Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53 Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-Btype natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.

Aims The role of necroptosis in dilated cardiomyopathy (DCM) remains unclear. Here, we examined whether phosphorylation of mixed lineage kinase domain‐like protein (MLKL), an indispensable event for execution of necroptosis, is associated with the progression of DCM. Methods and results Patients with DCM (n = 56, 56 ± 15 years of age; 68% male) were enrolled for immunohistochemical analyses of biopsies. Adverse events were defined as a composite of death or admission for heart failure or ventricular arrhythmia. Compared with the normal myocardium, increased signals of MLKL phosphorylation were detected in the nuclei, cytoplasm, and intercalated discs of cardiomyocytes in biopsy samples from DCM patients. The phosphorylated MLKL (p‐MLKL) signal was increased in enlarged nuclei or nuclei with bizarre shapes in hypertrophied cardiomyocytes. Nuclear p‐MLKL level was correlated negatively with septal peak myocardial velocity during early diastole (r = −0.327, P = 0.019) and was correlated positively with tricuspid regurgitation pressure gradient (r = 0.339, P = 0.023), while p‐MLKL level in intercalated discs was negatively correlated with mean left ventricular wall thickness (r = −0.360, P = 0.014). During a median follow‐up period of 3.5 years, 10 patients (18%) had adverse events. To examine the difference in event rates according to p‐MLKL expression levels, patients were divided into two groups by using the median value of nuclear p‐MLKL or intercalated disc p‐MLKL. A group with high nuclear p‐MLKL level (H‐nucMLKL group) had a higher adverse event rate than did a group with low nuclear p‐MLKL level (L‐nucMLKL group) (32% vs. 4%, P = 0.012), and Kaplan–Meier survival curves showed that the adverse event‐free survival rate was lower in the H‐nucMLKL group than in the L‐nucMLKL group (P = 0.019 by the log‐rank test). Such differences were not detected between groups divided by a median value of intercalated disc p‐MLKL. In δ‐sarcoglycan‐deficient (Sgcd−/−) mice, a model of DCM, total p‐MLKL and nuclear p‐MLKL levels were higher than in wild‐type mice. Conclusion The results suggest that increased localization of nuclear p‐MLKL in cardiomyocytes is associated with left ventricular diastolic dysfunction and future adverse events in DCM.

Methods SubjectsThis study was a single-center retrospective study conducted at Sapporo Medical University Hospital. The subjects consisted of 247 consecutive patients with drug-refractory and symptomatic AF who underwent first-time radiofrequency (RF) CA at the present institute between 2011 and 2016. One patient in whom PVI could not be successfully achieved and 19 patients who did not have 4 PV (e.g., a prominent left common PV and a previous history of surgery for lung cancer), were excluded from this study. Thus, 227 patients (908 PV) contributed to data analysis regarding exit block. Of the 227 patients, 49 had AF recurrence and proceeded to the second session, but 1 patient did not have evaluation of exit block. Paroxysmal AF (PAF) was diagnosed when AF terminated in ≤7 days and both AF and sinus rhythm (SR) had been documented on 12-lead electrocardiography (ECG) and/or Holter monitoring. Non-PAF was defined as continuous AF persisting for >7 days. 5 Catheter AblationAnti-arrhythmic agents were discontinued on admission (i.e., 2 days before CA). 3-D reconstructed computed P ulmonary vein isolation (PVI) has been established as an essential and standard approach in catheter ablation (CA) for atrial fibrillation (AF). Despite recent improvement in CA technology, AF recurs at a significantly high rate after successful PVI. 1,2 Spontaneous electrical activity originating from the myocardial sleeve at the ostium of the pulmonary vein (PV) and/or antrum of the left atrium (LA) is known to be a major trigger source of AF. 3 Therefore, the primary goal of PVI is complete electrical isolation of the PV from the LA, given that electrical reconnection between them plays an important role in the recurrence of AF. 1,4 Guidelines recommend confirmation of the presence of entrance block (LA to PV; class I indication) at least, and of exit block (PV to LA) if possible (class IIb) to ensure completion of electrical isolation when performing PVI, 5 but it is not always possible to demonstrate exit block after PVI, and the question of whether non-demonstrable exit block is associated with an increased risk of PV reconnection after PVI has not been clarified. The purpose of this study was therefore to clarify the prevalence and significance of exit block in the context of PVI and its association with long-term PV reconnection, which is responsible for the recurrence of AF.Background: Demonstration of exit block from the pulmonary vein (PV) to the left atrium after PV isolation (PVI) is not always possible after demonstration of entrance block. We examined factors associated with demonstrable exit block and the relationship between demonstrable exit block and subsequent PV reconnection.

Background Catheter ablation is an effective treatment for atrial fibrillation (AF), but it carries risk of perioperative thromboembolism even in cases with low CHADS2 scores. Here, we examined whether a combination of clinical variables can predict stroke risk factors that are assessed by transesophageal echocardiography (TEE). Methods The study population consisted of 209 consecutive AF patients with a CHADS2 score of 0 or 1 (58.7 ± 10.6 years old; persistent AF, 33.0%). All patients underwent TEE, and TEE‐determined stroke risk (TEE risk) was defined as cardiac thrombus/sludge, dense spontaneous echo contrast (SEC), and/or peak left atrial appendage (LAA) flow velocity <0.25 m/s. Results Transesophageal echocardiography risk was observed in 10.5% of the patients. In multivariate logistic analysis, persistent AF [odds ratio (OR): 11.5, CI: 3.14‐42.1, P = .0002], left atrial diameter (LAD) (OR: 1.10, CI: 1.01‐1.20, P = .0293), contrast medium defect (CMD) in the LAA detected by computed tomography (OR: 20.2, CI: 6.3‐65.0, P < .0001), and serum brain natriuretic peptide (BNP) level (OR: 1.00, CI: 1.00‐1.01, P = .0056) were independent predictors of TEE risk. A new scoring system comprising LAD > 41 mm (1 point), BNP > 47 pg/mL (1 point), CMD (2 points), and persistent AF (2 points) was constructed and defined as TEE‐risk score. The area under the curve (AUC) for prediction of TEE risk was 0.631 in modified CHADS2 score and it was 0.852 in TEE‐risk score. Conclusion Transesophageal echocardiography risk is predictable by TEE‐risk score, and its combination with CHADS2 score may improve the stroke risk stratification in AF patients with a low CHADS2 score.

Background Earlier studies have shown male dominance of an early repolarization (ER) pattern and frequent coexistence with high Sokolow‐Lyon voltage. Although possible involvement of androgen is speculated, the underlying mechanism has not been clarified yet. Previous studies were conducted in adult populations or only in children, and there has been no study in which the ER pattern was investigated in a series of individuals ranging from children before puberty to adults. Methods We included 600 individuals comprising six groups according to age: 10–14 years old, 15–19 years old, twenties, thirties, forties, and fifties. Each group had 50 males and 50 females. The distribution of an ER pattern and related ECG parameters were assessed by age and gender. Results In early teenagers, there was no significant gender difference in the prevalence of an ER pattern (24% in men vs. 28% in women, p = .82). The prevalence of an ER pattern increased after puberty and reached a peak in men in their twenties (42%). With further advance of age, the prevalence of an ER pattern decreased. On the other hand, the prevalence of an ER pattern in women peaked at 28% in teenagers, and it decreased through twenties (20%) to thirties (10%). Similar male dominance after puberty was observed in Sokolow‐Lyon voltage and J‐point elevation but not in P‐wave amplitude. Conclusion The prevalence of an ER pattern, Sokolow‐Lyon voltage, and J‐point elevation are all augmented after puberty and decrease with aging, leading to frequent coexistence of these ECG findings in young men.