarin-related MB.

Continuous Positive Airway Pressure Therapy Improves Heterogeneity of R-R intervals in a Patient with Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea (OSA) is associated with the occurrence of various kinds of bradyarrhythmia and tachyarrhythmia. The activation of the autonomic nerve system is an important causative factor of the pathogenesis of the arrhythmia in OSA patients. Previous studies have shown that the R-R interval is an effective parameter for evaluating autonomic nerve activities. However, whether or not OSA can induce variations in the R-R interval and whether or not continuous positive airway pressure (CPAP) therapy can improve these variations in OSA patients are unclear. The present study explored whether or not CPAP therapy could improve the regularity of the R-R interval.

Physically triggered Takotsubo cardiomyopathy has a higher in-hospital mortality rate.

BACKGROUND: Takotsubo cardiomyopathy (TC) is a myopathy triggered by severe stressful events. However, little is known about the determinants of in-hospital outcomes. We prospectively determined the effect of different triggers on the prognosis of TC. METHODS AND RESULTS: We enrolled patients who were admitted for suspected acute coronary syndrome (ACS) from January 2008 to December 2015. TC was diagnosed according to the Mayo Clinic diagnosis criteria. The outcome was in-hospital death. Among 1861 consecutive patients with suspected ACS, 82 (4.4%) patients were diagnosed with TC. There were 43 patients (52%) with physical triggers (Physical), 26 (31%) with emotional triggers, and 13 (17%) with no identifiable triggers. The latter two groups were combined and categorized as the Non-physical trigger group. Compared with non-physical triggered TC, patients with physical triggered TC were more likely to have a malignancy (p=0.008), lower blood pressure (p=0.001), lower hemoglobin (p<0.001), higher serum creatinine (p<0.001) and higher norepinephrine levels (p=0.007). During a mean hospital stay of 16±12days, 9 (20.9%) of the Physical and 1 (2.6%) of the Non-physical patients died in-hospital (log-rank p=0.007). After adjusting for the age, gender, trigger, malignancy, and hemoglobin level, being male (hazard ratio 11.9, 95% confidence interval, 2.43-58.5, p=0.002) and having a physical trigger (14.7, 1.19-166, p=0.03) were associated with in-hospital mortality. CONCLUSION: There was a significant difference in in-hospital mortality depending on the trigger type in TC. Being male and having a physical trigger were independent risk factors of in-hospital mortality from TC.

Multiscale Entropy of the Heart Rate Variability for the Prediction of an Ischemic Stroke in Patients with Permanent Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a significant risk factor for ischemic strokes, and making a robust risk stratification scheme would be important. Few studies have examined whether nonlinear dynamics of the heart rate could predict ischemic strokes in AF. We examined whether a novel complexity measurement of the heart rate variability called multiscale entropy (MSE) was a useful risk stratification measure of ischemic strokes in patients with permanent AF. METHODS AND RESULTS: We examined 173 consecutive patients (age 69 ± 11 years) with permanent AF who underwent 24-hour Holter electrocardiography from April 2005 to December 2006. We assessed several frequency ranges of the MSE and CHA2DS2-VASc score (1 point for congestive heart failure, hypertension, diabetes, vascular disease, an age 65 to 74 years, and a female sex and 2 points for an age ≥ 75 years and a stroke or transient ischemic attack). We found 22 (13%) incident ischemic strokes during a mean follow up of 3.8-years. The average value of the MSE in the very-low frequency subrange (90-300 s, MeanEnVLF2) was significantly higher in patients who developed ischemic strokes than in those who did not (0.68 ± 0.15 vs. 0.60±0.14, P<0.01). There was no significant difference in the C-statistic between the CHA2DS2-VASc score and MeanEnVLF2 (0.56; 95% confidence interval, 0.43-0.69 vs. 0.66; 95% confidence interval, 0.53-0.79). After an adjustment for the age, CHA2DS2-VASc score, and antithrombotic agent, a Cox hazard regression model revealed that the MeanEnVLF2 was an independent predictor of an ischemic stroke (hazard ratio per 1-SD increment, 1.80; 95% confidence interval, 1.17-2.07, P<0.01). CONCLUSION: The MeanEnVLF2 in 24-hour Holter electrocardiography is a useful risk stratification measure of ischemic strokes during the long-term follow-up in patients with permanent AF.