Addressing out-of-hospital cardiac arrest with current technology advances: Breaking the deadlock with a mobile network.

Out-of-hospital cardiac arrest (OHCA) is a global public health problem, with survival rates remaining low at around 10% or less despite widespread cardiopulmonary resuscitation (CPR) training and availability of automated external defibrillators (AEDs). This is partly due to the challenges of knowing when and where a sudden OHCA occurs and where the nearest AED is located. In response, countries around the world have begun to use network technology-based smartphone applications. These applications are activated by emergency medical service dispatchers and alert preregistered volunteer first responders (VFRs) to nearby OHCAs using Global Positioning System localization. Accumulating evidence, although mostly from observational studies, shows their effectiveness in increasing the rate of bystander CPR, defibrillation, and patient survival. Current guidelines recommend the use of these VFR alerting systems, and the results of ongoing randomized trials are awaited for further dissemination. This article also proposed the concept of a life-saving mobile network (LMN), which uses opportunistic network and wireless sensor network technologies to create a dynamic mesh network of potential victims, rescuers, and defibrillators. The LMN works by detecting a fatal arrhythmia with a wearable sensor device, localizing the victim and the nearest AED with nearby smartphones, and notifying VFRs through peer-to-peer communication. While there are challenges and limitations to implementing the LMN in society, this innovative network technology would reduce the tragedy of sudden cardiac death from OHCA.

Tensor cardiography: A novel ECG analysis of deviations in collective myocardial action potential transitions based on point processes and cumulative distribution functions.

To improve clinical diagnoses, assessments of potential cardiac disease risk, and predictions of lethal arrhythmias, the analysis of electrocardiograms (ECGs) requires a more accurate method of weighting waveforms to efficiently detect abnormalities that appear as minute strains in the waveforms. In addition, the inverse problem of estimating the myocardial action potential from the ECG has been a longstanding challenge. To analyze the variance of the ECG waveforms and to estimate collective myocardial action potentials (APs) from the ECG, we designed a model equation incorporating the probability densities of Gaussian functions of time-series point processes in the cardiac cycle and dipoles of the collective APs in the myocardium. The equation, which involves taking the difference between the cumulative distribution functions (CDFs) that represent positive endocardial and negative epicardial potentials, fits both R and T waves. The mean, standard deviation, weights, and level of each cumulative distribution function (CDF) are metrics for the variance of the transition state of the collective myocardial AP. Clinical ECGs of myocardial ischemia during coronary intervention show abnormalities in the aforementioned specific elements of the tensor associated with repolarization transition variance earlier than in conventional indicators of ischemia. The tensor can be used to evaluate the beat-to-beat dynamic repolarization changes between the ventricular epi and endocardium in terms of the Mahalanobis distance (MD). This tensor-based cardiography that uses the differences between CDFs to show changes in collective myocardial APs has the potential to be a new analysis tool for ECGs.

Impact of polypharmacy on 3-year mortality in patients with heart failure: a retrospective study.

BACKGROUND: Guideline-directed medical therapy (GDMT) is important in heart failure management; however, polypharmacy itself may impact heart failure. Although measures against polypharmacy are needed, current discussion on unilateral drug tapering (including the drugs that should be tapered) is insufficient. In this study, we investigated the relationship between the number of prescribed GDMT drugs and prognosis in patients with heart failure. METHODS: In this single-centre retrospective study, 3,146 eligible patients with heart failure were included and divided into four groups based on the median number of prescribed GDMT drugs and the median number of drugs not included in the GDMT (ni-GDMT) at the time of hospital discharge. The definition of GDMT was based on various Japanese guidelines. The primary outcome was all-cause mortality within 3 years of hospital discharge. RESULTS: A total of 252 deaths were observed during the 3-year follow-up period. Kaplan-Meier analysis revealed that groups with GDMT drug count ≥ 5 and ni-GDMT drug count < 4 had the lowest mortality, and those with GDMT drug count < 5 and ni-GDMT drug count ≥ 4 had the highest mortality (log-rank, P < 0.001). Cox regression analysis revealed a significant association between ni-GDMT drug count and all-cause mortality, even after adjustment for number of GDMT medications, age, male, left ventricular ejection function < 40%, hemoglobin, albumin levels, and estimated glomerular filtration rate [HR = 1.06 (95% CI: 1.01-1.11), P = 0.020]. Conversely, the GDMT drug count was not associated with increased mortality rates. CONCLUSIONS: The ni-GDMT drug count was significantly associated with 3-year mortality in patients with heart failure. Conversely, the GDMT drug count did not worsen the prognosis. Polypharmacy measures should consider ni-GDMT drug quantity to improve the prognosis and outcomes in patients with heart failure.

Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study.

Background: Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods: We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results: Not applicable. Conclusion: This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

Prognostic impact of plasma volume status during hospital admission in patients with acute decompensated heart failure.

AIMS: Plasma volume status (PVS), a measure of plasma volume, has been evaluated as a prognostic marker for chronic heart failure. Although the prognostic value of PVS has been reported, its significance in patients with acute decompensated heart failure (ADHF) admitted to the cardiovascular intensive care unit (CICU) remains unclear. In this study, we examined the relationship between PVS and long-term mortality in patients with ADHF admitted to the CICU. METHODS: Between January 2018 and December 2020, 363 consecutive patients with ADHF were admitted to the Nippon Medical School Hospital CICU. Of the 363 patients, 206 (mean age, 74.9 ± 12.9 years; men, 64.6%) were enrolled in this study. Patients who received red blood cell transfusions, underwent dialysis, were discharged from the CICU or died in the hospital were excluded from the study. We measured the PVS of the patients at admission, transfer to the general ward (GW) and discharge using the Kaplan-Hakim formula. The patients were assigned to four groups according to the quartiles of their PVS measured at each of the three abovementioned timepoints. We examined the association between PVS and all-cause mortality during the observation period (1134 days). The primary endpoint of this study was all-cause mortality. RESULTS: The Kaplan-Meier analysis showed that the high PVS group had a significantly higher mortality rate at admission, transfer to the GW and discharge than the other groups (log-rank test: P = 0.016, P = 0.005 and P < 0.001, respectively). Univariate Cox regression analysis showed that age, body mass index, history of heart failure, use of beta-blockers, albumin level, blood urea nitrogen level, N-terminal pro-brain natriuretic peptide level and left ventricular ejection fraction were significantly different among the PVS groups and thus were not significant prognostic factors for ADHF. Furthermore, the multivariate analysis revealed that PVS at discharge [hazard ratio (HR) = 1.06 (1.00-1.12), P = 0.048] was an independent poor prognostic factor for ADHF. CONCLUSIONS: This study highlights the effect of PVS measured at different timepoints on the prognoses of ADHF patients. Regular assessment of PVS, particularly at discharge, is crucial for optimising patient management and achieving favourable outcomes in cases of ADHF.

Fractional excretion of urea nitrogen can identify true worsening renal function in patients with heart failure.

AIMS: Fractional excretion of urea nitrogen (FEUN), used to differentiate the cause of acute kidney injury, has emerged as a useful fluid index in patients with heart failure (HF). We hypothesized that FEUN could be useful in identifying worsening renal function (WRF) associated with poor outcomes in patients with acute HF (AHF). METHODS AND RESULTS: Overall, 1103 patients with AHF (median age, 78 years; male proportion, 60%) were categorized into six groups according to the presence of WRF and FEUN values (low, ≤32.1%; medium, >32.1% and ≤38.0%; and high, >38.0%) at discharge. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). The cut-off values for low, medium, and high FEUN were based on a previous study. The primary outcome of this study was HF readmission after hospital discharge. During the 1 year follow-up, 170 HF readmissions occurred. Kaplan-Meier analysis revealed significantly higher HF readmission rates in patients with WRF than in those without WRF (log-rank test, P < 0.001). Additionally, among patients with WRF, HF readmission rates were lowest in those with medium FEUN values, followed by those with low FEUN values and those with high FEUN values. On multivariable analysis, the presence of WRF with low or high FEUN values was independently associated with increased HF readmission, as compared with the absence of WRF with medium FEUN values. Notably, no association was noted between WRF with medium FEUN values and HF readmission. CONCLUSIONS: The prognostic impact of WRF was significantly mediated by the FEUN values and was associated with worse outcomes only when the FEUN values were either low or high. Our study suggests that FEUN can identify prognostically relevant WRF in patients with AHF.

Impact of Red Blood Cell Transfusion on Subsequent Cardiovascular Events in Patients with Acute Heart Failure and Anemia.

Red blood cell (RBC) transfusion therapy is often performed in patients with acute heart failure (AHF) and anemia; however, its impact on subsequent cardiovascular events is unclear. We examined whether RBC transfusion influences major adverse cardiovascular events (MACE) after discharge in patients with AHF and anemia.We classified patients with AHF and anemia (nadir hemoglobin level < 10 g/dL) according to whether they received RBC transfusion during hospitalization. The endpoint was MACE (composite of all-cause death, non-fatal acute coronary syndrome/stroke, or heart failure readmission) 180 days after discharge. For survival analysis, we used propensity score matching analysis with the log-rank test. As sensitivity analysis, we performed inverse probability weighting analysis and multivariable Cox regression analysis.Among 448 patients with AHF and anemia (median age, 81 years; male, 55%), 155 received RBC transfusion and 293 did not. The transfused patients had worse clinical features than the non-transfused patients, with lower levels of nadir hemoglobin and serum albumin and a lower estimated glomerular filtration rate. In the propensity-matched cohort of 87 pairs, there was no significant difference in the MACE-free survival rate between the 2 groups (transfused, 73.8% vs. non-transfused, 65.3%; P = 0.317). This result was consistent in the inverse probability weighting analysis (transfused, 76.0% vs. non-transfused, 68.7%; P = 0.512), and RBC transfusion was not significantly associated with post-discharge MACE in the multivariable Cox regression analysis (adjusted hazard ratio: 1.468, 95% confidence interval: 0.976-2.207; P = 0.065).In conclusion, this study suggests that RBC transfusions for anemia may not improve clinical outcomes in patients with AHF.

Electrophysiological and Histopathological Characteristics of Ventricular Tachycardia Associated With Primary Cardiac Tumors.

BACKGROUND: Ventricular tachycardia (VT) associated with primary cardiac tumors (PCTs) originating from the ventricles is rare, but lethal, in young patients. OBJECTIVES: This study aimed to clarify the mechanisms underlying primary cardiac tumor-related ventricular tachycardia (PCT-VT) and establish a therapeutic strategy for this form of VT. METHODS: Among 67 patients who underwent surgery for VT at our institute between 1981 and 2020, 4 patients aged 1 to 34 years, including 3 males, showed PCT-VT (fibroma, 2; lipoma, 1; and hamartoma, 1), which was investigated using a combination of intraoperative electroanatomical mapping and histopathological studies. RESULTS: All 4 patients developed electrical storms of sustained VTs refractory to multiple drugs and repetitive endocardial ablations. The VT mechanism was re-entry, and intraoperative electroanatomical mapping showed a centrifugal activation pattern originating from the border between the tumor and healthy myocardium, where fractionated potentials were detected during sinus rhythm. Histopathological studies of serial sections of specimens acquired from these areas revealed tumor infiltration into the surrounding myocardium with cell disorganization, exhibiting myocardial disarray. Several myocardia entrapped in the tumor edges contributed to the development and sustainment of re-entrant VT activation. In the 2 patients in whom complete resection was unfeasible, encircling cryoablation to entirely isolate the unresectable tumor was effective in suppressing VT occurrence. CONCLUSIONS: The mechanism underlying PCT-VT involves re-entry localized at the tumor edges. Myocardial disarray associated with tumor infiltration is a substrate for this form of VT. Cryoablation along the border between the tumor and myocardium is a promising therapeutic option for unresectable PCT-VT.

The Japanese Catheter Ablation Registry (J-AB): Annual report in 2021.

The Japanese Catheter Ablation (J-AB) registry, started in August 2017, is a voluntary, nationwide, multicenter, prospective, observational registry, performed by the Japanese Heart Rhythm Society (JHRS) in collaboration with the National Cerebral and Cardiovascular Center using a Research Electronic Data Capture system. The purpose of this registry is to collect the details of target arrhythmias, the ablation procedures, including the type of target arrhythmias, outcomes, and acute complications in the real-world settings. During the year of 2021, we have collected a total of 89 609 procedures (mean age of 66.1 years and 65.9% male) from 506 participant hospitals. Detailed data are shown in Figures and Tables.

Enlarged right atrium predicts pacemaker implantation after atrial fibrillation ablation in patients with tachycardia-bradycardia syndrome.

Introduction: Although catheter ablation (CA) of tachycardia-bradycardia syndrome (TBS) in patients with atrial fibrillation (AF) is considered to be an effective treatment strategy, pacemaker implantations (PMIs) are often required even after a successful CA. This study aimed to elucidate the clinical predictors of a PMI after CA. Methods: From 2011 to 2020, 103 consecutive patients diagnosed with TBS were retrospectively enrolled in the study. Among the 103 patients, 54 underwent a PMI and 49 CA of AF. During 47.4 ± 35.4 months after 1.4 ± 0.6 CA sessions, 37 (75.5%) of 49 patients were free from atrial arrhythmia recurrences. PMIs were performed in 11 patients (PMI group) and the remaining 38 did not receive a PMI (non-PMI group). Results: When comparing the PMI and non-PMI groups, there were no differences in the basic mean heart rate (P = 0.36), maximum pauses detected by 24-hour Holter-monitoring (P = 0.61), and other clinical parameters between the two groups while the right atrial area index was larger (42.1 ± 24.0 vs. 21.8 ± 8.4 cm2/m2 P = 0.002) in the PMI group than non-PMI group. The ROC curve analysis showed that the optimal cutoff point of the ratio of the right atrial area index to the left atrial area index for predicting a PMI following CA was 0.812 (Sensitivity 72.7%, specificity 71.1%, positive predictive value 42.1%, negative predictive value 90.0%, diagnostic accuracy 71.4%, AUC = 0.81). Conclusion: Right atrial enlargement prior to CA was considered to be one of the risk factors for a PMI after CA of AF.

Preferred left ventricular lead position for upgrade from right ventricular pacing to cardiac resynchronization therapy.

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.

Utility of fractional excretion of urea nitrogen in heart failure patients with chronic kidney disease.

AIMS: Maintenance of euvolaemia with diuretics is critical in heart failure (HF) patients with chronic kidney disease (CKD); however, it is challenging because no reliable marker of volume status exists. Fractional excretion of urea nitrogen (FEUN) is a useful index of volume status in patients with renal failure. We aimed to examine whether FEUN is a surrogate marker of volume status for risk stratification in HF patients with CKD. METHODS AND RESULTS: We examined 516 HF patients with CKD (defined as discharge estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) whose FEUN was measured at discharge (median age, 80 years; 58% male). The patients were divided into four groups according to quartile FEUN value at discharge: low-FEUN, FEUN ≤ 32.1; medium-FEUN, 32.1 < FEUN ≤ 38.0; high-FEUN, 38.0 < FEUN ≤ 43.7; and extremely-high-FEUN, FEUN > 43.7. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). During the 3 year follow-up, 131 HF readmissions occurred. Kaplan-Meier analysis showed that the HF readmission rate was significantly lower in the medium-FEUN group than in the other three groups (log-rank test, P = 0.029). Multivariate Cox regression analysis identified the low-FEUN, high-FEUN, and extremely-high-FEUN values as independent factors associated with post-discharge HF readmission. In the analysis of 130 patients who underwent right heart catheterization during hospitalization, a significant correlation between FEUN value and right atrial pressure was observed (R = 0.243, P = 0.005). Multivariate linear regression analysis revealed that FEUN value at discharge decreased in a dose-dependent manner with loop diuretics. CONCLUSIONS: In HF patients with CKD, FEUN is a potential marker of volume status for risk stratification of post-discharge HF readmission. Low FEUN value (FEUN ≤ 32.1) may represent intravascular dehydration, whereas high FEUN value (FEUN > 38.0) may represent residual congestion; both of them were independent risk factors for HF readmission. FEUN may be useful to determine euvolaemia and guide fluid management in HF patients with CKD.

Registry for Evaluating Healthy Life Expectancy and Long-Term Outcomes after Catheter Ablation of Atrial Fibrillation in the Very Elderly (REHEALTH AF) study: rationale and design of a prospective, multicentre, observational, comparative study.

INTRODUCTION: Data are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients' postablation quality of life (QoL) and long-term clinical outcomes. METHODS AND ANALYSIS: We are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician's advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient's Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results. ETHICS AND DISSEMINATION: The study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000047023.