Pediatric hypertrophic cardiomyopathy caused by a novel TNNI3 variant.

TNNI3 is a gene that causes hypertrophic cardiomyopathy (HCM). A 14-year-old girl who was diagnosed with nonobstructive HCM presented with cardiopulmonary arrest due to ventricular fibrillation. Genetic testing revealed a novel de novo heterozygous missense variant in TNNI3, NM_000363.5:c.583A>T (p.Ile195Phe), which was determined to be the pathogenic variant. The patient exhibited progressive myocardial fibrosis, left ventricular remodeling, and life-threatening arrhythmias. Genetic testing within families is useful for risk stratification in pediatric HCM patients.

Feasibility of a novel atrial mechanical sensing method for leadless atrioventricular synchronous pacing.

INTRODUCTION: Few studies have demonstrated a high degree of atrioventricular (AV) synchrony with a new leadless pacemaker called Micra AV. Our group previously reported a new and unique sensing method. We believe that this novel sensing method, "Simplified A3 method," might facilitate better AV synchrony than a conventional sensing method in almost all cases with Micra AV implantation. METHODS: We conducted a non-randomized retrospective study comparing the two pacing methods at two centers. From December 1, 2021 to October 31, 2022, Micra AV was implanted for 32 patients at the two centers. Twenty of the 32 patients with sinus rhythm and complete AV block were included in this study. In Group 1, the conventional setting was programmed as follows: auto A3 threshold, auto A3 window-end (WE), and auto A4 threshold turned on during hospitalization. In Group 2, the "Simplified A3 method" was programmed as follows: auto A3 threshold and auto A3WE turned off. Instead, an intentionally prolonged A3WE (850-1000 ms) and low A3 threshold (A3 signal amplitude + 0.5-1.0 m/s2) were programmed. RESULTS: Twenty patients were analyzed. In Group 2, AV synchrony (%AMVp) was significantly higher at the first outpatient clinic (63.0 ± 5.7% vs 81.0 ± 4.2%, p = .03). A3 threshold was significantly lower in Group 2 (5.9 ± 0.7 m/s2, p < .05 vs 2.3 ± 0.5 m/s2, p < .05). CONCLUSION: Our novel sensing method might be a more feasible sensing method for obtaining higher AV synchrony than the conventional algorithm.

A case of cardiac sarcoidosis mimicking acute phase of takotsubo cardiomyopathy evaluated by multimodality cardiac imaging.

The patient was a 68-year-old woman who experienced loss of consciousness owing to a seizure while walking and bruised her face. Twelve­lead electrocardiography displayed a complete atrioventricular block. Transthoracic echocardiography displayed hypokinesis from the middle to apex of the myocardium. Emergency coronary angiography displayed no clear stenosis of the coronary arteries, and left ventriculography displayed takotsubo-like abnormal left ventricular wall motion. 99mTc-sestamibi/123I-beta-methyl iodophenyl pentadecanoic acid dual single-photon emission computed tomography displayed a perfusion/metabolism mismatch in the left apex, anterior segment, and inferior segment of the myocardium in the acute phase, which improved in the chronic phase. Similar mismatch findings were observed in the ventricular septum, which persisted in the chronic phase. Blood biomarkers of sarcoidosis were positive. Myocardial delayed enhancement was observed in the mid layer of the basal septum and inferior wall on cardiac magnetic resonance imaging. Fluorodeoxyglucose-positron emission tomography displayed signal accumulation in the basal septum. The clinical course of the patient suggested the possibility of cardiac sarcoidosis combined with takotsubo cardiomyopathy. This is a valuable case in which changes over time were detected by multimodality cardiac imaging. Learning objective: Cardiac manifestations of both takotsubo cardiomyopathy and sarcoidosis are similar, with both causing abnormal left ventricular wall motion. The co-occurrence of these conditions has been seldomly reported to date. The similarity of the characteristics of each condition poses a challenge in the diagnostic process. The utilization of multimodality cardiac imaging techniques, as demonstrated in the present case, is an effective means of establishing a diagnosis.

Diagnostic performance of pressure-bounded coronary flow reserve.

Fluid dynamics studies have proposed that coronary flow reserve can be calculated from coronary artery pressure instead of coronary blood flow. We sought to investigate the diagnostic performance of pressure-bounded coronary flow reserve (pb-CFR) compared with CFR measured by conventional thermodilution method (CFRthermo) in the clinical setting. Pressure guidewire was used to measure CFRthermo and fractional flow reserve (FFR) in left anterior descending coronary artery in 62 patients with stable coronary artery disease. Pb-CFR was calculated only with resting distal coronary artery pressure (Pd), resting aortic pressure (Pa) and FFR. Pb-CFR was moderately correlated with CFRthermo (r = 0.54, P < 0.001). Pb-CFR showed a poor agreement with CFRthermo, presenting large values of mean difference and root mean square deviation (1.5 ± 1.4). Pb-CFR < 2.0 predicted CFRthermo < 2.0 with an accuracy of 79%, sensitivity of 83%, specificity of 78%, positive predictive value of 48%, negative predictive value of 95%. The discordance presenting CFRthermo < 2.0 and pb-CFR ≥ 2.0 was associated with diffuse disease (P < 0.001). The discordance presenting CFRthermo ≥ 2 and pb-CFR < 2 was associated with a high FFR (P = 0.002). Pb-CFR showed moderate correlation and poor agreement with CFRthermo. Pb-CFR might be reliable in excluding epicardial coronary artery disease and microcirculatory disorders.

Central Systolic Blood Pressure as a Risk Factor for Accelerated Progression of Arterial Stiffness.

AIMS: In the arterial tree, a pressure gradient of the systolic blood pressure (SBP) is observed from the center to the periphery, with the pressure being higher in the periphery because of pressure wave reflection. However, this gradient is attenuated, with elevation of the central SBP (cSBP), in cases with abnormal pressure wave reflection in the arterial tree. It remains unclear if increase of the cSBP might be an independent risk factor for accelerated progression of arterial stiffness. We conducted this prospective observational study using latent growth curve model (LGCM) analyses to examine if elevated cSBP might be an independent risk factor for accelerated progression of the arterial stiffness in middle-aged Japanese men. METHODS: In this 9-year prospective observational study, we analyzed the data of 3862 middle-aged Japanese men (43±10years old) without cerebrocardiovascular disease at the study baseline who had undergone repeated annual measurements of the brachial-ankle pulse wave velocity (baPWV) and cSBP, as represented by the second peak of the radial pressure waveform (SBP2) in radial pressure waveform analysis. RESULTS: During the follow-up period (6.3±2.5years), significant increases of both the baPWV and SBP2 were observed in all the subjects. Analysis using the LGCM confirmed that the SBP2, a marker of the cSBP (B=0.260, P＜0.001), was a significant determinant of the slope of the annual changes of the baPWV during the study period. CONCLUSIONS: Our finding may appear to confirm elevated cSBP as an independent risk factor for accelerated progression of the arterial stiffness in middle-aged Japanese men.

Second Micra leadless pacemaker implantation by using intracardiac echocardiography.

The strategy after battery depletion was not established in Micra leadless pacemaker system (Micra). There are still some concerns in the 2nd Micra implantation, such as the mechanical interaction between both devices. The position of the 2nd Micra should be placed apart from the 1st Micra. We present a case of 1st Micra battery depletion who successfully underwent the 2nd Micra implantation under the intracardiac echo guidance. In our case, intracardiac echo was a very effective tool for confirming the location of Micra implantation.

Nutritional Status and Sleep Quality Are Associated with Atrial Fibrillation in Patients with Obstructive Sleep Apnea: Results from Tokyo Sleep Heart Study.

The prevalence of obstructive sleep apnea (OSA) in patients with atrial fibrillation (AF) has been observed to be much higher than in control participants without AF. Limited data exist regarding the prevalence of AF in patients with OSA. The clinical characteristics, nutritional status, and sleep parameters associated with AF in patients with OSA remain unclear. In this study, we aimed to determine the prevalence and factors associated with AF in patients with OSA from a large Japanese sleep cohort (Tokyo Sleep Heart Study). This was a single-center explorative cross-sectional study. Between November 2004 and June 2018, we consecutively recruited 2569 patients with OSA who underwent an overnight full polysomnography at our hospital. They were assessed using a 12-lead ECG and echocardiography. The clinical characteristics, sleep parameters, and medical history were also determined. Of the OSA patients, 169 (6.6%) had AF. Compared with the non-AF patients, OSA patients with AF were older and male, and they had higher prevalence of a history of alcohol consumption, hypertension, chronic kidney disease, and undernutrition, as well as a reduced ejection fraction. With regard to the sleep study parameters, OSA patients with AF had reduced slow-wave sleep and sleep efficiency, as well as higher periodic limb movements. There were no significant differences in the apnea-hypopnea index or hypoxia index between the two groups. The logistic regression analysis demonstrated that age (OR = 4.020; 95% CI: 1.895-8.527; p < 0.001), a history of alcohol consumption (OR = 2.718; 95% CI: 1.461-5.057; p = 0.002), a high CONUT score (OR = 2.129; 95% CI: 1.077-4.209; p = 0.030), and reduced slow-wave sleep (OR = 5.361; 95% CI: 1.505-19.104; p = 0.010) were factors significantly related to AF. The prevalence of AF in patients with OSA was 6.6%. Age, a history of alcohol consumption, undernutrition, and reduced sleep quality were independent risk factors for the presence of AF in patients with OSA, regardless of the severity of OSA.

Case report: successful termination of ventricular tachycardia by intrinsic anti-tachycardia pacing beyond conventional anti-tachycardia pacing.

Background: Anti-tachycardia pacing (ATP) is a pain-free alternative to defibrillation shock for monomorphic ventricular tachycardia (VT). Intrinsic ATP (iATP) is a novel algorithm of auto-programmed ATP. However, the advantage of iATP over conventional ATP in clinical cases is still unknown. Case summary: A 49-year-old man with no significant past medical history was transferred to our institution with sudden-onset fatigue from working on a farm. A 12-lead electrocardiogram showed monomorphic sustained wide QRS tachycardia with a right bundle branch block pattern and superior axis deviation with a cycle length (CL) of 300 ms. Sustained monomorphic VT originating from the left ventricle due to underlying vasospastic angina was diagnosed by contrast-enhanced cardiac magnetic resonance imaging, coronary angiography, and the acetylcholine stress test, and implantable cardioverter defibrillator implantation was performed. Nine months later, a clinical VT episode with a CL of 300 ms was observed, which could not be terminated by three sequences of conventional burst pacing. Ventricular tachycardia was finally terminated by a third iATP sequence without any acceleration. Discussion: Although standard burst pacing by conventional ATP reached the VT circuit, it failed to terminate the VT. Using the post-pacing interval, iATP automatically calculated the appropriate number of S1 pulses required to reach the VT circuit. In iATP, the S2 pulses are delivered with a calculated coupling interval based on the estimated effective refractory period during tachycardia. In this case, iATP might have led to less aggressive S1 stimulation, followed by aggressive S2 stimulation, which probably helped terminate the VT without any acceleration.

A case of short-coupled variant of Torsade de Pointes with bystander early repolarization in inferior leads.

The presence of J waves in cases of ventricular fibrillation (VF) is known to be a risk for sudden cardiac death. Recently, the effectiveness of radiofrequency catheter ablation (RFCA) for early repolarization syndrome (ERS) has been reported.The patient is a 30-year-old male with elevated J waves of 0.1 mV in the inferior leads, who had previously developed VF and undergone implantable cardioverter defibrillator (ICD) implantation. Because the VF from short coupled premature ventricular contraction (PVC) was presented, the RFCA of the triggered PVC was attempted. But it was unsuccessful due to no inducibility of the triggered PVC. After that, despite anti-arrythmia drug treatment, appropriate ICD shock for VF was observed. Although we decided to do a second ablation and evaluated epicardial arrhythmia substrate, no specific findings of early repolarization syndrome were found in the electrophysiological study. Finally, we considered that the cause of VF was short-coupled variant of Torsade de Pointes, and PVC ablation was performed. VF has not occurred since. We consider that this is a rare case to evaluate the epicardial arrhythmogenic substrate of J wave. Learning objective: Ablation of the epicardial arrhythmogenic substrate in patients with early repolarization syndrome (ERS) has been shown to be effective, but the relationship between abnormal epicardial potentials and the pathophysiology is unclear. In this case, J-wave and epicardial delayed potentials were not considered to represent obvious arrhythmogenic substrates. Ablation of the triggered premature ventricular contraction may be effective in ERS without apparent abnormal potentials.

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.

Initial multicenter clinical experience with the first-generation endoscopic guided laser balloon in Japan.

BACKGROUND: Isolation of the pulmonary veins (PVs) is the golden standard for atrial fibrillation (AF) ablation. To achieve a permanent PV isolation, the endoscopic guided HeartLight laser balloon system was invented. We analyzed the safety and efficacy of this laser balloon system. METHODS AND RESULTS: Three hundred four patients from 21 investigational sites inside Japan were enrolled in this study. One thousand sixty-two out of 1175 PVs (90.4%) were isolated using the HeartLight laser balloon. The isolation rate of the left superior, left inferior, right superior, and right inferior PVs was 87.8%, 91.3%, 91.6%, and 92.1%, respectively. The procedure time, defined as the time from the venous access to taking out the balloon, was 155 ± 39 min. The fluoroscopic time was 44 ± 25 min. The mean follow-up period was 309 ± 125 days. The freedom from AF recurrence at 3 months was 89.0% and at 12 months 82.1%. Adverse events occurred in 22 patients (7.2%) including phrenic nerve injury lasting more than 3 months in 1.6% and strokes in 1.0% of the patients. CONCLUSIONS: This initial experience demonstrated that the laser balloon ablation was feasible for PV isolation in Japanese AF patients.

Effect of Catheter Ablation for Atrial Fibrillation in Heart Failure With Mid-Range or Preserved Ejection Fraction　- Pooled Analysis of the AF Frontier Ablation Registry and Hokuriku-Plus AF Registry.

BACKGROUND: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group. CONCLUSIONS: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Ventricular fibrillation immediately after the treatment of Graves' disease coexisting with atypical angina and long QT syndrome: a case report.

BACKGROUND: Palpitations due to Graves' disease are often caused by supraventricular arrhythmia. However, in rare cases, the background of coronary artery disease, genetic abnormalities, or channel abnormalities can cause ventricular fibrillation, which is a lethal arrhythmia. Here, we report a case of ventricular fibrillation after administration of beta-blockers early in the course of treatment for Graves' disease coexisting with atypical angina and long QT syndrome. CASE PRESENTATION: A 48-year-old man consulted a local general physician for chest discomfort and palpitations for approximately 2 weeks. He was diagnosed with Graves' disease and treated with thiamazole 15 mg, bisoprolol 1.25 mg, and nitroglycerin 0.3 mg. The patient continued to experience chest discomfort the next day and visited our hospital. The patient was treated with landiolol 0.125 mg/kg/min for heart rate control, and 20 min later, electrocardiography showed a change from the R-on-T phenomenon to ventricular fibrillation. After cardiopulmonary resumption and improvement of thyroid function, a stress test was performed, which revealed coronary angina and long QT syndrome. An implantable cardioverter defibrillator (ICD) was implanted in the patient for secondary prevention. Since then, no fatal arrhythmia has been observed to date. CONCLUSIONS: When beta-blockers are administered to patients with Graves' disease who have severe chest symptoms, fatal arrhythmias are possible. ICD implantation should be considered for the secondary prevention of fatal arrhythmias.

Efficacy of left atrial posterior wall isolation guided by lesion size prediction module for non-paroxysmal atrial fibrillation.

AIMS: The efficacy of left atrial posterior wall isolation (PWI) is controversial. Lesion durability may be a major cause of arrhythmia recurrence. The use of the lesion size prediction module improves lesion durability. This study aimed to compare the clinical outcomes of pulmonary vein isolation (PVI) alone and PWI in addition to PVI (PVI + PWI) in patients with non-paroxysmal atrial fibrillation (AF) using a lesion size prediction module. METHODS AND RESULTS: This study is a sub-analysis of the recently published prospective multicentre observational study called ALCOHOL-AF (association of alcohol consumption with outcome of catheter ablation of AF). In this sub-analysis, patients with non-paroxysmal AF in whom PVI alone or PVI + PWI was performed using the lesion size prediction module were included. Freedom from atrial tachyarrhythmia was compared between PVI alone and PVI + PWI groups using propensity score analyses. Of the 3474 patients registered in the ALCOHOL-AF study, 572 patients (age 65.6 ± 10.1 years, male 77.4%, longstanding persistent AF 25.5%) were included in this sub-analysis. We selected 212 patients treated with PVI alone and 212 treated with PVI + PWI using one-to-one propensity score matching. During the follow-up period, atrial tachyarrhythmia recurrence was documented in 92 (43.4%) and 50 (23.6%) patients in the PVI alone and PVI + PWI groups, respectively. Freedom from atrial tachyarrhythmia recurrence without anti-arrhythmic drugs after a single procedure was significantly higher in PVI + PWI than in PVI alone groups (hazard ratio: 0.452, 95% confidence interval: 0.308-0.664, P < 0.001). CONCLUSION: In this hypothesis-generating study, lesion size prediction module-guided PVI + PWI was associated with better clinical outcomes than PVI alone in patients with persistent or longstanding persistent AF.

First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized Trial.

BACKGROUND: Catheter ablation as first-line therapy for ventricular tachycardia (VT) at the time of implantable cardioverter defibrillator (ICD) implantation has not been adopted into clinical guidelines. Also, there is an unmet clinical need to prospectively examine the role of VT ablation in patients with nonischemic cardiomyopathy, an increasingly prevalent population that is referred for advanced therapies globally. METHODS: We conducted an international, multicenter, randomized controlled trial enrolling 180 patients with cardiomyopathy and monomorphic VT with an indication for ICD implantation to assess the role of early, first-line ablation therapy. A total of 121 patients were randomly assigned (1:1) to ablation plus an ICD versus conventional medical therapy plus an ICD. Patients who refused ICD (n=47) were followed in a prospective registry after stand-alone ablation treatment. The primary outcome was a composite end point of VT recurrence, cardiovascular hospitalization, or death. RESULTS: Randomly assigned patients had a mean age of 55 years (interquartile range, 46-64) and left ventricular ejection fraction of 40% (interquartile range, 30%-49%); 81% were male. The underlying heart disease was ischemic cardiomyopathy in 35%, nonischemic cardiomyopathy in 30%, and arrhythmogenic cardiomyopathy in 35%. Ablation was performed a median of 2 days before ICD implantation (interquartile range, 5 days before to 14 days after). At 31 months, the primary outcome occurred in 49.3% of the ablation group and 65.5% in the control group (hazard ratio, 0.58 [95% CI, 0.35-0.96]; P=0.04). The observed difference was driven by a reduction in VT recurrence in the ablation arm (hazard ratio, 0.51 [95%CI, 0.29-0.90]; P=0.02). A statistically significant reduction in both ICD shocks (10.0% versus 24.6%; P=0.03) and antitachycardia pacing (16.2% versus 32.8%; P=0.04) was observed in patients who underwent ablation compared with control. No differences in cardiovascular hospitalization (32.0% versus. 33.7%; hazard ratio, 0.82 [95% CI, 0.43-1.56]; P=0.55) or mortality (8.9% versus 8.8%; hazard ratio, 1.40 [95% CI, 0.38-5.22]; P=0.62]) were observed. Ablation-related complications occurred in 8.3% of patients. CONCLUSIONS: Among patients with cardiomyopathy of varied causes, early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death. These findings were driven by a reduction in ICD therapies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02848781.